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hemostaseimmunologieintensieve-zorg

2024

APRIL

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Lower-Dose Emicizumab Prophylaxis: Can Less Be More?

The shifting paradigm in hemophilia prophylaxis of targeting higher than 1% trough levels starting about a decade ago with extended halflife (EHL) clotting factor concentrates (CFCs) producing much better hemostatic outcomes, got a boost with the advent of the first non-clotting factor hemostatic product, emicizumab, a factor VIII mimetic, which was introduced in clinical practice about 5 years ago.

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Innovative Therapies for Acquired Hemophilia A

Acquired hemophilia A (AHA) is a rare autoimmune bleeding disorder which can be life-threatening. AHA is due to autoantibodies against coagulation factor VIII.

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100 Years of Thrombotic Thrombocytopenic Purpura: A Story of Death and Life

One hundred years ago, in 1924, the first description of a patient with a disease, now known as thrombotic thrombocytopenic purpura (TTP) was published by Dr. Eli Moschcowitz.

A Global Analysis of The Use of Immunoglobulin, Shortages in Supply, and Mitigating Measures: A Survey of Hospital Providers (a BEST Collaborative Study)

Immunoglobulin (IG) therapy is widely used to treat primary and secondary immune deficiencies and as immunomodulatory agent for various disorders. There is great concern that shortages of IG may rise, potentially affecting medical treatment options.

The BIG Question: Can We Stop the Use of HBIG?

Hemophilia is a genetic disorder that is caused by mutations in coagulation factor VIII (hemophilia A) or IX (hemophilia B) genes resulting in blood clotting disorders.

Pregnancy in Myasthenia Gravis: A Retrospective Analysis of Maternal and Neonatal Outcome from a Large Tertiary Care Centre in Germany

Myasthenia gravis (MG) is a rare, potentially life-threatening autoimmune disease with fluctuating muscle weakness frequently affecting women of childbearing age. MG can affect maternal as well as neonatal outcome with risk of worsening of myasthenic symptoms in the mothers and risk of transient neonatal myasthenia gravis (TNMG) and arthrogryposis multiplex congenita (AMC) or foetal acetylcholine receptor antibody-associated disorders (FARAD) in the neonates.

Guideline for Laboratory Diagnosis and Monitoring of von Willebrand Disease: A Joint Guideline from the United Kingdom Haemophilia Centre Doctors&Apos; Organisation and The British Society for Haematology

This guideline updates the previous guidelines published on behalf of the British Society for Haematology (BSH) and the United Kingdom Haemophilia Centre Doctors' Organization (UKHCDO), focusing on the laboratory components of diagnosis and monitoring.

Haemophilia in the Era of Novel Therapies: Where Do Inhibitors Feature in the New Landscape?

The advent of therapeutic recombinant factor VIII (FVIII) and factor IX (FIX) protein infusions revolutionized the care of persons with haemophilia in the 1990s. It kicked off an era with the increasing use of prophylactic factor infusions for patients and transformed conversations around the ideal trough activity levels as well as the ultimate goals in tailored, individualized care.

Challenges in Ageing Persons with Haemophilia

As treatments for individuals with inherited bleeding disorders improve, life expectancy increases and is approaching that of the normal population. Concomitant with this we are now seeing the problems of ageing in the bleeding disorder population.

Women and Girls with Inherited Bleeding Disorders: Focus on Haemophilia Carriers and Heavy Menstrual Bleeding

Raising awareness and improving recognition, accurate classification, and enhanced access to new treatments represent current key challenges for carriers of haemophilia. Women and girls carrying genes for haemophilia often experience significant bleeding and/or low factor levels.

Clinical and Treatment Characteristics of Infants and Toddlers Less Than Two Years of Age with Hemophilia

Infants and toddlers (ITs) with hemophilia have unique bleeding features. Factor prophylaxis has been shown to decrease the risk of intracranial hemorrhage (ICH), which supports recommendations to begin at a young age.

An Evolving Understanding of Low VWF and Type 1 VWD

In this issue of Blood1 Atiq et al present data to support the hypothesis that low von Willebrand factor (VWF) is an age-dependent evolution of type 1 von Willebrand disease (VWD) rather than its own discrete clinical entity.

How Much Prophylaxis Is Enough in Haemophilia?

Prophylaxis has become standard of care for all persons with haemophilia (PWH) with a severe phenotype. However, 'standard prophylaxis' with either factor or non-factor therapies (currently only emicizumab available) is prohibitively expensive for much of the world. We sought to address the question of 'How much prophylaxis is enough?' and 'Can it be individualized?' and specifically 'Can emicizumab be individualized?'.

Classification of Recombinant Factor VIII Products and Implications for Clinical Practice: A Systematic Literature Review

Consensus over the definition of recombinant factor VIII (rFVIII) product classification in haemophilia A is lacking. rFVIII products are often classified as standard half-life (SHL) or extended half-life (EHL); despite this, no universally accepted definition currently exists.

2024

MAART

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Comprehensive Analysis of the Role of Fibrinogen and Thrombin in Clot Formation and Structure for Plasma and Purified Fibrinogen

Altered properties of fibrin clots have been associated with bleeding and thrombotic disorders, including hemophilia or trauma and heart attack or stroke. Clotting factors, such as thrombin and tissue factor, or blood plasma proteins, such as fibrinogen, play critical roles in fibrin network polymerization.

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Post-Reconstitution Hemostatic Stability Profiles of Canadian and German Freeze-Dried Plasma

Despite the importance of the hemostatic properties of reconstituted freeze-dried plasma (FDP) for trauma resuscitation, few studies have been conducted to determine its post-reconstitution hemostatic stability. This study aimed to assess the short- (≤24 h) and long-term (≥168 h) hemostatic stabilities of Canadian and German freeze-dried plasma (CFDP and LyoPlas) after reconstitution and storage under different conditions.

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The History of Extracorporeal Membrane Oxygenation and the Development of Extracorporeal Membrane Oxygenation Anticoagulation

Extracorporeal membrane oxygenation (ECMO) was first started for humans in early 1970s by Robert Bartlett. Since its inception, there have been numerous challenges with extracorporeal circulation, such as coagulation and platelet activation, followed by consumption of coagulation factors and platelets, and biocompatibility of tubing, pump, and oxygenator.

Challenges in the Early Diagnosis and Treatment of Chronic Inflammatory Demyelinating Polyradiculoneuropathy in Adults: Current Perspectives

Diagnosing Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) poses numerous challenges. The heterogeneous presentations of CIDP variants, its mimics, and the complexity of interpreting electrodiagnostic criteria are just a few of the many reasons for misdiagnoses.

Acquired hemophilia A: a single-center study of 165 patients

Acquired hemophilia A (AHA) is a rare hemorrhagic disorder caused by factor (F)VIII inhibitors. The diagnosis and management of AHA remains challenging because of its rarity and heterogeneity.

Pharmacokinetic-Pharmacodynamic Modelling in Hemophilia A: Relating Thrombin and Plasmin Generation to Factor VIII Activity After Administration of a VWF/FVIII Concentrate

Hemophilia A patients are treated with factor (F) VIII prophylactically to prevent bleeding. In general, dosage and frequency are based on pharmacokinetic measurements. Ideally, an alternative dose adjustment can be based on the hemostatic potential, measured with a thrombin generation assay (TGA), like the Nijmegen hemostasis assay.

An observational study of haemophilia A patients without inhibitors using the French national claims (SNDS) database

OBJECTIVES: To describe clinical characteristics, factor consumption, and events of interest in patients with haemophilia A without inhibitors receiving prophylaxis in France, and the clinical impact of switching to Elocta® in this population.

Genetic Landscape of Factor VII Deficiency: Insights from a Comprehensive Analysis of Pathogenic Variants and Their Impact on Coagulation Activity

Congenital factor VII (FVII) deficiency is a rare genetic bleeding disorder characterized by deficient or reduced activity of coagulation FVII. It is caused by genetic variants in the F7 gene.

The spectrum of neutralizing and non-neutralizing anti-FVIII antibodies in a nationwide cohort of 788 persons with hemophilia

Anti-factor VIII (FVIII) antibodies have been reported to exhibit both neutralizing and non-neutralizing characteristics. This is the first study investigating the full spectrum of FVIII-specific antibodies, including non-neutralizing antibodies, very-low titer inhibitors, and inhibitors, in a large nationwide population of persons with hemophilia A of all severities.

Bleeding Disorder of Unknown Cause: A Diagnosis of Exclusion

Patients with an unexplained mild to moderate bleeding tendency are diagnosed with bleeding disorder of unknown cause (BDUC), a classification reached after ruling out other mild to moderate bleeding disorders (MBD) including von Willebrand disease (VWD), platelet function defects (PFDs), coagulation factor deficiencies (CFDs), and non-hemostatic causes for bleeding.

Rare variants in alpha 1 antitrypsin deficiency: a systematic literature review

Alpha 1 Antitrypsin Deficiency (AATD) is a largely underrecognized genetic condition characterized by low Alpha 1 Antitrypsin (AAT) serum levels, resulting from variations in SERPINA1. Many individuals affected by AATD are thought to be undiagnosed, leading to poor patient outcomes.

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Massive Transfusion in Trauma

The purpose of this review is to provide an overview of currently recommended treatment approaches for traumatic hemorrhage shock, with a special focus on massive transfusion.

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Analyzing and Modeling Massive Transfusion Strategies and The Role of Fibrinogen-How Much Is the Patient Actually Receiving?

Hemorrhage is a leading cause of preventable death in trauma, cardiac surgery, liver transplant, and childbirth. While emphasis on protocolization and ratio of blood product transfusion improves ability to treat hemorrhage rapidly, tools to facilitate understanding of the overall content of a specific transfusion strategy are lacking.

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Guidelines in Trauma-Related Bleeding and Coagulopathy: An Update

PURPOSE OF REVIEW The diagnosis and treatment of patients with severe traumatic bleeding and subsequent trauma-induced coagulopathy (TIC) is still inconsistent, although the implementation of standardized algorithms/treatment pathways was repeatedly linked to improved outcome. Various evidence-based guidelines for these patients now exist, three of which have recently been updated.

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Management and Outcomes of Women with Low Fibrinogen Concentration During Pregnancy or Immediately Postpartum: A UK National Population-Based Cohort Study

Pregnant women with a fibrinogen level <2 g/L represent a high-risk group that is associated with severe postpartum hemorrhage and other complications. Women who would qualify for fibrinogen therapy are not yet identified.

Assessment of Rare Bleeding Disorders in Adolescents with Heavy Menstrual Bleeding

There are a significant number of patients with mucocutaneous bleeding, specifically heavy menstrual bleeding (HMB), who do not have a diagnosed bleeding disorder. These patients receive nontargeted interventions and may have suboptimal treatments.

The Concept of Thromboinflammation

Inflammation and thrombosis are intricate and closely interconnected biological processes that are not yet fully understood and lack effective targeted therapeutic approaches.

Immune Gene Polymorphisms Associated with Poor Response to Platelet Transfusion and Recombinant Factor VII Administration in Glanzmann Thrombasthenia

Poor response to platelet and recombinant factor VII administration is a major problem in patients with Glanzmann Thrombasthenia (GT). The risk factors associated with poor response to treatment in these patients are unknown. Some genetic variations of cytokines may contribute to therapy resistance.

Current Understanding of Immune Thrombocytopenia: A Review of Pathogenesis and Treatment Options

The management of immune thrombocytopenia (ITP) and the prediction of patient response to therapy still represent a significant and constant challenge in hematology. ITP is a heterogeneous disease with an unpredictable evolution.

Management and Follow-Up of Pregnancy-Onset Thrombotic Thrombocytopenic Purpura: The French Experience

Pregnancy-onset thrombotic thrombocytopenic purpura (TTP) is a rare and life-threatening disease of which diagnosis and management requires experienced multidisciplinary teams.

Real-World Treatment of Patients with Severe Congenital Protein C Deficiency with Protein C Concentrate: A Physician Survey

Replacement therapy with intravenous (IV) protein C concentrate is an approved treatment approach for patients with severe congenital protein C deficiency (SCPCD). Data on the real-world use of protein C concentrate are limited.

Diagnosis and Treatment of Von Willebrand Disease in 2024 and Beyond

The diagnosis and clinical care of patients with von Willebrand disease (VWD) has continued to evolve since the characterization of the von Willebrand factor (VWF) gene in 1985.

Rare Bleeding Disorders: Advances in Management

Inherited factor coagulation deficiencies and vascular bleeding disorders, associated with bleeding of various severity, are often classified as rare bleeding disorders (RBDs). These include inherited fibrinogen disorders, inherited platelet function disorders (IPFD) and hereditary haemorrhagic telangiectasia (HHT).

Use of Vonicog Alpha and Acquired Von Willebrand Syndrome, A New Approach: A Case Report

Therapeutic management of acquired von Willebrand syndrome (AVWS) can be challenging, particularly in cases of AVWS associated with monoclonal IgM such as Waldenström macroglobulinemia (WM) where several therapeutic options may be ineffective.

2024

JANUARI

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Controversies Regarding Albumin Therapy in Cirrhosis

Albumin is the most abundant protein in the human body and is synthetized exclusively by the liver. Therefore, serum albumin levels are reduced in acute and/or chronic liver disease. In cirrhosis, low levels of albumin predict the outcome.

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Management of Pregnancy and Delivery in Congenital Fibrinogen Disorders: Communication from the ISTH SSC Subcommittee on Factor XIII and Fibrinogen

Congenital fibrinogen disorders (CFDs) are a heterogeneous group of rare congenital quantitative and / or qualitative fibrinogen deficiency.

Impact of 2021 European Academy of Neurology/Peripheral Nerve Society Diagnostic Criteria on Diagnosis and Therapy of Chronic Inflammatory Demyelinating Polyradiculoneuropathy Variants

There are different criteria for the diagnosis of different variants of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). The 2021 European Academy of Neurology/Peripheral Nerve Society (EAN/PNS) guidelines provide specific clinical criteria for each CIDP variant even if their therapeutical impact has not been investigated.

Myasthenia Gravis: The Changing Treatment Landscape in the Era of Molecular Therapies

Myasthenia gravis (MG) is an autoimmune disorder that affects the neuromuscular junction, leading to muscle weakness and fatigue. MG is caused by antibodies against the acetylcholine receptor (AChR), the muscle-specific kinase (MuSK) or other AChR-related proteins that are expressed in the postsynaptic muscle membrane.

Acquired Hemophilia A after Multiple Transfusions Following Trauma

Acquired hemophilia A (AHA) is a coagulative disorder that is caused by the presence of inhibitors of factor VIII (FVIII). The presence of coagulation factor inhibitors can lead to severe episodes of bleeding in patients with no previous history of bleeding conditions.

The Under-Evaluated Impacts of the Therapeutic Revolution of Hemophilia on Women and Girls

The advent of new treatment options over the last decades has markedly improved the lives of male persons with hemophilia (PwH).

Determinants of Bleeding Before and During Immune Tolerance in 222 Boys with Severe Hemophilia A and Inhibitors >5 BU

Prevention of bleeding and its consequences is the main goal of hemophilia treatment and determines treatment choices for patients who develop inhibitors. To assess bleeding before and during immune tolerance induction (ITI) and its association with ITI regimen and inhibitor titer, we selected and analyzed data on patients receiving high-titer inhibitors from the international prospective PedNet cohort study

The World Federation of Hemophilia World Bleeding Disorders Registry: Insights from the First 10,000 Patients

The prevalence of hemophilia varies globally, with close to 100% of patients diagnosed in high-income countries and as low as 12% diagnosed in lower -income countries. These inequalities in the care of people with hemophilia exist across various care indicators.

Hereditary Coagulation Factor XI Deficiency: A Rare or Neglected Disease? Results From a Retrospective, Single-Centre Cohort in Northern Italy

To examine real-life clinical data regarding hereditary factor XI (FXI) deficiency from a secondary care center. Retrospective review of clinical records for every FXI:C 0.7 IU/ml or less reported from 2012 to 2020.

Factor XI Deficiency: Phenotypic Age-Related Considerations and Clinical Approach Towards Bleeding Risk Assessment

Factor XI (FXI) deficiency is a rare bleeding disorder that presents complex challenges in patient assessment and bleeding risk management. Despite generally causing mild to moderate bleeding symptoms, clinical manifestations can vary, and bleeding tendency does not always correlate with FXI plasma levels or genotype.

Impact of Inherited Bleeding Disorders on Maternal Bleeding and Other Pregnancy Outcomes: A Population-Based Cohort Study

Increasing rate of postpartum haemorrhage (PPH) has been observed between 2003 and 2010 in Canada. Inherited bleeding disorders contribute to the risk of PPH. AIM: To identify the trend in PPH in the last decade, assess the impact of bleeding disorders on pregnancy outcomes and evaluate their coagulation workup during pregnancy.

Minimum Factor Viii Levels to Prevent Joint Bleeding in Mild Hemophilia A

The severity of the bleeding phenotype in patients with hemophilia A (HA) broadly correlates with the degree of coagulation factor VIII (FVIII) deficiency in plasma. However, the FVIII level necessary to achieve the goal of zero joint bleeds remains unclear. This study aimed to identify the minimum FVIII level necessary to prevent joint bleeds in patients with HA.

2023

DECEMBER

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Fibrinogen Early in Severe Trauma studY (FEISTY): results from an Australian multicenter randomized controlled pilot trial

Haemorrhage is a major cause of death in severe trauma. Fibrinogen plays a critical role in maintaining haemostasis in traumatic haemorrhage, and early replacement using fibrinogen concentrate (FC) or cryoprecipitate (Cryo) is recommended by several international trauma guidelines.

Acquired Hemophilia A: A Rare, Acquired Coagulopathy in the Postpartum Setting

Postpartum hemorrhage (PPH) remains a leading cause of maternal morbidity. Pregnancy-associated acquired hemophilia A (AHA) caused by autoantibodies against factor VIII can present with recurrent episodes of postpartum bleeding.

Key Drivers of Coagulation Factor Use in Von Willebrand Disease During Hospitalization: An Overview of the French BERHLINGO Cohort

Von Willebrand disease (VWD) is the most common inherited bleeding disorder. However, studies of hospitalization patterns with replacement treatment are scarce.

Association of patient, treatment, and disease characteristics with patient-reported outcomes: Results of the ECHO Registry

Patient-reported outcomes (PROs) in people living with haemophilia A (PLWHA) are often under-reported. Investigating PROs from a single study with a diverse population of PLWHA is valuable, irrespective of FVIII product or regimen.

The Year in Coagulation and Transfusion: Selected Highlights from 2022

This is an annual review to cover highlights in transfusion and coagulation in patients undergoing cardiovascular surgery.

von Willebrand factor: aging is better?

Aging is a process that gives rise to a number of metabolic, molecular, and anatomical changes that compromise established balances. The regulation of hemostatic equilibria is no exception to the rule, and aging is therefore considered a powerful risk factor for thrombosis.

Association between Clauss fibrinogen concentration and ROTEM® FIBTEM

Point-of-care tests like FIBTEM A5 have been proposed to guide the treatment of patients who might have low fibrinogen concentrations (≤2 g/L). The aim of this study was to describe fibrinogen concentrations according to previously proposed FIBTEM A5 cut-off points in blood samples collected from women during postpartum haemorrhage.

European pathways of care in Alpha-1 Antitrypsin deficiency

Despite initiatives to improve awareness and treatment of alpha-1 antitrypsin deficiency (AATD), country-level processes for AATD management remain unclear.

Treatment for Alpha-1 Antitrypsin Deficiency Does Augmentation Therapy Work?

Alpha-1 antitrypsin deficiency (AATD) is a rare inherited cause of chronic obstructive pulmonary disease that affects an estimated 250,000 individuals in Europe and North America.

Inhibitor development according to concentrate in severe hemophilia: reporting on 1392 Previously Untreated Patients from Europe and Canada

Clotting factor concentrates have been the mainstay of severe hemophilia treatment over the last 50 years. Differences in risk of neutralizing antibody (inhibitor) formation according to concentrate used remain clinically relevant.

2023

NOVEMBER

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Viscoelastic Testing Methods

Viscoelastic testing methods examine the real-time formation of a clot in a whole blood sample, and include thromboelastography (TEG), rotational thromboelastometry (ROTEM), and several other testing platforms.

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The Molecular Structure of Fibrinogen

Seminars in Thrombosis and Hemostasis (STH) celebrates 50 years of publishing in 2024. To celebrate this landmark event, STH is republishing some archival material. This manuscript represents the first full paper ever published in STH.

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International council for standardization in haematology recommendations on fibrinogen assays, thrombin clotting time and related tests in the investigation of bleeding disorders

This guidance was prepared on behalf of the International Council for Standardization in Haematology (ICSH) by an international working group of clinicians and scientists. The document focuses on tests and assays used for the assessment of fibrinogen function, particularly in the scenario of bleeding disorders.

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Prothrombin complex concentrate (PCC) for treatment of trauma-induced coagulopathy: systematic review and meta-analyses

Trauma-induced coagulopathy (TIC) is common in trauma patients with major hemorrhage. Prothrombin complex concentrate (PCC) is used as a potential treatment for the correction of TIC, but the efficacy, timing, and evidence to support its use in injured patients with hemorrhage are unclear.

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Early Goal-Directed Hemostatic Therapy for Severe Acute Bleeding Management in the Intensive Care Unit: A Narrative Review

This is a narrative review of the published evidence for bleeding management in critically ill patients in different clinical settings in the intensive care unit (ICU).

Efficacy of emicizumab is maintained throughout dosing intervals for bleed prophylaxis

Across the HAVEN clinical trial program, the efficacy of emicizumab has been demonstrated in children, adolescents, and adults with hemophilia A, with or without factor VIII inhibitors.

Innovations 2022 in Hemostasis and thrombosis: what’s new?

We summarize hereafter five topics that caught our attention in 2022, related to anticoagulants and hemophilia.

Von Willebrand Factor as a Biomarker for Liver Disease - An Update

The von Willebrand factor (vWF) is best known for its role in the hemostatic pathway, aiding platelet adhesion and aggregation, as well as circulating along with coagulation factor VIII, prolonging its half-life. However, vWF is more than a hemostatic protein and is a marker of endothelial dysfunction in patients with cirrhosis.

Prophylactic and therapeutic strategies for intraoperative bleeding in women with von Willebrand disease and heavy menstrual bleeding: A systematic review

Optimal peri-operative management for women with Von Willebrand disease (VWD) and heavy menstrual bleeding (HMB) remains undetermined.

2023

OKTOBER

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Preoperative fibrinogen level and blood transfusions in liver transplantation: A systematic review

Orthotopic liver transplantation (OLT) is a major surgery often associated with significant bleeding. We conducted a systematic review to explore the association between preoperative fibrinogen level and intraoperative blood products transfusion, blood loss and clinical outcomes in patients undergoing OLT.

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Fifty Years of Fibrinogen Structure and Function

Reissuing historical scientific papers from the Seminars in Thrombosis and Hemostasis “vault” or treasure trove to celebrate 50 years of publishing is a fantastic idea, bringing important original studies or reviews such as “The Molecular Structure of Fibrinogen” by Murano back into the light for new generations of scientists to discover them or more senior colleagues to rediscover.

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TRAUMA-INDUCED COAGULOPATHY: WHAT YOU NEED TO KNOW

Trauma-induced coagulopathy (TIC) is a global inflammatory state accompanied by coagulation derangements, acidemia, and hypothermia, that occurs after traumatic injury. It occurs in approximately 25% of severely injured patients, and its incidence is directly related to injury severity.

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Management of major bleeding for anticoagulated patients in the Emergency Department: an European experts consensus statement

An increasing number of patients presenting to the emergency department (ED) with life-threatening bleeding are using oral anticoagulants, such as warfarin, Factor IIa and Factor Xa inhibitors. Achieving rapid and controlled haemostasis is critically important to save the patient's life.

Efficacy and Safety of Intravenous Immunoglobulin Treatment in Selected Neurological Diseases—One Centre’s Experience Based on the Therapy of 141 Patients

Intravenous immunoglobulins (IVIg) are the first-choice drugs for the treatment of certain neuroimmune diseases. The aim of this study was to evaluate the efficacy and safety of IVIg in patients with selected nervous system diseases.

Low-dose intravenous immunoglobulin (IVIg) in different immune-mediated conditions

IVIg has been used for a long time as a replacement therapy for primary and secondary immunodeficiencies. Beside this supplementary role, when used at higher doses (i.e., 2 g/kg/monthly) it exerts an immunomodulatory role able to control multiple autoimmune and systemic inflammatory diseases.

Anti-Inflammatory and Immunomodulatory Effect of High-Dose Immunoglobulins in Children: From Approved Indications to Off-Label Use

The large-scale utilization of immunoglobulins in patients with inborn errors of immunity (IEIs) since 1952 prompted the discovery of their key role at high doses as immunomodulatory and anti-inflammatory therapy, in the treatment of IEI-related immune dysregulation disorders, according to labelled and off-label indications.

Coagulation factors II, V, VII, IX, X and XI and mortality - a cohort study

Elevated levels of coagulation factors (F) II (FII), FV, FVII, FIX, FX, and FXI have often been related with coronary heart disease, ischemic stroke, and venous thrombosis (VT). However, there are few studies on their associations with all-cause mortality.

Hemophilia gene therapy: first, do no harm

The introduction of adeno-associated virus-mediated, liver-directed gene therapy into the hemophilia treatment landscape brings not only great promise but also considerable uncertainty to a community that has a history punctuated by the devastating effects of HIV and hepatitis C virus.

Clinical and laboratory presentation and underlying mechanism in patients with low VWF

Low von Willebrand factor (VWF) refers to subjects with plasma levels of 30-50 IU/dL. The mechanism of low VWF is poorly understood. We chose to determine the clinical presentation, laboratory phenotype and underlying mechanisms of low VWF.

Acquired Hemophilia A: Bleeding Pattern and Hemostatic Therapeutic Strategies

Acquired Hemophilia A (AHA) is a rare autoimmune disorder characterized by the onset of a sudden and unexpected bleeding episode in a patient with no personal or family history of bleeding diathesis, and with a typical laboratory feature, i.e., a prolonged activated partial thromboplastin time that is not otherwise explained.

Targeting von Willebrand disease: the current status and future directions of management therapies

von Willebrand disease (VWD) is the commonest inherited bleeding disorder and is typically caused by deficits in the quantity or quality of von Willebrand factor (VWF).

Accreditation model of European Haemophilia Centers in the era of novel treatments and gene therapy

The international certification of haemophilia centers in Europe is run by the European Association of Haemophilia and Allied Disorders (EAHAD) and European Haemophilia Consortium (EHC) since 2013. The centers are designated as European Haemophilia Comprehensive Care Centers (EHCCC) or European Haemophilia Treatment Centers (EHTC), based on the specific requirements which evaluate centers’ ability to provide care for patients with haemophilia and allied disorders.

Eptacog beta efficacy and safety in underweight, normal weight, and overweight/obese persons with hemophilia A or B and inhibitors

Being overweight or obese increases the disease burden faced by persons with hemophilia, and the prevalence of these comorbidities in persons with hemophilia may be rising along with that of the general population.

2023

JUNI

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Real-World Experience with a Human Fibrinogen Concentrate: Clinical Data from Adult and Pediatric Patients Requiring Fibrinogen for Bleeding Control and Prevention

Human fibrinogen concentrate (Fibryga®, Octapharma AG) received temporary approval for fibrinogen replacement therapy in France (2017), subsequently obtaining full approval for congenital and acquired hypofibrinogenemia.

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Interventions of Postpartum Hemorrhage

Postpartum hemorrhage is a common and potentially life-threatening obstetric complication, with successful management relying heavily on early identification of hemorrhage and prompt intervention.

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Association Between Plasma Fibrinogen Concentration After Cardiopulmonary Bypass and Postoperative Blood Loss in Children Undergoing Cardiac Surgery: A Retrospective Cohort Study

Intraoperative hypofibrinogenemia is a major factor associated with increased postoperative blood loss in adult cardiac surgery. However, previous pediatric studies on this topic did not sufficiently adjust for potential confounders and variations in surgeons' techniques.

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Gastrointestinal bleeding in recipients of left ventricular assist devices-a systematic review

The twenty-first century has revolutionized the management of congestive heart failure with the widespread use of left ventricular assist devices and other treatment modalities that improve morbidity and mortality after the failure of medical management.

Fatigue, depression, and product tolerability during long-term treatment with intravenous immunoglobulin (Gamunex® 10%) in patients with chronic inflammatory demyelinating polyneuropathy

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is characterized by progressive weakness and sensory loss, often affecting patient's ability to walk and perform activities of daily living independently. Furthermore, patients often report fatigue and depression which can affect their quality of life.

The unknown functions of a known protein: the case of coagulation factor XI

Over the last years, it became clear that there is considerable cross-talk between various organs, and that this cross-talk plays an instrumental role in disease pathologies. It has for example already been well established that heart failure can unfavorably affect liver function, but also vice versa as non-alcoholic fatty liver disease can increase the risk for heart failure.

No immunological changes after factor VIII product switch: An in-depth analysis in haemophilia A patients

A challenging complication in the treatment of haemophilia A is the formation of neutralizing anti-FVIII antibodies (inhibitors). There is ongoing debate on the effect of FVIII product and inhibitor risk, rendering patients and physicians reluctant to switch FVIII-products.

Hematological treatment and prophylaxis in patients with and without inhibitors

This document focuses on the hematological treatment and prophylaxis that should be indicated in three groups of patients with hemophilia: Patients with inhibitors; Patients without inhibitors; and Patients receiving nonfactor replacement therapy.

Bleeding events in people with congenital haemophilia A without factor VIII inhibitors receiving prophylactic factor VIII treatment: A systematic literature review

Evidence on bleeding rates in people with congenital haemophilia A (PwcHA) without inhibitors on factor VIII (FVIII) replacement products is inconsistent. AIM: This systematic literature review assessed bleeding outcomes in PwcHA using FVIII-containing products as prophylactic treatment.

Recombinant FVIII: the milestone of modern hemophilia treatment

On January 19, 1989, the Medical Intelligence section of the New England Journal of Medicine reported the first use of recombinant factor VIII (FVIII) in two patients with severe hemophilia A (HA). This article represents a landmark in its field because it marks two distinct periods of hemophilia care.

Towards achieving a haemophilia-free mind

Never in history has haemophilia research generated so many therapeutic innovations. Beyond the prevention of bleeding complications, these new treatment options should fundamentally change the lives of those who face this disease.

Emicizumab for acquired haemophilia A: A case series

Emicizumab is approved to prevent bleeding in patients with congenital haemophilia A with or without inhibitors. However, no randomized trials addressed the efficacy of emicizumab in acquired haemophilia A (AHA).

2023

MEI

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Perioperative Outcomes of Patients with Bleeding Disorders Undergoing Major Surgery at an Academic Hemophilia Treatment Center

Persons with bleeding disorders (PwBD) are at high risk for bleeding with invasive procedures. However, the risk of bleeding in PwBD undergoing major surgery and outcomes of patients managed perioperatively at a hemophilia treatment center (HTC) are not well described.

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Coagulation Management and Transfusion in Massive Postpartum Hemorrhage

Excessive bleeding during and following childbirth remains one of the leading causes of maternal mortality.

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Physiological and Clinical Effects of Different Infusion Rates of Intravenous Fluids for Volume Expansion: A Scoping Review

To assess the physiological and clinical effects of different rates of intravenous fluids for volume expansion of critically ill and perioperative patients.

Immune-Mediated Neuropathies: Pathophysiology and Management

Dysfunction of the immune system can result in damage of the peripheral nervous system. The immunological mechanisms, which include macrophage infiltration, inflammation and proliferation of Schwann cells, result in variable degrees of demyelination and axonal degeneration.

Antibody Diversity in IVIG: Therapeutic Opportunities for Novel Immunotherapeutic Drugs

Significant progress has been made in the elucidation of human antibody repertoires. Furthermore, non-canonical functions of antibodies have been identified that reach beyond classical functions linked to protection from pathogens.

Efficacy and Safety Of Damoctocog Alfa Pegol Prophylaxis in Patients ⩾40 Years with Severe Haemophilia A and Comorbidities: Post Hoc Analysis from the PROTECT VIII Study

Advances in treatment have enabled patients with haemophilia A to live longer and therefore may be subjected to comorbidities associated with ageing, in addition to disease-associated morbidities. There have been few reports to date on efficacy and safety of treatment specifically in patients with severe haemophilia A and comorbidities.

A Thrombophilic Allele of Clotting Factor VII/Viia Promoting Recurrent Pulmonary Emboli, Clinical Details, and A Structural Model of the Altered Protein: A Case Report

The clotting or hemostasis system is a meticulously regulated set of enzymatic reactions that occur in the blood and culminate in formation of a fibrin clot. The precisely calibrated signaling system that prevents or initiates clotting originates with the activated Factor Seven (FVIIa) complexed with tissue factor (TF) formed in the endothelium. Here we describe a rare inherited mutation in the FVII gene which is associated with pathological clotting.

Eftrenonacog Alfa: A Review in Haemophilia B

Eftrenonacog alfa (Alprolix((R))) is an extended half-life recombinant factor IX (rFIX)-Fc fusion protein (hereafter referred to as rFIXFc). Administered as an intravenous bolus, it is approved for prophylactic use and the treatment of bleeding in patients with haemophilia B in various countries worldwide, including those of the EU, as well as the USA.

Plasma Kallikrein as a Forgotten Clotting Factor

For decades, it was considered that plasma kallikrein's (PKa) sole function within the coagulation cascade is the activation of factor (F)XII. Until recently, the two key known activators of FIX within the coagulation cascade were activated FXI(a) and the tissue factor-FVII(a) complex. Simultaneously, and using independent experimental approaches, three groups identified a new branch of the coagulation cascade, whereby PKa can directly activate FIX.

A Real-World Evidence Analysis of the Impact of Switching from Factor VIII to Emicizumab Prophylaxis in Patients with Hemophilia A Without Inhibitors

This study retrospectively compared annualized billed bleed rates (ABR(b)) in people with hemophilia A (PwHA) without inhibitors who switched from factor VIII (FVIII) prophylaxis to emicizumab.

Real-World Analysis of Patients with Haemophilia A And Haemophilia A Carriers in The United States: Demographics, Clinical Characteristics, and Costs

Females with haemophilia A (HA [FHAs]) and HA carriers (HACs) have an increased risk of bleeding and complications compared to the general population.

Considerations for Shared Decision Management in Previously Untreated Patients with Hemophilia A or B

Recent advances in therapeutics are now providing a wide range of options for adults and children living with hemophilia. Although therapeutic choices are also increasing for the youngest individuals with severe disease, challenges remain about early management decisions, as supporting data are currently limited.

2023

APRIL

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POST-MARKETING OBSERVATIONAL STUDY OF THE SAFETY AND EFFICACY OF FIBRINOGEN CONCENTRATE IN CONGENITAL FIBRINOGEN DEFICIENCY IN PATIENTS OF ALL AGES

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Comprehensive analysis of coagulation factor delivery strategies in a cohort of trauma patients

The 5th edition of The European recommendations for the management of major bleeding and coagulopathy following trauma leaves room for various coagulation factor administration strategies. The present study examines these strategies reporting prevalence and timing of administration, quantity dispensed, and transfusion ratios in French trauma centers and their compliance with recommendations alongside associated mortality data.

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Perioperative Management of a Patient with Hemophilia C and Allergy to Fresh Frozen Plasma

Hemophilia C is a rare bleeding disorder characterized by a deficiency in clotting factor XI (fXI) and has no standard of care for preoperative optimization before cardiac surgery.

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Potential for prolongation of fibrinogen concentrates post-reconstitution

Reconstituted fibrinogen concentrate is considered stable for 8-24 h based on product monographs. Given the long half-life of fibrinogen in vivo (3-4 days), we hypothesized that reconstituted sterile fibrinogen protein would remain stable longer than 8-24 h.

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Prediction of hypofibrinogenaemia based on the starting fibrinogen and extent of haemodilution during cardiac surgery

It is now recognised that correction of hypofibrinogenaemia is a priority in the management of coagulopathic bleeding, once drug-related causes have been reversed as far as possible.

Increased Access to Immunoglobulin Replacement Therapy for Patients with Primary Immunodeficiency in Poland Based on Clinical Usage Data of Immunoglobulin G over a 5-Year Period

Owing to the rising popularity and demand for immunoglobulins (IgG), obtaining supplies and rationalizing IgG use have become challenging. Herein, IgG consumption in Poland was analyzed through total IgG use and number of patients reported to the National Health Fund between 1 January 2016 and 31 December 2020.

Comparison of IVIg and TPE efficacy in the treatment of neurological disorders: a systematic literature review

Intravenous immunoglobulin (IVIg) and therapeutic plasma exchange (TPE) are among the main immunotherapies for neurological disorders. Their benefit is greatest in immune-mediated conditions, but their distinct efficacy cannot be simply explained.

Use of immunoglobulin replacement therapy in patients with secondary antibody deficiency in daily practice: a European expert Q&A-based review

Secondary antibody deficiencies (SAD) are often a side effect of specific therapies that target B cells directly or affect the antibody response indirectly. Treatment of immunodeficiency by immunoglobulin replacement therapy (IgRT) is well established in primary antibody deficiencies, although the evidence for its use in SAD is less well established.

Secondary immunodeficiencies and infectious considerations of biologic immunomodulatory therapies

Biologic immunomodulatory medications have rapidly expanded in the previous decades, providing new treatment options for individuals with a spectrum of oncologic, allergic, rheumatologic, and neurologic conditions.

Intravenous Immunoglobulin: Mechanism of Action in Autoimmune and Inflammatory Conditions

IVIG is the mainstay of therapy for humoral immune deficiencies and numerous inflammatory disorders.

Real pandemic world results of pharmacokinetic-tailored personalized prophylaxis of bleeds in Polish children and adolescents with severe hemophilia A

In 2020, the new nationwide protocol of prophylaxis in Polish plasma-derived FVIII (pdFVIII) previously treated patients (PTPs) with severe hemophilia A (sHA) was introduced, resulting in the necessity of switching from pdFVIII to recombinant FVIII (octocog-alpha; rFVIII).

Current Understanding of Inherited Modifiers of FVIII Pharmacokinetic Variation

The inherited bleeding disorder hemophilia A involves the quantitative deficiency of the coagulation cofactor factor VIII (FVIII).

Health Related Quality of Life and Psychopathological Symptoms in People with Hemophilia, Bloodborne Co-Infections and Comorbidities: An Italian Multicenter Observational Study

The health-related quality of life (HRQoL) of people with hemophilia (PWH) is an important issue, especially considering people suffering from chronic diseases beyond hemophilia. The principal aim of this study was to investigate the presence and relevance of psychological symptoms, both internalizing and externalizing, lifestyle, and HRQoL in a group of Italian PWH with chronic bloodborne co-infections and comorbidities.

Haemophilia A: A Review of Clinical Manifestations, Treatment, Mutations, and the Development of Inhibitors

The purpose of this narrative review was to provide an overview that allows readers to improve their understanding of hemophilia A, which is considered a genetic disease with a high impact on the quality of life of people who suffer from it is considered one of the diseases with the highest cost for health systems (In Colombia it is part of the five diseases with the greatest economic impact).

Suspected adverse reactions reported for blood, blood components, and blood products in VigiBase

Since being designated as medicines by World Health Organization (WHO), blood components are subject to pharmacovigilance reporting. Using VigiBase, the WHO global database of individual case safety reports (ICSRs), we characterized reports of adverse reactions for all blood products.

Alpha-1 antitrypsin deficiency: current therapy and emerging targets

Alpha1 antitrypsin deficiency (AATD), a common hereditary disorder affecting mainly lungs, liver and skin has been the focus of some of the most exciting therapeutic approaches in medicine in the past 5 years.

Prenatal screening service for fetal RHD genotyping to guide prophylaxis: the two-year experience of the Friuli Venezia Giulia region in Italy

Fetal RHD genotyping of cell-free fetal DNA (cff-DNA) from RhD-negative pregnant women can be used to guide anti-D prophylaxis: the knowledge of fetal RhD type can direct and restrict the use of prenatal anti-D immunoglobulin exclusively to RhD-negative women carrying a RhD-positive fetus. Since November 2019 in the region of Friuli Venezia Giulia (Italy) a prenatal screening service has been offered to RhD-negative women at 22-24 weeks of gestation.

Factor VII Activating Protease (FSAP) and Its Importance in Hemostasis-Part I: FSAP Structure, Synthesis and Activity Regulation: A Narrative Review

Factor VII activating protease (FSAP) was first isolated from human plasma less than 30 years ago. Since then, many research groups have described the biological properties of this protease and its role in hemostasis and other processes in humans and other animals.

Efanesoctocog Alfa: First Approval

Efanesoctocog alfa (ALTUVIIIO(TM); [antihemophilic factor (recombinant), Fc-VWF-XTEN fusion protein-ehtl]), a von Willebrand factor (VWF) independent, recombinant DNA-derived Factor VIII (FVIII) concentrate, has been developed by Bioverativ Therapeutics, Inc (a Sanofi company) and Swedish Orphan Biovitrum AB (Sobi).

Current factor IX replacement options for hemophilia B and the challenges ahead

Therapy for hemophilia B is aimed at replacing the congenital deficiency of coagulation factor IX (FIX). For replacement therapy, several FIX concentrates derived from donated human plasma or engineered by recombinant DNA technology are currently commercially available. The use of these products is well established and permit patients a relatively normal life.

Impact of switching prophylaxis treatment from factor VIII to emicizumab in hemophilia A patients without inhibitors

Factor VIII (FVIII) replacement and emicizumab are effective at preventing bleeds in patients with hemophilia A (HA). Though benefits of emicizumab among inhibitor patients with HA (PwHA) are well established, more real-world evidence among non-inhibitor patients is needed.

Budget impact of prophylactic treatment of rVIII-SingleChain in moderate and severe hemophilia A in Italy

rVIII-SingleChain, a recombinant factor VIII (rFVIII), has demonstrated safety and efficacy in patients with hemophilia A in clinical trials and real-world evidence. This analysis aimed to estimate the potential budget impact of increasing the usage of rVIII-SingleChain for the prophylactic treatment of hemophilia A over 3 years in Italy.

Clinical Predictors and Prediction Models for rFVIII-Fc Half Life in Real-World People with Severe Hemophilia A

The half-life of recombinant factor VIII-Fc (rFVIII-Fc) for people with hemophilia A (PwHA) varies greatly. Understanding the factors influencing the variation and assessment of rFVIII-Fc half-life is important for personalized treatment.

Safe and Successful Surgical Outcome in Persons with Hemophilia A with and without Inhibitors Treated with Emicizumab: A Large, Single Center, Real-World Experience

Emicizumab is a humanized recombinant bispecific antibody, bridging together activated factor IX (FIXa) and factor X (FX), thus mimicking the activity of FVIII in vivo. Emicizumab is designed for long-term prophylaxis in patients with severe hemophilia A with and without inhibitors.

Immune tolerance against infused FVIII in hemophilia A is mediated by PD-L1(+)

A major complication of hemophilia A therapy is the development of alloantibodies (inhibitors) that neutralize intravenously administered coagulation factor VIII (FVIII). Immune tolerance induction therapy (ITI) by repetitive FVIII injection can eradicate inhibitors, and thereby reduce morbidity and treatment costs.

EU gets first hemophilia B gene therapy

The European regulator has given gene therapy Hemgenix from uniQure/CSL Behring a conditional approval, making it the first in the region for treating hemophilia B.

2023

MAART

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Alternative blood products in trauma

Hemorrhage and trauma-induced coagulopathy cause significant morbidity and mortality in trauma patients. Although blood products are the cornerstone of resuscitation, these resources are scarce, necessitating alternatives. This review examines the use of alternative blood products in trauma as well as the literature supporting their use.

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Blood Product Replacement for Postpartum Hemorrhage

Consideration for blood products replacement in postpartum hemorrhage should be given when blood loss exceeds 1.5 L or when an estimated 25% of blood has been lost.

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Comparison of Prothrombin Complex Concentrate with Activated Factor VII Use for Bleeding Following Cardiopulmonary Bypass in Children

This study aims to compare the efficacy and safety of activated recombinant factor VII (rFVIIa) and prothrombin complex concentrate (PCC) in the treatment of bleeding complications following surgery requiring cardiopulmonary bypass (CPB) in children.

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Transfusion Management in Trauma: What is Current Best Practice?

In the past few years, transfusion strategies in trauma have changed dramatically. We aim to define current practices, explore the evidence leading to these shifts, and identify areas of contemporary research within this field.

Intravenous and subcutaneous immunoglobulins-associated eczematous reactions occur with a broad range of immunoglobulin types: A French national multicenter study

Human immunoglobulins are used for treating diverse inflammatory and autoimmune disorders. Eczema is an adverse event reported but poorly described.

Management of hypogammaglobulinemia

Hypogammaglobulinemia (hypoγ) is defined as a serum IgG level < 7 g/L. It is most often detected on serum protein electrophoresis. Given the existence of transient hypoγ, its persistence should be checked at distance, preferably by requesting a blood test for IgG, IgA and IgM, which will be needed to characterize a possible primary immune deficiency (PID).

Immune globulin usage trends in commercially insured and Medicare populations, 2009–2019

Longitudinal patterns of immune globulins (IG) use have not been described in large populations. Understanding IG usage is important given potential supply limitations impacting individuals for whom IG is the sole life-saving/health-preserving therapy. The study describes US IG utilization patterns from 2009 to 2019.

Intravenous immunoglobulin in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP): mechanisms of action and clinical and genetic considerations

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an autoimmune peripheral nerve disorder that is characterized by subacute onset, progressive or relapsing weakness, and sensory deficits. Proven treatments include intravenous immunoglobulin (IVIg), corticosteroids, and plasma exchange. This review focuses on the mechanisms of action, pharmacodynamics, genetic variations, and disease characteristics that can affect the efficacy of IVIg.

2023

FEBRUARI

Acquired Hemophilia A: An Update on the Etiopathogenesis, Diagnosis, and Treatment

Acquired haemophilia A (AHA) is a rare bleeding disorder caused by inhibitory autoantibodies against coagulation factor VIII (FVIII). AHA is a disease that most commonly affects the elderly but has also been observed in children and in the postpartum period.

Management of rare inherited bleeding disorders: Proposals of the French Reference Centre on Haemophilia and Rare Coagulation Disorders

The rare coagulation disorders may present significant difficulties in diagnosis and management. In addition, considerable inter-individual variation in bleeding phenotype is observed amongst affected individuals, making the bleeding risk difficult to assess in affected individuals.

Prevalence of selected bleeding and thrombotic events in persons with hemophilia versus the general population: A scoping review

Life expectancy for persons with hemophilia has increased over recent decades due to advances in treatment practice and patient care. Those with hemophilia are now more likely to be affected by conditions associated with aging, such as myocardial infarction, hemorrhagic/ischemic stroke, deep vein thrombosis, pulmonary embolism, and intracranial hemorrhage.

Genetic determinants of enhanced von Willebrand factor clearance from plasma

Enhanced von Willebrand factor (VWF) clearance from plasma is associated with von Willebrand disease (VWD). However, the genetic background of this disease mechanism is not well defined.

Factor XI inhibitors: what should clinicians know

Factor XI (FXI) inhibitors were developed to address unmet needs and limitations of current anticoagulants and are currently being studied in several indications. In this paper, we review the rationale for the development of these agents and summarize what clinicians should know about drugs that target FXI.

von Willebrand factor neutralizing and non-neutralizing alloantibodies in 213 subjects with type 3 von Willebrand disease enrolled in 3WINTERS-IPS

Type 3 von Willebrand disease (VWD) is the most severe form of this disease owing to the almost complete deficiency of von Willebrand factor (VWF). Replacement therapy with plasma-derived products containing VWF or recombinant VWF rarely cause the development of alloantibodies against VWF that may be accompanied by anaphylactic reactions.

Von Willebrand Disease, Hemophilia, and Other Inherited Bleeding Disorders in Pregnancy

Inherited bleeding disorders, which comprise von Willebrand disease (VWD), hemophilia, other congenital clotting factor deficiencies, inherited platelet disorders, defects of fibrinolysis, and connective tissue disorders, have both maternal and fetal implications.

Determinants of successful immune tolerance induction in hemophilia A: systematic review and meta-analysis

Immune tolerance induction (ITI) aims to eradicate anti-factor VIII (FVIII) antibodies (inhibitors) in persons with hemophilia A. However, this burdensome treatment fails in 10% to 40%. To estimate the chance of ITI success in clinical decision making, it is important to identify the predictors of ITI success.

Emicizumab in people with moderate or mild haemophilia A (HAVEN 6): a multicentre, open-label, single-arm, phase 3 study

Clinical trial data are scarce for the use of prophylaxis in people with non-severe haemophilia A. The HAVEN 6 study aims to assess safety and efficacy of emicizumab prophylaxis in people with non-severe haemophilia A without factor VIII (FVIII) inhibitors.

Long-term impact of primary prophylaxis on joint status in patients with severe hemophilia A

Primary prophylaxis with factor VIII concentrates is the therapeutic gold standard for severe hemophilia A. Although this approach will change substantially with the use of nonsubstitutive therapies, the long-term effects of primary prophylaxis remain unclear.

Hemophilia treatment innovation: 50 years of progress and more to come

With the goal of emphasizing the striking advances that materialized in hemophilia care particularly in the last 10 years, the progress of knowledge that started from the 1970s will first be sketched as background.

Acquired Haemophilia A in four north European countries: survey of 181 patients

Acquired haemophilia A (AHA) is a rare bleeding disorder caused by acquired antibodies against coagulation factor VIII. In the Nordic countries, treatment and outcomes have not been studied in recent times.

50 Years of Pediatric Hemostasis: Knowledge, Diagnosis, and Treatment

Studies from the past 50 years have contributed to the expanding knowledge regarding developmental hemostasis. This is a dynamic process that begins in the fetal phase and is characterized by physiological variations in platelet counts and function, and concentrations of most coagulation factors and the native coagulation inhibitors in early life, as compared with adulthood.

Surgical outcomes in people with hemophilia A taking emicizumab prophylaxis: experience from the HAVEN 1-4 studies

Many people with hemophilia A (PwHA) undergo surgery in their lifetime, often because of complications of their disease. Emicizumab is the first bispecific monoclonal antibody prophylactic therapy for PwHA, and its efficacy and safety have been previously demonstrated; however, there is a need to build an evidence base on the management of PwHA on emicizumab undergoing surgery.

An evaluation of von Willebrand factor (recombinant) therapy for adult patients living with severe type 3 von Willebrand disease

Von Willebrand Factor (VWF) containing concentrates have been used for the treatment of von Willebrand Disease (VWD) for many years. Recently, however, a novel recombinant VWF (rVWF or vonicog alpha, VONVENDI [US], VEYVONDI [Europe]) has arrived to the market for the treatment of VWD.

A French Real-World Evidence Study Evaluating the Efficacy, Safety, and Pharmacokinetic Parameters of rVIII-SingleChain in Patients with Hemophilia A Receiving Prophylaxis

rVIII-SingleChain is a recombinant factor VIII (FVIII) with increased binding affinity to von Willebrand factor compared with other FVIII products. rVIII-SingleChain is indicated for the treatment and prevention of bleeding episodes in patients with hemophilia A.

Trends in prescribing practices for management of haemophilia: 1999-2021

People with haemophilia rely on specialists for their care, yet the specific dosing regimens of treatments prescribed by these specialists have not been widely studied. AIM: The objective of this study is to describe trends in clinician prescribing practices for the management of haemophilia in the United States (US).

Mild and Moderate Hemophilia A: Neglected Conditions, Still with Unmet Needs

Hemophilia A (HA) is an inherited X-linked bleeding disorder, caused by the deficiency of coagulation factor VIII (FVIII), with variable clinical phenotypes […].

Evaluating the financial impact of utilizing recombinant porcine factor VIII or recombinant FVIIa for patients with acquired hemophilia A

To evaluate the financial impact of utilizing rpFVIII or rFVIIa during a hospital admission for the diagnosis of acquired hemophilia A (AHA) by reviewing the margin between the cost to the hospital for providing care and the amount the hospital is reimbursed by the Centers for Medicare & Medicaid Services (CMS) in the US.

Comparison of Prothrombin Complex Concentrate with Activated Factor VII Use for Bleeding Following Cardiopulmonary Bypass in Children

This study aims to compare the efficacy and safety of activated recombinant factor VII (rFVIIa) and prothrombin complex concentrate (PCC) in the treatment of bleeding complications following surgery requiring cardiopulmonary bypass (CPB) in children.

Blood coagulation and beyond: Position paper from the Fourth Maastricht Consensus Conference on Thrombosis

The 4th Maastricht Consensus Conference on Thrombosis (MCCT), included 5 themes.

Efficacy and safety of von Willebrand factor concentrate almost devoid of factor VIII (Wilfactin®) in paediatric patients under 6 years of age with severe von Willebrand disease

Plasma-derived von Willebrand factor (VWF) (Wilfactin®, LFB, France) was developed for prophylaxis and treatment of haemorrhages in both adults and adolescents with von Willebrand disease (VWD). Replacement therapy in paediatric patients is a key element of the clinical trial programme.

Eptacog Beta (rFVIIa) Has a Low Incidence of Spontaneous Rebleeding through 24 and 48 Hours in Adult and Adolescent Patients with Hemophilia A or B with Inhibitors

Abstract: not available

2023

JANUARI

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Intraoperative transfusion management, antifibrinolytic therapy, coagulation monitoring and the impact on short-term outcomes after liver transplantation-A systematic review of the literature and expert panel recommendations

Liver transplantation (LT) is frequently complicated by coagulopathy associated with end-stage liver disease (ESLD), that is, often multifactorial. OBJECTIVES: The objective of this systematic review was to identify evidence based intraoperative transfusion and coagulation management strategies that improve immediate and short-term outcomes after LT.

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Association of Whole Blood With Survival Among Patients Presenting With Severe Hemorrhage in US and Canadian Adult Civilian Trauma Centers

Whole-blood (WB) resuscitation has gained renewed interest among civilian trauma centers. However, there remains insufficient evidence that WB as an adjunct to component therapy–based massive transfusion protocol (WB-MTP) is associated with a survival advantage over MTP alone in adult civilian trauma patients presenting with severe hemorrhage.

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Comparison of factor products for treatment of bleeding related to cardiac surgery

Recombinant factor VIIa (rFVIIa) and 4-factor prothrombin concentrate complex (PCC) are often used for uncontrolled bleeding in cardiac surgery, however, there are limited direct comparisons of these agents. The objective of this study is to evaluate the efficacy and safety of rFVIIa and PCC in cardiac surgery related bleeding.

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Cost-effectiveness of Fibrinogen Concentrate vs Cryoprecipitate for Treating Acquired Hypofibrinogenemia in Bleeding Adult Cardiac Surgical Patients

Excessive bleeding requiring fibrinogen replacement is a serious complication of cardiac surgery. However, the relative cost-effectiveness of the 2 available therapies-fibrinogen concentrate and cryoprecipitate-is unknown.

Predicting Outcome in Guillain-Barré Syndrome: International Validation of the Modified Erasmus GBS Outcome Score

The clinical course and outcome of the Guillain-Barré syndrome (GBS) are diverse and vary among regions. The modified Erasmus GBS Outcome Score (mEGOS), developed with data from Dutch patients, is a clinical model that predicts the risk of walking inability in patients with GBS. The study objective was to validate the mEGOS in the International GBS Outcome Study (IGOS) cohort and to improve its performance and region specificity.

Primary prophylaxis in children with severe haemophilia A and B-Implementation over the last 20 years as illustrated in real-world data in the PedNet cohorts

The prophylactic regimen in children with severe haemophilia is suggested in various publications and guidelines. Few data exist on its implementation in clinical practice.

Vaccine-induced immune thrombotic thrombocytopenia

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is primarily a complication of adenoviral vector-based covid-19 vaccination.

The diagnosis, natural history, and management of von Willebrand disease in women in the age of guidelines

Women and girls with bleeding disorders face multiple bleeding challenges throughout their life. The most significant morbidity and mortality are due to heavy menstrual bleeding and postpartum hemorrhage in their reproductive years.

The effect of recombinant versus plasma-derived von Willebrand factor on prolonged PFA closure times in ECMO patients with acquired von Willebrand syndrome - an observational study

Extracorporeal membrane oxygenation (ECMO) is applied in patients with respiratory or cardiopulmonary failure, but bleeding is a frequent complication contributing to the high mortality rates in this patient collective.

Cost analysis of extended half-life recombinant factor IX products in the treatment of haemophilia B in Italy: an update

Haemophilia B (HB) is a rare disease which may lead to chronic disabling arthropathy, resulting in a significant clinical, social and economic impact. In recent years, new extended half-life (EHL) factor IX concentrates produced by recombinant technology (rFIX) have been developed.

2022

DECEMBER

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The role of fibrinogen in postpartum hemorrhage

Postpartum hemorrhage (PPH) is the leading cause of maternal death worldwide (WHO), with almost 60000 deaths annually.

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Major haemorrhage: past, present and future

Major haemorrhage is a leading cause of morbidity and mortality worldwide. Successful treatment requires early recognition, planned responses, readily available resources (such as blood products) and rapid access to surgery or interventional radiology.

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Effect of fibrinogen replacement therapy on bleeding outcomes and 1-year mortality in patients undergoing thoracic aortic surgery: a retrospective cohort study

This study aimed to examine the effect of fibrinogen replacement therapy with cryoprecipitate or fibrinogen concentrate on bleeding outcomes and 1-year mortality in patients undergoing thoracic aortic surgery.

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Pharmacokinetics, efficacy and safety of a novel fibrinogen concentrate in pediatric patients with congenital afibrinogenemia

Congenital afibrinogenemia treatment with plasma-derived fibrinogen concentrates in pediatric patients is limited. This study investigated the pharmacokinetics, surrogate efficacy, and safety of a plasma-derived fibrinogen concentrate (FIB Grifols) in pediatric patients with congenital afibrinogenemia.

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Protocol for postpartum haemorrhage including massive transfusion

Postpartum haemorrhage (PPH) is one of the most common causes of maternal mortality worldwide. Management of PPH depends on the severity of bleeding.

Efficacy and safety of BT595 (10% human intravenous immunoglobulin) in adult patients with chronic immune thrombocytopenia

This trial investigated the efficacy and safety of the new 10% human intravenous immunoglobulin (IVIg) BT595 (Yimmugo®).

Intravenous immunoglobulin in the management and outcome of Stiff-Person syndrome: A systematic review

BACKGROUND: Stiff Person Syndrome (SPS), a rare immune-mediated neuromuscular disorder, is characterized by rigidity, stiffness, and intermittent spasms of axial and extremity muscles. Various immunotherapies including intravenous immunoglobulin (IVIG) have been used for this autoimmune condition. Here we aim to review the role of IVIG in the treatment of SPS along with its outcome.

A multicenter, real-world experience with recombinant FXIII for the treatment of patients with FXIII deficiency: from pharmacokinetics to clinical practice. The Italian FXIII Study

Congenital factor XIII (FXIII) deficiency is a rare coagulation disorder characterized by muscular or mucocutaneous bleeding with life-threatening intracranial hemorrhages (ICHs), especially in cases with severe disease. The best treatment is the use of prophylactic plasma-derived or recombinant FXIII (rFXIII). Few data on the use of rFXIII in the real-world scenario are available. The main goal of this study was to assess the efficacy and safety of catridecacog (NovoThirteen(®)) in a population of patients with FXIII deficiency.

What have we learned about the patient's experience of von Willebrand disease? A focus on women

Von Willebrand disease (VWD), the most common inherited bleeding disorder (IBD), disproportionately affects females, given the hemostatic challenges they may encounter throughout their lifetimes.

Perioperative continuous infusions of factor VIII versus factor IX for patients with hemophilia A or B undergoing major surgery

Continuous factor VIII (FVIII) or factor IX (FIX) infusions are commonly used for patients with hemophilia A (HA) or B (HB) undergoing surgery to secure perioperative hemostasis. To describe differences between the initial recovery and subsequent FIX and FVIII levels and describe clinical outcomes among HB and HA patients receiving perioperative continuous infusion (CI) of recombinant FVIII and FIX concentrates.

Plasma-derived factor VIIa and factor X mixture agent (MC710) prophylaxis in haemophilia B patients with inhibitors

Haemophilia B patients with factor IX inhibitors have particularly unmet needs for conventional therapy. AIM: Phase II/III clinical trial, multicentre, open-label, prospective, self-controlled study was conducted to assess MC710 prophylaxis in haemophilia B patients with inhibitors.

Area under the curve: Comparing the value of factor VIII replacement therapies in haemophilia A

In factor VIII (FVIII) prophylaxis for haemophilia A, cost comparisons have used price per international unit (IU) based on the once reasonable assumption of equivalent outcome per IU. Now, with several extended half-life (EHL) products available, new outcome-oriented ways to compare products are needed.

Acquired Haemophilia A: A Review of What We Know

Autoantibodies against plasma coagulation factors could be developed by some individuals inducing severe and sometimes fatal bleedings. This clinical entity is called acquired haemophilia.

Acquired Factor XIII Deficiency in Patients with Multiple Trauma

Fibrin stabilizing factor (FXIII) plays a crucial role in blood clotting, tissue repair, and immune defense. FXIII deficiency after trauma can lead to prolonged wound healing due to persistent infections or coagulation disorders.

Stable and durable factor IX levels in hemophilia B patients over 3 years post etranacogene dezaparvovec gene therapy

Etranacogene dezaparvovec (AMT-061) is a recombinant adeno-associated virus serotype 5 (AAV5) vector containing a codon-optimized Padua variant human factor IX (FIX) transgene with a liver-specific promoter. Here we report 3-year outcomes from a Phase 2b, open-label, single-dose, single-arm, multi-center trial (NCT03489291) conducted in adults with severe or moderately severe hemophilia B (FIX ≤2%).

von Willebrand factor links primary hemostasis to innate immunity

The plasma multimeric glycoprotein von Willebrand factor (VWF) plays a critical role in primary hemostasis by tethering platelets to exposed collagen at sites of vascular injury. Recent studies have identified additional biological roles for VWF, and in particular suggest that VWF may play an important role in regulating inflammatory responses.

Economic Evaluation of Immune Tolerance Induction in Children with Severe Hemophilia A and High-Responding Inhibitors: A Cost-Effectiveness Analysis of Prophylaxis with Emicizumab

This study aimed to measure the cost-effectiveness of prophylaxis with emicizumab in PsHAhri on ITI in Brazil.

Recombinant Alpha-1 Antitrypsin as Dry Powder for Pulmonary Administration: A Formulative Proof of Concept

Alpha-1 antitrypsin (AAT) deficiency is a genetic disorder associated with pulmonary emphysema and bronchiectasis.

2022

NOVEMBER

Global epidemiology of factor XI deficiency: A targeted review of the literature and foundation reports

Hereditary factor XI (FXI) deficiency is a rare coagulation disorder that may result in excessive bleeding requiring intervention to restore haemostasis. The aim of this review was to report the current knowledge of the worldwide incidence and prevalence of FXI deficiency.

Analysis of von Willebrand Disease in the "Heart of Europe"

von Willebrand disease (VWD) is a genetic bleeding disorder caused by defects of von Willebrand factor (VWF), quantitative (type 1 and 3) or qualitative (type 2). The laboratory phenotyping is heterogenic making diagnosis difficult.

Comprehensive analysis and prediction of long-term durability of factor IX activity following etranacogene dezaparvovec gene therapy in the treatment of hemophilia B

Congenital hemophilia B is a rare bleeding disorder caused by defects in the gene encoding factor IX (FIX) leading to coagulation deficiency. Recurrent bleeds may cause chronic pain, disability, and reduced quality of life.

Emicizumab dose up-titration in case of suboptimal bleeding control in people with haemophilia A

Emicizumab promotes effective haemostasis in people with haemophilia A (PwHA). It is indicated for routine prophylaxis of bleeding episodes in PwHA with or without factor (F)VIII inhibitors.

Applicability of the European Society of Cardiology Guidelines on the management of acute coronary syndromes to older people with haemophilia A - A modified Delphi consensus by the ADVANCE Working Group

As people with haemophilia (PWH) receive better treatment and live longer they are more likely to encounter cardiovascular disease (CVD) and other comorbidities. ESC guidelines for the acute management of patients presenting with acute coronary syndrome (ACS) are based on the non-haemophilia population.

Safety of FEIBA and emicizumab (SAFE): Dose escalation study evaluating the safety of in vivo administration of activated prothrombin complex concentrate in haemophilia A patients on emicizumab

Emicizumab is a humanized bispecific monoclonal antibody licensed for patients with severe haemophilia A. Breakthrough bleeding still occurs in patients on emicizumab and can be managed with recombinant factor VIIa (rFVIIa) or activated prothrombin complex concentrate (aPCC). Thrombotic events were reported when patients on emicizumab received concomitant aPCC at relatively high doses. We studied the effect of infusing various doses of aPCC to patients on emicizumab.

Updates on Novel Non-Replacement Drugs for Hemophilia

Over the last decade, the world of hemophilia has experienced an unprecedented therapeutic advance, thanks to the progress in bioengineering technologies, leading to the introduction of drugs with novel mechanisms of action based on restoring thrombin generation or coagulation factor VIII mimicking.

A Diagnostic of Acquired Hemophilia Following PD1/PDL1 Inhibitors in Advanced Melanoma: The Experience of Two Patients and a Literature Review

Acquired hemophilia A (AHA) is a rare bleeding disorder caused by the development of specific autoantibodies against factor VIII (FVIII). Immunotherapy is a recent therapeutic option that targets the patient’s self-tolerance against tumor cells.

Von Willebrand Disease-Specific Aspects in Women

Von Willebrand disease (VWD) is the most common inherited bleeding disorder, which results from a deficiency or dysfunction of von Willebrand factor (VWF). The major symptoms of patients affected by VWD include mucocutaneous and gastrointestinal bleeding, easy bruising, and prolonged provoked bleeding due to injury or surgery. Although women and men are equally likely to be affected by VWD, women continue to be disproportionately affected by the bleeding challenges.

Update on platelet procoagulant mechanisms in health and in bleeding disorders

Platelet procoagulant mechanisms are emerging to be complex and important to achieving haemostasis. The mechanisms include the release of procoagulant molecules from platelet storage granules, and strong agonist-induced expression of procoagulant phospholipids on the outer platelet membrane for tenase and prothrombinase assembly.

Long-term efficacy, safety, and tolerability of a subcutaneous immunoglobulin 16.5% (cutaquig (R)) in the treatment of patients with primary immunodeficiencies

A prospective study and its long-term extension examined whether weekly treatment of patients with primary immunodeficiencies (PIDs) with a 16.5% subcutaneous immunoglobulin (SCIg; cutaquig (R)) confers acceptable efficacy, safety, and tolerability over a follow-up of up to 238 weeks (>4 years).

French recommendations for the management of adult & pediatric chronic inflammatory demyelinating polyradiculoneuropathy (CIDP)

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a rare autoimmune disorder of the peripheral nervous system, primarily affecting the myelin sheath. The pathophysiology of CIDP is complex, involving both humoral and cellular immunity.

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Comparison of European recommendations about patient blood management in postpartum haemorrhage

Postpartum haemorrhage (PPH) is the leading cause of maternal mortality and morbidity worldwide. Some documents with practical recommendations for the management of PPH do not include the most updated directives. This review offers a quality comparison of the recommendations stated in Europe since 2015.

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Transfusion management in the trauma patient

Transfusion of blood products is lifesaving in the trauma ICU. Intensivists must be familiar with contemporary literature to develop the optimal transfusion strategy for each patient.

Structure and Function of Recombinant versus Plasma-Derived von Willebrand Factor and Impact on Multimer Pharmacokinetics in von Willebrand Disease

Recombinant von Willebrand factor (rVWF, vonicog alfa) is a purified VWF concentrate produced from Chinese hamster ovary cells. rVWF is not exposed to the VWF-cleaving protease ADAMTS13 and so is not subject to proteolytic degradation of large (L) and ultra-large (UL) VWF multimers by that enzyme.

The detrimental effects of iron to the joint; aggravation by inflammation

With great interest, we read the article ‘Which part of the blood in the knee joint is responsible for its detrimental effects? (An experimental study on the knee joint in rabbits)’ which was recently published in Haemophilia.1 Colak et al. investigated the influence of different blood components on joint damage by injecting them separately into a rabbit knee.

IDEAL study: A real-world assessment of pattern of use and clinical outcomes with recombinant coagulation factor IX albumin fusion protein (rIX-FP) in patients with haemophilia B in Italy

Factor IX replacement therapy is used for treatment and prophylaxis of bleeding in haemophilia B. rIX-FP is an extended half-life albumin-fusion protein, which, in clinical studies, has demonstrated prolonged dosing intervals up to 21 days for routine prophylaxis, providing therapeutic benefit.

Clinical significance of substantially elevated von Willebrand factor antigen levels in patients with advanced chronic liver disease

Von Willebrand factor antigen (VWF) is a non-invasive marker for clinically significant portal hypertension (HVPG >= 10 mmHg) and confers HVPG-independent prognostic information. While quantification of increased VWF-levels is not relevant in the context of von Willebrand disease, highly elevated VWF may be of clinical significance in ACLD.

Cost-effectiveness of recombinant factor VIII Fc versus emicizumab for prophylaxis in adults and adolescents with haemophilia A without inhibitors in the UK

The economic and clinical burden of haemophilia A is high. Primary prophylaxis with factor VIII replacement therapy is the recognized standard of care, but the emergence of non-factor therapies, such as emicizumab, is extending treatment options for people with haemophilia A.

Drug-associated acquired hemophilia A: an analysis based on 185 cases from the WHO pharmacovigilance database

Acquired hemophilia A (AHA) is a rare autoimmune hemorrhagic disease occurring in several underlying conditions. Drug-associated AHA (D-AHA) is poorly addressed nowadays.

Kinetic and Dynamic Effects on Degradation of von Willebrand Factor

The loss of high molecular weight multimers (HMWM) of von Willebrand factor (vWF) in aortic stenosis (AS) and continuous-flow left ventricular assist devices (cf-LVADs) is believed to be associated with high turbulent blood shear.

Molecular basis of rare congenital bleeding disorders

Rare bleeding disorders (RBDs), including factor (F) I, FII, FV, FVII, combined FV and FVIII (CF5F8), FXI, FXIII and vitamin-K dependent coagulation factors (VKCF) deficiencies, are a heterogeneous group of hemorrhagic disorder with a variable bleeding tendency.

Reproductive health and hemostatic issues in women and girls with congenital factor VII deficiency: A systematic review

Congenital factor VII (FVII) deficiency is an inherited bleeding disorder, with heterogenous bleeding symptoms. Women with FVII deficiency face hemostatic challenges during menstruation, ovulation, and childbirth. This systematic review evaluated prevalence and management of bleeding symptoms associated with gynecological and obstetric issues in women with FVII deficiency.

Economic impact of self-administered subcutaneous versus clinic-administered intravenous immunoglobulin G therapy in Alberta, Canada: a population-based cohort study

Self-administered subcutaneous immunoglobulin G (SCIg) reduces nursing time and eliminates the need for treatment at ambulatory care clinics, as compared with clinic-based intravenously administered IgG (IVIg) and are therapeutically equivalent. Estimating the economic impact of self-administered SCIg versus clinic-administered IVIg therapy may guide treatment recommendations.

Subcutaneous immunoglobulin 16.5% for the treatment of pediatric patients with primary antibody immunodeficiency

Human immunoglobulin (IG) is extracted from the plasma of donors as a sterile, purified blood product that is administered intravenously (via a vein [IVIG]) or subcutaneously (under the skin [SCIG]) and is used for a variety of disorders, including the prevention of infections in patients with primary immunodeficiency diseases (PIDDs) such as primary antibody immunodeficiencies.

Cutaquig(®) Is Well Tolerated in Immunodeficient Patients Who Did Not Tolerate Other Subcutaneous Immunoglobulin Products

Subcutaneous immunoglobulin (SCIG) treatment is generally tolerable, but some patients may experience adverse events to one or more SCIG products. We investigated whether 16.5% Cutaquig(®) treatment offered a tolerable and safe alternative treatment for immunodeficient patients.

The Choice between Intravenous and Subcutaneous Immunoglobulins: Aspects for Consideration

Intravenous immunoglobulin and subcutaneous immunoglobulin preparations are used to treat primary and secondary immunodeficiencies, as well as autoimmune and inflammatory conditions.

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Comparison of fibrinogen concentrates to cryoprecipitate in restoring clot integrity and stability against fibrinolytic degradation

Fibrinogen depletion is a critical feature in trauma induced coagulopathy (TIC). Cryoprecipitate or fibrinogen concentrates can be administered to restore levels of this clotting factor.

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Audit of the use of Fibclot (Fibrinogen concentrate) in patients without congenital afibrinogenaemia

Fibclot is licensed for use in patients with congenital hypo or afibrinogenaemia with a bleeding tendency. The recommended initial dose in an emergency situation is 0.05 g per kg of body weight aiming for a level of 1 g/l in non-surgical bleeding.

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Pregnancy and childbirth in women with bleeding disorders: A retrospective cohort study

Reproductive-age women with bleeding disorders (BDs) are underdiagnosed and understudied, despite their increased risk for adverse health outcomes and pregnancy complications.

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Coagulopathy management of multiple injured patients - a comprehensive literature review of the European guideline 2019

The European guideline on the management of trauma-induced major bleeding and coagulopathy summarises the most relevant recommendations for trauma coagulopathy management.

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Management of Antithrombin Deficiency in Pregnancy

Antithrombin (AT) deficiency is a high-risk thrombophilia and a rare condition. The risk of venous thromboembolism (VTE) is increased in AT-deficient women during pregnancy and the postpartum period and is especially high in women with a prior history of VTE.

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Viscoelastic versus conventional coagulation tests to reduce blood product transfusion in patients undergoing liver transplantation: A systematic review and meta-analysis

Recent literature suggests viscoelastic test (VET)-guided transfusion management could be associated with reduced blood product administration in patients undergoing liver transplantation.

2022

OKTOBER

Prophylactic Recombinant Factor VIIa for Preventing Massive Transfusion During Orthotopic Liver Transplantation

Recombinant human activated factor VIIa has been used prophylactically to mitigate requirements for transfusion in liver transplant. We explored its effectiveness and risks among liver transplant recipients at high risk for massive transfusion.

Thrombin generation for monitoring hemostatic therapy in hemophilia A: A narrative review

Patients with severe hemophilia A (HA) have an increased risk of spontaneous and trauma-related bleeding because of a congenital absence of factor VIII (FVIII).

Alpha-1 Antitrypsin Deficiency Liver Disease

Liver disease in homozygous ZZ alpha-1 antitrypsin (AAT) deficiency occurs due to the accumulation of large quantities of AAT mutant Z protein polymers in the liver.

Efficacy and safety in patients with haemophilia A switching to octocog alfa (BAY 81-8973): Final results of the global real-world study, TAURUS

To report the final results of the 2-year TAURUS study, assessing weekly prophylaxis dosing regimens of octocog alfa (Kovaltry®/BAY 81-8973) used in standard clinical practice in patients with moderate-to-severe haemophilia A.

Von Willebrand Factor Multimer Analysis and Classification: A Comprehensive Review and Updates

Von Willebrand factor (VWF) is a multimeric glycoprotein with essential roles in primary hemostasis. Patients with von Willebrand disease (VWD), due to quantitative and/or qualitative defects of VWF usually experience mucocutaneous bleeding.

Emicizumab: a novel drug in hemophilia A prophylaxis - a narrative review

Hemophilia A is a genetically conditioned disease leading to hemostatic disorders due to factor VIII (FVIII) deficiency. The treatment of hemophilia has evolved throughout the past years and has significantly changed. One of the newest drugs for prophylactic treatment is the humanized bispecific IgG antibody - emicizumab, which binds with factor IXa and factor X, bridging those factors and thus mimicking the activity of factor VIII.

Accessibility and visibility of genetic testing for haemophilia across Europe: Where do we stand?

Haemophilia is characterized by bleeding complications resulting from clotting factor VIII (FVIII) or IX (FIX) deficiency. Identifying the causal pathogenic genetic variant denotes a vital aspect of haemophilia management.

Theory of change and strategic priorities of the world federation of haemophilia

The World Federation of Haemophilia (WFH) is a global network of national member organizations (NMOs) that advocate, collectively and individually, to improve lives of people with inherited bleeding disorders. The WFH vision of "Treatment for All" speaks to a future in which all people with an inherited bleeding disorder will have access to care, regardless of their gender or where they live.

Prophylaxis use of clotting factor replacement products in people with non-severe haemophilia: A review of the literature

People with non-severe haemophilia appear to be under-treated in many countries, and this may lead to joint damage and worsen quality of life. AIM: To review literature for clotting factor replacement prophylaxis in people with non-severe haemophilia A and B (HA/HB) in relation to long-term outcomes to support clinical decision-making.

Early-stage clinical trials for the treatment of Hemophilia A

Hemophilia A is a severe bleeding disorder affecting about 1 in 5,000 males. The gold standard for prophylaxis and treatment of acute bleeding has been factor (F) VIII concentrate. A multitude of treatment modalities are now available and under clinical investigation.

Factor IX inhibitors in haemophilia B: A report of National Haemophilia Registry in China

The development of inhibitors against factor FIX (FIX) is the most serious complication of FIX replacement therapy in haemophilia B (HB) patients. Currently, only few cohorts of HB inhibitor patients have been reported worldwide.

need to increase von Willebrand disease awareness: vwdtest.com – A global initiative to help address this gap

Von Willebrand disease (VWD) is an inherited bleeding disorder caused by quantitative or qualitative deficiencies in von Willebrand factor (VWF). People with VWD may experience excessive, recurrent or prolonged bleeding, particularly during menstruation, childbirth, surgery or following trauma.

Increased acute care utilization, comorbidities and mortality in adults with haemophilia: A population-based cohort study from 2012 to 2019

Improvements in treatment strategies have led to increased life expectancy of persons with haemophilia (PWH). Consequently, age-related comorbidities become increasingly relevant.

Treatment of chronic inflammatory demyelinating polyneuropathy

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a chronic peripheral polyneuropathy that results in disability through immune-mediated nerve injury, but which not uncommonly has residual and irreversible neurological deficits after the active inflammatory component of the disorder has been treated.

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Fibrinogen supplementation for the trauma patient: Should you choose fibrinogen concentrate over cryoprecipitate?

Trauma-induced coagulopathy is frequently associated with hypofibrinogenemia. Cryoprecipitate (Cryo), and fibrinogen concentrate (FC) are both potential means of fibrinogen supplementation. The aim of this study was to compare the outcomes of traumatic hemorrhagic patients who received fibrinogen supplementation using FC versus Cryo.

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Congenital (hypo-)dysfibrinogenemia and bleeding: A systematic literature review

Ranging from bleeding to thrombosis, the clinical features of congenital fibrinogen qualitative disorders, including dysfibrinogenemia and hypodysfibrinogenemia, are highly heterogeneous. Although the associations between some specific fibrinogen mutations and the thrombotic phenotypes have been well elucidated, the underlying mechanism between fibrinogen variants and bleeding events remains underestimated.

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Preoperative fibrinogen level and postcardiac surgery morbidity and mortality rates

High preoperative fibrinogen levels are associated with reduced bleeding rates after cardiac surgery. Fibrinogen is directly involved in inflammatory processes and is a cardiovascular risk factor. Whether high fibrinogen levels before cardiac surgery are a risk factor for mortality or morbidity remains unclear.

2022

JULI

Eptacog beta efficacy and safety in the treatment and control of bleeding in paediatric subjects (<12 years) with haemophilia A or B with inhibitors

Eptacog beta is a new recombinant activated human factor VII bypassing agent approved in the United States for the treatment and control of bleeding in patients with haemophilia A or B with inhibitors 12 years of age or older. AIM: To prospectively assess in a phase 3 clinical trial (PERSEPT 2) eptacog beta efficacy and safety for treatment of bleeding in children <12 years of age with haemophilia A or B with inhibitors.

Phase 1–2 Trial of AAVS3 Gene Therapy in Patients with Hemophilia B

FLT180a (verbrinacogene setparvovec) is a liver-directed adeno-associated virus (AAV) gene therapy that uses a synthetic capsid and a gain-of-function protein to normalize factor IX levels in patients with hemophilia B.

Real-world data on emicizumab prophylaxis in the Milan cohort

We conducted an observational study enrolling 21 consecutive patients with severe haemophilia A (HA) with and without inhibitors, regularly followed at the Angelo Bianchi Bonomi Hemophilia Center of Milan and switched to emicizumab prophylaxis in the post-licensing period after April 2020.

Factor XI deficiency: About 20 cases and literature review

Factor XI deficiency is a rare coagulation disorder with variable bleeding manifestations. AIM: To evaluate the correlation between the degree of factor XI deficiency and the clinical expression of the disease.

Phenotypic and genetic characterizations of the Milan cohort of von Willebrand disease type 2

von Willebrand disease (VWD) type 2 is caused by qualitative abnormalities of von Willebrand factor (VWF). This study aimed to determine the genotypic and phenotypic characterizations of a large VWD type 2 cohort from Milan.

Supporting patients with haemophilia in a world of crises: new role for the WFH and its partners

The last few decades have been marked by major advances for people with haemophilia. They concern the understanding of the mechanisms, diagnosis, treatment and care of clotting factor VIII and IX deficiencies and other inherited bleeding disorders.

Management of haemophilia A with inhibitors: A regional crosstalk

The development of inhibitors with factor VIII (FVIII) replacement therapy is one of the most common and challenging complications of haemophilia A (HA) treatment, jeopardizing treatment efficacy and predisposing patients to high risks of morbidity and mortality. The management of patients with inhibitors is particularly challenging in countries where resources are limited.

A review of the pharmacokinetics, efficacy, and safety of high-purity factor X for the prophylactic treatment of hereditary factor X deficiency

Hereditary factor X (FX) deficiency (FXD) is a rare autosomal recessive bleeding disorder. Plasma-derived FX (pdFX) is a high-purity FX concentrate approved in the United States and Europe for the treatment and prophylaxis of bleeding episodes and for peri-operative management in patients with hereditary FXD (HFXD).

Occupational integration of adults with severe haemophilia (INTHEMO): A study based on the FranceCoag registry

Health of people with severe haemophilia (PwSH) improves thanks to the advancements in haemophilia care, giving them more opportunities in occupational integration. However, there is little literature on the occupational integration of PwSH.

The Impact of Recombinant Versus Plasma-Derived Factor VIII Concentrates on Inhibitor Development in Previously Untreated Patients with Hemophilia A: A 2021 Update of a Systematic Review and Meta-Analysis

Hemophilia A, the most common hereditary disorder, is caused by clotting factor deficiency. Challenges encountered in the current treatment of hemophilia A [factor VIII (FVIII) replacement therapy] due to inhibitor development have caused ineffective treatment as well as morbidity and mortality among patients.

Factor IX antibodies and tolerance in hemophilia B in the Nordic countries - The impact of F9 variants and complications

The development of inhibitory antibodies (inhibitors) in persons with hemophilia B (PwHB) causes significant morbidity. Data on the impact of the F9 variant and immune tolerance induction (ITI) outcome are limited. The aim of this study was to investigate the presence of neutralizing and non-neutralizing antibodies (NNA) in severe hemophilia B (HB) and to evaluate ITI outcome and complications in relation to the pathogenic F9 variant.

Seroprevalence to adeno-associated virus type 6 in people with hemophilia B from a UK adult cohort

Gene therapy shows promise as a potential “cure” for hemophilia A and B. Adeno-associated virus (AAV) vectors are the leading platform to deliver modified genetic code of factor VIII or IX to the liver effecting endogenous production.

Sixth Åland Island Conference on von Willebrand disease

The sixth Åland Islands Conference on von Willebrand disease (VWD) on the Åland Islands, Finland, was held from 20 to 22 September 2018. AIM: The meeting brought together experts in the field of VWD from around the world to share the latest advances and knowledge in VWD.

Immunoglobulin shortage: Practice modifications and clinical outcomes in a reference centre

Growing numbers of indications for intravenous immunoglobulins (IVIg) in recent years has resulted in an increase in the consumption of these products. A lack of raw material has led to IVIg shortage. The objective of this work was to evaluate the impact of this situation on patient care in one French referral centre considering practice modifications and clinical impact.

Role of Fc Core Fucosylation in the Effector Function of IgG1 Antibodies

The presence of fucose on IgG1 Asn-297 N-linked glycan is the modification of the human IgG1 Fc structure with the most significant impact on FcɣRIII affinity.

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Advances in Fibrin-Based Materials in Wound Repair: A Review

The first bioprocess that occurs in response to wounding is the deterrence of local hemorrhage. This is accomplished by platelet aggregation and initiation of the hemostasis cascade. The resulting blood clot immediately enables the cessation of bleeding and then functions as a provisional matrix for wound healing, which begins a few days after injury.

2022

JUNI

Factor XI Inhibition for the Prevention of Venous Thromboembolism: An Update on Current Evidence and Future perspectives

During the past decade, emergence of direct oral anticoagulants (DOACs) has drastically improved the prevention of thrombosis. However, several unmet needs prevail in the field of thrombosis prevention, even in the DOACs’ era.

Relationship between bleeding episodes, health-related quality of life and direct costs in adults with severe haemophilia A: Secondary analyses from the CHESS study

To the Editors, The prevalence of significant morbidities and the high cost of care associated with severe haemophilia A contribute to both impaired health-related quality of life (HRQoL) for patients and significant financial impact on healthcare budgets.

Comparative biochemical efficacy analysis of an alpha1-proteinase inhibitor (Glassia (R)) in patients with alpha-1 antitrypsin deficiency

Alpha1-proteinase inhibitor (A1PI) augmentation is the only specific treatment targeting the underlying deficiency in alpha1-antitrypsin deficiency (AATD).

Structural Insights into Blood Coagulation Factor VIII: Procoagulant Complexes, Membrane Binding, and Antibody Inhibition

Advances in structural studies of blood coagulation factor VIII (FVIII) have provided unique insight into FVIII biochemistry.

Hemophilia A: Strategies for Improving Long-Term Holistic Management, Adherence, and Quality of Life

Hemophilia A is a rare inherited bleeding disorder characterized by a deficiency in factor VIII.

Hemophilia A/B

Adeno-associated virus (AAV)-mediated gene transfer has successfully raised, and in some cases transiently normalized, FVIII or FIX activity levels in adults with severe hemophilia.

Real-World Clinical Outcomes and Replacement Factor VIII Consumption in Patients with Haemophilia A in Italy: A Comparison between Prophylaxis Pre and Post Octocog Alfa (BAY 81-8973)

new generations of rFVIII products offered the possibility to improve personalized therapeutic approaches, reducing the number of infusions or increasing the protection against bleeding risk. The aim of this study was to assess the effectiveness of prophylaxis with BAY 81-8973 (octocog alfa, Kovaltry(®), Bayer Pharma AG) in the real-world setting and its impact on FVIII consumption compared to previous standard half-life treatments.

Efficient and Sustainable Platform for Preparation of a High-Quality Immunoglobulin G as an Urgent Treatment Option During Emerging Virus Outbreaks

During the pre-vaccine era of the COVID-19 pandemic convalescent plasma has once again emerged as a major potential therapeutic form of passive immunization that in specific cases still represents irreplaceable treatment option.

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Evaluation of Plasma Fibrinogen Levels before and after Coronary Artery Bypass Graft Surgery and Its Association with the Need for Blood Products

The present study investigated the plasma level of fibrinogen before and after removing the pump in coronary artery bypass graft (CABG) surgery and its relationship with the need for blood products.

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Impact of cardiopulmonary bypass duration on efficacy of fibrinogen replacement with cryoprecipitate compared with fibrinogen concentrate: a post hoc analysis of the Fibrinogen Replenishment in Surgery (FIBRES) randomised controlled trial

Coagulopathy in cardiac surgery is frequently associated with acquired hypofibrinogenaemia, which can be treated with either purified fibrinogen concentrate (FC) or cryoprecipitate. Because the latter is not purified and therefore contains additional coagulation factors, it is thought to be more effective for treatment of coagulopathy that occurs after prolonged cardiopulmonary bypass (CPB). We examined the impact of CPB duration on the efficacy of the two therapies in cardiac surgery.

2022

MEI

Safety of eptacog beta: Comparing the 225 μg/kg and 75 μg /kg dosing regimens across pivotal clinical trials

No abstract available

Emicizumab state-of-the-art update

Emicizumab is a bispecific monoclonal antibody developed to address the unmet needs of clotting factor replacement therapy and has become the benchmark for optimal prophylaxis in managing patients with haemophilia A with inhibitors. We describe the emicizumab rollout and pharmacokinetic strategies and their use in paediatric patients.

Acquired bleeding disorders

Acquired bleeding disorders can accompany hematological, neoplastic, autoimmune, cardiovascular or liver diseases, but can sometimes also arise spontaneously. They can manifest as single factor deficiencies or as complex hemostatic abnormalities.

von Willebrand disease and von Willebrand factor

Progress in both basic and translational research into the molecular mechanisms of VWD can be seen in multiple fields.

A Rare Case of Acquired Hemophilia A in Adolescents and Young Adults

Acquired hemophilia A (AHA) is a rare bleeding disorder, especially in adolescents and young adults (AYAs) attributable to the development of autoantibodies against coagulation factor VIII (FVIII).

Managing invasive procedures in haemophilia patients with limited resources, extended half-life concentrates or non-replacement therapies in 2022

New treatment possibilities and modalities are now available globally for patients with haemophilia requiring surgery or invasive procedures.

Towards novel treatment options in von Willebrand disease

Deficiency or dysfunction of von Willebrand factor (VWF) is associated with a bleeding disorder known as von Willebrand disease (VWD).

Does difference between label and actual potency of factor VIII concentrate affect pharmacokinetic-guided dosing of replacement therapy in haemophilia A?

To account for interindividual variability in the pharmacokinetics (PK) of factor concentrates, PK-guided dosing is increasingly implemented in haemophilia patients. Calculations are based on provided label potency, but legislation allows a potency difference of +/- 20% between label and actual potency. It is unknown if these differences affect PK guidance.

Pharmacokinetic modeling and simulation of subcutaneous and intravenous IgG dosing in patients with primary immunodeficiency diseases

A population pharmacokinetic (PK) model for comparing the PK of subcutaneously administered immunoglobulin G (IgG) replacement therapy (SCIG) with Gamunex-C 10% or SCIG 20% formulations in patients with primary immunodeficiency diseases was developed using data from 3 clinical trials (N = 95, 69.5% adults, 30.5% < 18 years) of intravenous IG (IVIG) 10% and SCIG 10% or SCIG 20%.

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Use of Hyperoncotic Human Albumin Solution in Severe Traumatic Brain Injury Revisited—A Narrative Review and Meta-Analysis

A significant proportion of patients with a severe traumatic brain injury (TBI) have hypoalbuminemia and require fluid resuscitation. Intravenous fluids can have both favorable and unfavorable consequences because of the risk of hyperhydration and hypo-or hyperosmolar conditions, which may affect the outcome of a TBI.

2022

APRIL

Emicizumab enhances thrombus formation in vitro under high shear flow conditions in whole blood from patients with type 1 and type 3 von Willebrand disease

Type 1 and type 3 von Willebrand disease (VWD) are caused by partial and complete, quantitative deficiency of von Willebrand factor (VWF), respectively, and factor (F)VIII/VWF complex concentrates are used for haemostatic treatment. Emicizumab, mimics activated FVIII, reduces bleeding in haemophilia A patients. The effects of emicizumab on haemostasis in both types of VWD remain to be fully established, however.

Effectiveness of long-term prophylaxis using pdFVIII/VWF concentrate in patients with inherited von Willebrand disease

Patients with symptomatic von Willebrand disease (VWD) should be offered long-term prophylaxis (LTP) to prevent recurrent bleedings. Our objective was to evaluate the effectiveness and safety of Voncento®, a plasma derived FVIII/VWF concentrate (ratio 1:2.4), administrated in LTP.

Enhanced pharmacokinetics and reduced bleeds in boys with hemophilia A after switching to Kovaltry from other standard half-life factor VIII concentrates

BAY81-8973 (Kovaltry; Bayer, Berkeley, CA, USA) was reported with enhanced pharmacokinetic (PK) profiles compared with some other standard half-life (SHL) factor VIII (FVIII) concentrates. Limited head-to-head comparative studies were conducted in a real-world setting. Objective: To make head-to-head comparisons of PK and clinical outcomes between Kovaltry and three other SHL FVIII concentrates.

Alpha-1 antitrypsin deficiency: A re-surfacing adult liver disorder

Alpha-1 antitrypsin deficiency (AATD) arises from mutations in the SERPINA1 gene encoding alpha-1 antitrypsin (AAT) that lead to AAT retention in the endoplasmic reticulum of hepatocytes, causing proteotoxic liver injury and loss-of-function lung disease.

International guidelines regarding the role of IVIG in the management of Rh- and ABO-mediated haemolytic disease of the newborn

Haemolytic disease of the newborn (HDN) can be associated with significant morbidity. Prompt treatment with intensive phototherapy (PT) and exchange transfusions (ETs) can dramatically improve outcomes. ET is invasive and associated with risks. Intravenous immunoglobulin (IVIG) may be an alternative therapy to prevent use of ET.

Association of Maintenance Intravenous Immunoglobulin With Prevention of Relapse in Adult Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease

Recent studies suggest that maintenance intravenous immunoglobulin (IVIG) may be an effective treatment to prevent relapses in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD); however, most of these studies had pediatric cohorts, and few studies have evaluated IVIG in adult patients.

Long-term safety of facilitated subcutaneous immunoglobulin treatment in pregnant women with primary immunodeficiency diseases: results from a registry study

Clinical outcomes of women who become pregnant during/after facilitated subcutaneous immunoglobulin (fSCIG) treatment are not well characterized.

2022

FEBRUARI

Managing Severe Hemophilia A in Children: Pharmacotherapeutic Options

Hemophilia A is the most common severe inherited bleeding disorder in males. Initial treatment strategies focused on the use of factor concentrates to prevent joint bleeding and the development of long-term crippling arthropathy.

Immunoglobulin Replacement Therapy in Chronic Lymphocytic Leukaemia patients with hypogammaglobulinaemia and infection

OBJECTIVES: To analyse total national utilisation of immunoglobulin (Ig) replacement therapy (IgRT) for Chronic Lymphocytic Leukaemia patients with acquired hypogammaglobulinaemia and severe and/or recurrent bacterial infections.

Subcutaneous immunoglobulin use in immunoglobulin-naive patients with primary immunodeficiency: a systematic review

Identify and describe published literature on the use of subcutaneous immunoglobulin (SCIG) as initial immunoglobulin (IG)-replacement therapy for patients with primary immunodeficiency diseases (PID).

Withdrawal of intravenous immunoglobulin in chronic inflammatory demyelinating polyradiculoneuropathy

Intravenous immunoglobulins (IVIg) are an efficacious treatment for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Biomarkers for disease activity are lacking, making the need for ongoing treatment difficult to assess, leading to potential overtreatment, and high health care costs.

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Real-life experiences with goal-directed prohemostatic therapy with fibrinogen concentrate, prothrombin complex concentrate, and recombinant factor VIIa: a retrospective study of 287 consecutive patients

The Danish Capital Region Blood Bank operates a 24/7 on-call service staffed with physicians specialized in hemostatic management to guide clinicians in hemostatic resuscitation, including administration of prohemostatic therapy (PHT). The outcome of patients who receive PHT as part of hemostatic resuscitation remains unanswered. The objective of this study was therefore to investigate clinical outcome of patients receiving PHT managed by the on-call service.

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Optimizing fresh-frozen plasma transfusion in surgical neonates through thromboelastography: a quality improvement study

Fresh frozen plasma (FFP) is largely misused in the neonatal setting. The aim of the study is to evaluate the impact of a Thromboelastography (TEG)-based Quality Improvement (QI) project on perioperative FFP use and neonatal outcomes.

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Early cryoprecipitate transfusion versus standard care in severe postpartum haemorrhage: a pilot cluster-randomized trial

There is a lack of evidence evaluating cryoprecipitate transfusion in severe postpartum haemorrhage. We performed a pilot cluster-randomized controlled trial to evaluate the feasibility of a trial on early cryoprecipitate delivery in severe postpartum haemorrhage.

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Heterogeneity of Genotype-Phenotype in Congenital Hypofibrinogenemia-A Review of Case Reports Associated with Bleeding and Thrombosis

Congenital fibrinogen disorders are diseases associated with a bleeding tendency; however, there are also reports of thrombotic events.

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Postoperative bleeding complications in patients with hemophilia undergoing major orthopedic surgery: A prospective multicenter observational study

This multicenter, prospective, observational cohort study evaluated the rate of bleeding during the postoperative period after total hip (THA) or knee arthroplasty (TKA).

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Rotational thromboelastometry in children presenting to an Australian major trauma centre: A retrospective cohort study

This retrospective cohort study aims to describe patterns of rotational thromboelastometry (ROTEM™) results in paediatric trauma following the implementation of a ROTEM-guided critical bleeding algorithm and major haemorrhage protocol (MHP).

Type 2B von Willebrand Disease in Pregnancy: A Systematic Literature Review

Our objective was to review the maternal characteristics and obstetric complications in women with type 2B von Willebrand disease (VWD). A systematic literature search was conducted using PubMed, Scopus, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov.

Hemophilia: A Review of Perioperative Management for Cardiac Surgery

Hemophilia is an X-linked, recessive bleeding disorder. Improvements in factor replacement therapy and overall approach to hemophilia management have increased the lifespan and quality of life for patients with hemophilia.

Clinical Efficacy and Safety of Fanhdi®, a Plasma-Derived VWF/Factor VIII Concentrate, in von Willebrand Disease in Spain: A Retrospective Study

OBJECTIVE: To evaluate the efficacy and safety of a plasma-derived factor VIII concentrate containing von Willebrand Factor (pdVWF/FVIII) in standard clinical practice in von Willebrand Disease (VWD) patients.

Report of surgeries, their outcome, and the thrombin generation assay in patients with Factor XI deficiency: A retrospective single-centre study

In patients with FXI deficiency, the risk of surgery-related bleeding is poorly correlated with plasma FXI activity (FXI:C); the latter can therefore not be used as a reliable predictor of bleeding in surgeries.

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Practical Aspects of Transitioning from Intravenous to Subcutaneous Immunoglobulin Therapy in Neuromuscular Disorders

Recent evidence shows that subcutaneous immunoglobulin (SCIG) is as efficacious as intravenous immunoglobulin (IVIG) and has a better safety profile and acceptance rate among patients with neuromuscular disorders who require maintenance IVIG treatment.

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Mutations Accounting for Congenital Fibrinogen Disorders: An Update

Fibrinogen is a complex protein that plays a key role in the blood clotting process. It is a hexamer composed of two copies of three distinct chains: A alpha, B beta, and gamma encoded by three genes, FGA, FGB , and FGG, clustered on the long arm of chromosome 4.

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Impact of fibrinogen infusion on thrombin generation and fibrin clot structure in patients with inherited afibrinogenemia

Inherited afibrinogenemia is a very rare disease characterized by complete absence of fibrinogen in the circulation and an increased risk in both thrombosis and bleeding. Infusion of fibrinogen concentrate (FC) is the main approach for prevention and management of bleeding; however, it has been reported to carry a thrombotic risk.

2022

JANUARI

In Vitro Comparison of Recombinant and Plasma-Derived von Willebrand Factor Concentrate for Treatment of Acquired von Willebrand Syndrome in Adult Extracorporeal Membrane Oxygenation Patients

Coagulopathic bleeding is common during adult extracorporeal membrane oxygenation (ECMO) and acquired von Willebrand syndrome is a contributing factor. We compared ECMO patient blood samples that were treated in vitro with recombinant von Willebrand Factor concentrate and plasma-derived von Willebrand Factor concentrate.

The 2021 von Willebrand disease guidelines: Clarity and controversy

Medicine is rapidly developing, and publications are produced at an enormous rate making it impossible for a single individual to remain up to date in all areas. As result, clinical guidelines utilizing all the evidence are now available in almost all areas of medicine.

Type 2B von Willebrand Disease: Early Manifestation as Neonatal Thrombocytopenia

Here, we report about a preterm female newborn with a prolonged course of severe thrombocytopenia and hematomas.

Bone mineral density in haemophilia - a multicenter study evaluating the impact of different replacement regimens

The aim of this study was to investigate if prophylactic treatment in severe haemophilia impact on bone mineral densisty (BMD) in adults with haemophilia A/B.

Real-World Rates of Bleeding, Factor VIII Use, and Quality of Life in Individuals with Severe Haemophilia A Receiving Prophylaxis in a Prospective, Noninterventional Study

Regular prophylaxis with exogenous factor VIII (FVIII) is recommended for individuals with severe haemophilia A (HA), but standardized data are scarce. Here, we report real-world data from a global cohort.

FVIII at the crossroad of coagulation, bone and immune biology: Emerging evidence of biological activities beyond hemostasis

Hemophilia A is an X-linked hereditary disorder that results from deficient coagulation factor VIII (FVIII) activity, leading to spontaneous bleeding episodes, particularly in joints and muscles.

Haemophilia in France: Modulization of the Clinical Pathway for Patients

Process-of-care studies participate in improving the efficiency of the care pathway for patient with haemophilia (CPPH) and rationalize the multidisciplinary management of patients. Our objective is to establish a current overview of the different actors involved in the management of patients with haemophilia and to provide an accurate description of the patient trajectory.

Tailored prophylaxis in children with severe hemophilia: A four-year Iranian study

Prophylaxis -the current standard care for patients with severe hemophilia -should be planned to optimize the replacement therapy and minimize bleeding. We report our single-center experience of tailored prophylaxis in children affected by hemophilia A (HA) and hemophilia B.

Intravenous immunoglobulin for inflammatory demyelinating polyneuropathy

Intravenous immunoglobulin (IVIg) plays a key role in treatment of inflammatory demyelinating polyneuropathies such as Guillain–Barre syndrome (GBS).

Frequency and clinical correlates of anti-nerve antibodies in a large population of CIDP patients included in the Italian database

To investigate the frequency and clinical correlates of anti-nerve autoantibodies in an unselected series of Italian patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP).

Overview of subcutaneous immunoglobulin 16.5% in primary and secondary immunodeficiency diseases

Primary immunodeficiency diseases, and select secondary immunodeficiency diseases, weaken the immune system, allowing infections and other health problems to occur more easily.

Immunoglobulin for multifocal motor neuropathy

Multifocal motor neuropathy (MMN) is a rare, probably immune-mediated disorder characterized by slowly progressive, asymmetric, distal weakness of one or more limbs with no objective loss of sensation. It may cause prolonged periods of disability. Treatment options for MMN are few.

Evans syndrome in adults: an observational multicenter study

Evans syndrome (ES) is a rare condition, defined as the presence of 2 autoimmune cytopenias, most frequently autoimmune hemolytic anemia and immune thrombocytopenia (ITP) and rarely autoimmune neutropenia.

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Impact of Early, Low-Dose Factor VIIa on Subsequent Transfusions and Length of Stay in Cardiac Surgery

Recombinant factor VII (rFVIIa) is used to treat cardiac surgical bleeding in an off-label manner. However, optimal dosing and timing of administration to provide efficacious yet safe outcomes remain unknown.

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Efficacy and safety of fibrinogen concentrate for on‐demand treatment of bleeding and surgical prophylaxis in paediatric patients with congenital fibrinogen deficiency

Congenital fibrinogen deficiency (CFD) is a rare, inherited disorder affecting normal blood clotting function, where patients can experience severe and/or frequent bleeding episodes (BEs). Treatment with human fibrinogen concentrate (HFC) can prevent/arrest bleeding. There is a need for more data on the efficacy, pharmacokinetics (PK) and safety of HFC treatment in paediatric patients with CFD.

2021

DECEMBER

Hemophilia gene therapy: ushering in a new treatment paradigm?

After 3 decades of clinical trials, repeated proof-of-concept success has now been demonstrated in hemophilia A and B gene therapy.

Clinical, humanistic, and economic burden of severe haemophilia B in adults receiving factor IX prophylaxis: findings from the CHESS II real-world burden of illness study in Europe

Background Real-world studies of the burden of severe haemophilia B in the context of recent therapeutic advances such as extended half-life (EHL) factor IX (FIX) products are limited. We analysed data from the recent CHESS II study to better understand the clinical, humanistic, and economic burden of severe haemophilia B in Europe.

Infection rates and tolerability of three different immunoglobulin administration modalities in patients with primary immunodeficiency diseases

This post hoc analysis evaluated the efficacy and overall tolerability of immunoglobulin (Ig) treatment modalities (intravenous Ig [iv.Ig], subcutaneous Ig [sc.Ig] and facilitated sc.Ig [fsc.Ig]).

Economic evaluation of subcutaneous versus intravenous immunoglobulin therapy in chronic inflammatory demyelinating polyneuropathy: a real-life study

Chronic inflammatory demyelinating polyneuropathy (CIDP) is an acquired peripheral neuropathy of immunological origin with a clinical presentation and course that are extremely variable.

3D Structures of IgA, IgM, and Components

Immunoglobulin G (IgG) is currently the most studied immunoglobin class and is frequently used in antibody therapeutics in which its beneficial effector functions are exploited. IgG is composed of two heavy chains and two light chains, forming the basic antibody monomeric unit.

Secondary failure: immune responses to approved protein therapeutics

Recombinant therapeutic proteins are a broad class of biological products used to replace dysfunctional human proteins in individuals with genetic defects (e.g., factor VIII for hemophilia) or, in the case of monoclonal antibodies, bind to disease targets involved in cancers, autoimmune disorders, or other conditions.

Effectiveness and Safety of an Intravenous Immune Globulin (IVIG) Preparation in Post-exposure Prophylaxis (PEP) Against Measles in Infants

Administration of measles virus (MV)-specific IgG as post-exposure prophylaxis (PEP) is known to effectively prevent measles. Since the introduction of active immunization against measles, the levels of MV-specific IgG antibodies in the population have dropped.

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Haematological parameters associated with postpartum haemorrhage after vaginal delivery: Results from a French cohort study

Immediate postpartum haemorrhage (PPH) is a major, feared and often unpredictable issue. Besides many clinical risk factors, some biological parameters could also be predictive of PPH.

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Postpartum Hemorrhage in Patients with Type 1 von Willebrand Disease: A Systematic Review

Type 1 von Willebrand disease (VWD) is the most common subtype of VWD, comprising 75% of VWD patients. We provide a systematic review of type 1 VWD in pregnancy. Our objective was to evaluate the rate of postpartum hemorrhage (PPH) in patients with known type 1 VWD.

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Unusual pattern of thrombotic events in young adult non-critically ill patients with COVID-19 may result from an undiagnosed inherited and acquired form of thrombophilia

In 145 previously healthy non-critically ill young adults, coronavirus disease 2019 (COVID-19)-related symptoms, risk factors for thrombosis, coagulation and inflammatory parameters were compared, with 29 patients reporting unusual thrombotic events (UTEs) and 116 not having thrombotic events.

2021

OKTOBER

PERSEPT 3: A phase 3 clinical trial to evaluate the haemostatic efficacy of eptacog beta (recombinant human FVIIa) in perioperative care in subjects with haemophilia A or B with inhibitors

Surgical procedures in persons with haemophilia A or B with inhibitors (PwHABI) require the use of bypassing agents (BPA) and carry a high risk of complications. Historically, only two BPAs have been available; these are reported to have variable responses.

Emicizumab prophylaxis in infants with severe haemophilia A without inhibitors: Illustrative real-world cases to support shared decision-making

Emicizumab has been shown to be safe and effective for prevention of bleeds in patients with severe haemophilia A (SHA), both with and without inhibitors.

Prophylaxis in children with haemophilia in an evolving treatment landscape

For children with haemophilia, early initiation of prophylaxis is crucial to prevent life-threatening bleeds and maintain joint health throughout life.

Emerging drugs for hemophilia A: insights into phase II and III clinical trials

Hemophilia is a lifelong, genetic bleeding disorder, which inadequately treated results in permanent joint damage. It is characterized by spontaneous and trauma-related bleeding episodes.

The Role of Plasma Exchange in the Treatment of Refractory Autoimmune Neurological Diseases: a Narrative Review

Autoimmune neurological disorders are commonly treated with immunosuppressive therapy. In patients with refractory conditions, standard immunosuppression is often insufficient for complete recovery or to prevent relapses.

Treatments for HBV: A Glimpse into the Future

The hepatitis B virus is responsible for most of the chronic liver disease and liver cancer worldwide.

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Factor XIII Deficiency: A Review of Clinical Presentation and Management

Factor XIII (FXIII) deficiency is a rare autosomal recessive disorder that can result in life-threatening bleeding and early fetal loss.

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Comments on 'U-shaped relationship between preoperative plasma fibrinogen levels and severe peri-operative bleeding in cardiac surgery: A report from the Perioperative Events aSSessment in Adult Cardiac surgery (PESSAC) registry' by Mion et al.

Editor, We read with great interest the article entitled ‘U-shaped relationship between preoperative plasma fibrinogenlevels and severe peri-operative bleeding in cardiac surgery: A report from the Perioperative Events aSSessment in Adult Cardiac surgery (PESSAC) registry’.

2021

SEPTEMBER

Low immunogenicity of emicizumab in persons with haemophilia A

Emicizumab is a humanised, bispecific monoclonal antibody mimicking the cofactor function of activated factor (F)VIII. It is indicated for routine prophylaxis of bleeding episodes in persons with haemophilia A (PwHA) with/without FVIII inhibitors.

Advances in the management of haemophilia: emerging treatments and their mechanisms

Mainstay haemophilia treatment, namely intravenous factor replacement, poses several clinical challenges including frequent injections due to the short half-life of recombinant factors, intravenous administration (which is particularly challenging in those with difficult venous access), and the risk of inhibitor development.

Recombinant factor VIIa for hemorrhagic stroke treatment at earliest possible time (FASTEST): Protocol for a phase III, double-blind, randomized, placebo-controlled trial

Intracerebral hemorrhage is the deadliest form of stroke. Hematoma expansion, growth of the hematoma between the baseline computed tomography scan and a follow-up computed tomography scan at 24 ± 6 h, predicts long-term disability or death.

Hemophilia A and C in a female: The first case report in literature

One of the relatively rare hemostatic disorders is coagulation factors’ deficiency, where a single factor or multiple factors can be deficient. All hereditary coagulation factors’ deficiencies are autosomal recessive, so they can manifest in both genders, but Hemophilia A and B are X-linked disorders.

Recommended Primary Outcomes for Clinical Trials Evaluating Hemostatic Agents in Patients with Intracranial Hemorrhage: A Consensus Statement

In patients with acute spontaneous or traumatic intracranial hemorrhage, early hemostasis is thought to be critical to minimize ongoing bleeding. However, research evaluating hemostatic therapies has been hampered by a lack of standardized clinical trial outcome measures.

Emicizumab in acquired haemophilia A: about two clinical cases and literature review

Acquired haemophilia A (AHA) is a rare and severe haemorrhagic autoimmune disease caused by autoantibodies directed against factor VIII (FVIII). Treatment is based on two principles, including haemostatic control to compensate FVIII inhibition and eradication of inhibiting antibodies using immunosuppressive therapy.

The EHA Research Roadmap: Blood Coagulation and Hemostatic Disorders

In 2016, the European Hematology Association (EHA) published the EHA Roadmap for European Hematology Research (1) aiming to highlight achievements in the diagnostics and treatment of blood disorders, and to better inform European policy makers and other stakeholders about the urgent clinical and scientific needs and priorities in the field of hematology.

Randomized trial of intravenous immunoglobulin maintenance treatment regimens in chronic inflammatory demyelinating polyradiculoneuropathy

Background and purpose: High peak serum immunoglobulin G (IgG) levels may not be needed for maintenance intravenous immunoglobulin (IVIg) treatment in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and such high levels may cause side effects.

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A randomized phase 3 trial evaluating antithrombin gamma treatment in Japanese patients with early-onset severe preeclampsia (KOUNO-TORI study): Study protocol

Preeclampsia is a leading cause of maternal and perinatal morbidity and mortality. Several studies have demonstrated the beneficial effects of antithrombin replacement in patients with preeclampsia.

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Heparin Resistance - Clinical Perspectives and Management Strategies

Heparin Resistance Heparin resistance is suspected when more heparin than usual is needed to achieve a therapeutic range of activated partial-thromboplastin time.

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First-Line Administration of Fibrinogen Concentrate in the Bleeding Trauma Patient: Searching for Effective Dosages and Optimal Post-Treatment Levels Limiting Massive Transfusion—Further Results of the RETIC Study.

Fibrinogen supplementation is recommended for treatment of severe trauma hemorrhage. However, required dosages and aimed for post-treatment fibrinogen levels remain a matter of discussion.

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Rare Defects: Looking at the Dark Face of the Thrombosis

Venous thromboembolism (VTE) constitutes a serious and potentially fatal disease, often complicated by pulmonary embolism and is associated with inherited or acquired factors risk.

2021

JULI

Recent Advances in the Treatment of Hemophilia: A Review

Progress in hemophilia therapy has been remarkable in the first 20 years of the third millennium, but the innovation began with the description the fractionation of plasma in 1946.

Consensus Recommendations for Intramuscular COVID-19 Vaccination in Patients with Hemophilia

Currently available coronavirus disease 2019 (COVID-19) vaccines are approved for intramuscular injection and efficacy may not be ensured when given subcutaneously. For years, subcutaneous vaccination was recommended in patients with hemophilia to avoid intramuscular bleeds. Therefore, recommendations for the application of COVID-19 vaccines are needed.

Fc-Receptor Targeted Therapies for the Treatment of Myasthenia gravis

Myasthenia gravis (MG) is an autoimmune disease in which immunoglobulin G (IgG) antibodies (Abs) bind to acetylcholine receptors (AChR) or to functionally related molecules in the postsynaptic membrane at the neuromuscular junction.

Clinical outcome of CIDP one year after start of treatment: a prospective cohort study

To assess clinical outcome in treatment-naive patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP).

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Administration of Fibrinogen Concentrate Combined with Prothrombin Complex Maintains Hemostasis in Children Undergoing Congenital Heart Repair (A Long-Term Propensity Score-Matched Study)

Bleeding is a common problem in children with congenital heart disease undergoing major cardiac surgery requiring cardiopulmonary bypass (CPB). Little is known about optimal management with blood products.

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Four-Factor Prothrombin Complex Concentrate: An Indispensable Adjunct in Coagulopathy of Trauma Management–A Comparative Review of the Literature over 2 Decades

Damage control resuscitation forms the cornerstone of management in trauma surgery. Several blood products have been widely used for preoperative transfusions prior to emergency surgeries and for hemorrhage control in trauma. Prothrombin complex concentrate (PCC) is now being introduced as an essential component of damage control resuscitation.

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Fibrin(ogen) as a Therapeutic Target: Opportunities and Challenges

Fibrinogen is one of the key molecular players in haemostasis. Thrombin-mediated release of fibrinopeptides from fibrinogen converts this soluble protein into a network of fibrin fibres that form a building block for blood clots. Thrombin-activated factor XIII further crosslinks the fibrin fibres and incorporates antifibrinolytic proteins into the network, thus stabilising the clot.

2021

JUNI

Von Willebrand factor, ADAMTS13 and mortality in dialysis patients

Von Willebrand Factor (VWF) multimers are cleaved into smaller and less coagulant forms by the metalloprotease ADAMTS13. The aim of this study was to investigate the association between VWF and ADAMTS13 and mortality in dialysis patients.

Treatment of alpha-1 antitrypsin deficiency using hepatic-specified cells derived from human-induced pluripotent stem cells

alpha-1 antitrypsin deficiency (AATD) is an inherited liver disease characterized by the "Z" mutations, which can cause pulmonary emphysema and liver fibrosis. Transplantation of the organ (i.e., the lung/liver) is the best treatment method, however, the scarcity of suitable donors limits its application.

Haemophilia

Haemophilia A and B are rare congenital, recessive X-linked disorders caused by lack or deficiency of clotting factor VIII (FVIII) or IX (FIX), respectively.

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Fibrinogen in traumatic haemorrhage

Recent advances in the understanding of the pathophysiological processes associated with traumatic haemorrhage and trauma-induced coagulopathy (TIC) have resulted in improved outcomes for seriously injured trauma patients. However, a significant number of trauma patients still die from haemorrhage.

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There May Not Be a Definite Winner, But Fibrinogen Concentrate is Clearly a Factor to Be Reckoned With

Acquired hypofibrinogenemia after cardiopulmonary bypass (CPB) is a common phenomenon and is likely an important contributor to the complex coagulopathy inherent in cardiac surgery.

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Management of a High-Risk Surgery with Emicizumab and Factor VIII in a Child with a Severe Hemophilia A and Inhibitor

The recent development of a humanized, bi-specific, and monoclonal antibody mimicking the function of activated factor VIII was a revolution in the management of patients suffering from severe hemophilia A with inhibitors.

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Pro-Con Debate: Fibrinogen Concentrate or Cryoprecipitate for Treatment of Acquired Hypofibrinogenemia in Cardiac Surgical Patients

Cryoprecipitate has been the gold standard for treating acquired hypofibrinogenemia in cardiac surgery for nearly 50 years.

Alpha 1-Antitrypsin deficiency in liver explants in a Mexican cohort: A unique cohort to assess the role of heterozygous genotypes in liver disease

Alpha 1-Antitrypsin (AAT) deficiency (AATD) is an under-recognized and undiagnosed inherited genetic disorder thatinduces chronic liver disease [1,2].

Novel mutation in coagulation factor VII (Carmel mutation): Identification and characterization

Measurement of factor VII (FVII) activity does not enable prediction of bleeding tendency in individuals with inherited FVII deficiency.

Commercial alpha 1-antitrypsin preparations markedly differ in their potential to inhibit the ATP-induced release of monocytic interleukin-1 beta

The acute phase protein alpha 1-antitrypsin (AAT) inhibits numerous proteases, specifically neutrophil elastase. Patients with an AAT deficiency due to mutations frequently develop early onset emphysema.

European Academy of Neurology/Peripheral Nerve Society Guideline on diagnosis and treatment of chronic inflammatory demyelinating polyradiculoneuropathy: Report of a joint Task Force — Second Revision

To revise the 2010 consensus guideline on chronic inflammatory demyelinating polyradiculoneuropathy (CIDP).

Intravenous immunoglobulin treatment for patients with severe COVID-19: a retrospective multi-center study

Intravenous immunoglobulin (IVIG) is commonly used to treat severe COVID-19, although the clinical outcome of such treatment remains unclear. This study evaluated the effectiveness of IVIG treatment in severe COVID-19 patients.

Immediate high-dose intravenous immunoglobulins followed by direct thrombin-inhibitor treatment is crucial for survival in Sars-Covid-19-adenoviral vector vaccine-induced immune thrombotic thrombocytopenia VITT with cerebral sinus venous and portal vein thrombosis.

Here, we report a case of a 29-year-old male public healthcare professional, vaccinated with the recombinant adenoviral vector encoding the spike protein antigen of SARSCoV-2 (ChAdOx1 nCov-19, AstraZeneca) on the 29th of March (day 1).

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Fibrinogen in traumatic haemorrhage

Recent advances in the understanding of the pathophysiological processes associated with traumatic haemorrhage and trauma-induced coagulopathy (TIC) have resulted in improved outcomes for seriously injured trauma patients. However, a significant number of trauma patients still die from haemorrhage.

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Fibrinogen prophylaxis for reducing perioperative bleeding in patients undergoing radical cystectomy: A double-blind placebo-controlled randomized trial

Excessive bleeding is an important complication of radical cystectomy. We aimed to assess whether preoperative administration of fibrinogen decreases perioperative bleeding and improves the outcome of radical cystectomy.

2021

MEI

Antithrombin and Its Role in Host Defense and Inflammation

Antithrombin (AT) is a natural anticoagulant that interacts with activated proteases of the coagulation system and with heparan sulfate proteoglycans (HSPG) on the surface of cells. The protein, which is synthesized in the liver, is also essential to confer the effects of therapeutic heparin.

Safety and efficacy of BAY 94-9027, an extended-half-life factor VIII, during minor surgical procedures in patients with severe haemophilia A

In patients with haemophilia A, minor surgical interventions are vital for improving well-being and may prevent major surgical procedures. However, the risk of bleeding in minor surgery may be higher than in major surgery.

Comparative analysis of the pivotal studies of extended half-life recombinant FVIII products for treatment of haemophilia A

The need to reduce the burden of injections and improve adherence and clinical outcomes in haemophilia A led to the development of recombinant FVIII products endowed with an extended plasma half-life (EHL-rFVIII) in comparison with standard half-life products (SHL-rFVIII).

Increased VWF and Decreased ADAMTS-13 in COVID-19: Creating a Milieu for (Micro)Thrombosis

von Willebrand factor (VWF) is a large adhesive multimeric protein involved in hemostasis. The larger the size (or number of VWF multimers), the greater the functionality of the protein. A deficiency or defect of VWF can lead to von Willebrand disease (VWD) and cause bleeding.

Benefits of immunoglobulin substitution in primary and secondary immunodeficiencies: Interim analysis of a prospective, long-term non-interventional study

To assess the safety, tolerability, and effectiveness of the intravenous immunoglobulin (IVIG) Intratect 100 g/L in a prospective, large-scale non-interventional study (NIS) of patients with a wide range of antibody deficiencies as well as other indications for IVIG, risk factors, and frequency of pre-treatments.

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Viscoelastic testing to assess the effects of rapid fibrinogen concentrate administration after cardiopulmonary bypass: insights from the REPLACE study

Haemorrhage during and following surgery results in increased morbidity and mortality. Low plasma fibrinogen levels have been associated with increased blood loss and transfusion requirements. Fibrinogen supplementation has been shown to reduce bleeding in coagulopathic patients.

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Treatment of Bleeding in Patients with Liver Disease

Patients with cirrhosis frequently have complex alterations in their hemostatic system. Although routine diagnostic tests of hemostasis in cirrhosis (platelet count, prothrombin time, fibrinogen level) are suggestive of a bleeding tendency, it is now widely accepted that these tests do not reflect hemostatic competence in this population.

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Therapeutic Application of Fibrinogen in Spine Surgery: A Review Article

The aim of this review is to investigate current uses of fibrinogen as a tool to reduce operative and postoperative blood loss in different surgical fields especially orthopedic spine surgery.

2021

APRIL

Current and Future Options of Haemophilia A Treatments

The standard treatment of hemophilia A consists of the prophylactic administration of a coagulation factor concentrate, to be administered intravenously several times a week. Newly approved factor concentrates, and non-factor products reduce the frequency of injection and offer better protection against bleeding.

Translating the Success of Prophylaxis in Haemophilia to von Willebrand Disease

There is limited awareness of von Willebrand disease (VWD), leading to challenges in both diagnosis and defining the optimal treatment approach for these patients.

Pharmacokinetic Study of Kovaltry In Thirty-Five Pediatric Patients Aged <12 Years with Severe Hemophilia A

Kovaltry (BAY81-8973) is an unmodified full-length factor VIII (FVIII) concentrate that enhances the pharmacokinetic (PK) profiles as compared to some other standard half-life time FVIII concentrates. However, the PK of Kovaltry in haemophiliac patients aged <12 years has not been reported previously.

Recombinant Factor VIII Fc for the Treatment of Haemophilia A

Prophylaxis with factor VIII (FVIII) is the current therapeutic approach for people with haemophilia A. However, standard half-life (SHL) FVIII products must be injected frequently, imposing a substantial burden on the individual and making it difficult to tailor therapy according to patient need and lifestyle, which could impact adherence.

Guillain-Barre Syndrome in a Child with COVID-19 Infection

Guillain-Barré syndrome (GBS) is characterized by a monophasic, ascending, and symmetrical paralysis with areflexia that progresses over days to weeks. It is typically a postinfectious autoimmune process that leads to destruction of myelin.

Immunoglobulin for Myasthenia Gravis

This is a protocol for a Cochrane Review (intervention).

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Efficacy, Safety, and Strategies for Recombinant-Activated Factor VII in Cardiac Surgical Bleeding: A Narrative Review.

As perioperative bleeding continues to be a major source of morbidity and mortality in cardiac surgery, the search continues for an ideal hemostatic agent for use in this patient population.

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Albumin in Advanced Liver Diseases: The Good and Bad of a Drug!

Human serum albumin (HSA) is the most abundant plasma protein, and it regulates diverse body functions. In advanced and decompensated cirrhosis patients, serum albumin levels are low due to reduction in hepatocyte mass and loss due to disease per se and multiple therapeutic interventions.

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A Randomized Trial of Albumin Infusions in Hospitalized Patients with Cirrhosis

Infection and increased systemic inflammation cause organ dysfunction and death in patients with decompensated cirrhosis. Preclinical studies provide support for an anti-inflammatory role of albumin, but confirmatory large-scale clinical trials are lacking.

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Fundamental Knowledge About the Physical and Chemical Properties of Commercial Albumin and Its Application in Clinical Practice.

Human albumin (HA) or serum albumin is encoded by the ALB gene and is the most abundant plasma protein in mammals. HA is essential for maintaining the osmotic pressure needed for proper distribution of body fluids between intravascular compartments and body tissues.

2021

MAART

Management of COVID‐19‐associated coagulopathy in persons with haemophilia

The SARS-CoV-2 coronavirus-induced infection (COVID-19) can be associated with a coagulopathy mainly responsible for pulmonary microvasculature thrombosis and systemic thromboembolic manifestations.

Immune Responses to Plasma-Derived Versus Recombinant FVIII Products

The most severe side effect of hemophilia treatment is the inhibitor development occurring in 30% of patients, during the earliest stages of treatment with factor (F)VIII concentrates. These catastrophic immune responses rapidly inactivate the infused FVIII, rendering the treatment ineffective. This complication is associated with a substantial morbidity and mortality.

Novel treatments for hemophilia through rebalancing of the coagulation cascade

Hemophilia A and B are inherited hemorrhagic disorders that result from alterations in the coagulation cascade. Aside from spontaneous bleeding, the main complication of hemophilia is hemarthrosis.

Activated factor VIII-mimicking effect by emicizumab on thrombus formation in type 2N von Willebrand disease under high shear flow conditions

Type 2N von Willebrand disease (2NVWD) is characterized by a mild to moderate reduction in plasma levels of factor (F)VIII associated with defective binding of von Willebrand factor (VWF) to FVIII and accelerated proteolysis and clearance of FVIII.

Von Willebrand disease: What does the future hold?

Von Willebrand disease (VWD) is characterized by its heterogeneous clinical manifestation, which complicates its diagnosis and management. The clinical management of VWD has remained essentially unchanged over the last 30 years or so, using von Willebrand factor (VWF) concentrates, desmopressin and anti-fibrinolytic agents as main tools to control bleeding.

Biochemical, molecular, and clinical aspects of coagulation factor VII and its role in hemostasis and thrombosis

Activated factor VII (FVIIa), the first protease of clotting, expresses its physiological procoagulant potential only after complexing with tissue factor (TF) exposed to blood. Deep knowledge of the FVIIa-TF complex and F7 gene helps to understand the Janus-faced clinical findings associated to low or elevated FVII activity (FVIIc).

Role of immunoglobulin and antibodies in disease management

The immune system is a highly advanced and coordinated mechanism that allows a living organism to distinguish between "self" and "non-self". The host uses both innate and adaptive immune response mechanisms to identify and eliminate pathogenic microorganisms.

Efficacy and safety of intravenous immunoglobulins for the treatment of viral encephalitis: a systematic literature review

For most viral encephalitides, therapy is merely supportive. Intravenous immunoglobulins (IVIG) have been used as a prophylactic and therapeutic approach. We conduct a systematic review on the safety and efficacy of IVIG in viral encephalitis.

Characterization of antibodies in human immunoglobulin products from different regions worldwide

AIM: The antibody levels against a broad spectrum of pathogens were assessed in commercial intravenous immunoglobulin (IVIG) manufactured from pooled plasma obtained from different global regions.

Effects of adjunct treatment with intravenous immunoglobulins on the course of severe COVID-19: results from a retrospective cohort study

OBJECTIVES: To evaluate the effect of adjunct treatment with Octagam, an intravenous immunoglobulin (IVIG) product, on clinical outcomes and biomarkers in critically ill COVID-19 patients.

Review of indications for immunoglobulin (IG) use: Narrowing the gap between supply and demand

Cellular blood components and plasma-derived medicinal products (PDMPs) are obtained from blood donated by volunteers. In a growing number of countries, in line with World Health Organization advice issued since the mid-1970s, donors are not remunerated. In recent decades, considerable efforts have been made to restrict the indications for labile blood components to those based on evidence, to ensure efficacy and safety.

Real life picture of the use of intravenous immunoglobulins in idiopathic inflammatory myopathies: Results of a multicentric study

BACKGROUND: despite the absence of specific guidelines, the treatment with intravenous immunoglobulins (IvIg) is considered effective in patients with refractory idiopathic inflammatory myopathies (IIM). The aim of our study is to evaluate the effectiveness and the safety of IvIg and define the possible profile of IIM patients candidate to IvIg treatment.

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Role of fibrinogen concentrates for treatment of critical perioperative hemorrhage

Acquired hypofibrinogenemia is a frequent cause of maintained bleeding in perioperative high-risk settings. Loss, consumption, and dilution under resuscitation fluid therapy are the principal causes for fibrinogen depletion.

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Early and Systematic Administration of Fibrinogen Concentrate in Postpartum Haemorrhage Following Vaginal Delivery: The FIDEL Randomized Controlled Trial

OBJECTIVE: To assess the benefits and safety of early human fibrinogen concentrate in postpartum haemorrhage (PPH) management.

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Association between intraoperative rotational thromboelastometry or conventional coagulation tests and bleeding in liver transplantation: an observational exploratory study

Liver transplantation is associated with major blood loss and transfusions. Our objective was to evaluate the association between coagulation results (rotational thromboelastometry (ROTEM) and conventional coagulation tests) and intraoperative bleeding or perioperative red blood cell (RBC) transfusions in liver transplantation.

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Thrombin Generation Following Severe Trauma: Mechanisms, Modulators, and Implications for Hemostasis and Thrombosis

Thrombin is the central coagulation enzyme that catalyzes the conversion of fibrinogen to form insoluble fibrin blood clots. In vivo, thrombin production results from the concerted effort of plasma enzymatic reactions with essential contributions from circulating and vessel wall cells.

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Transfusion with Cryoprecipitate for Very Low Fibrinogen Levels Does Not Affect Bleeding or Survival in Critically Ill Cirrhosis Patients

Fibrinogen (FIB) levels less than 150 mg/dL have been associated with increased rates of bleeding and lower survival in critically ill cirrhosis patients.

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Thrombotic Thrombocytopenic Purpura: Pathophysiology, Diagnosis, and Management

Thrombotic thrombocytopenic purpura (TTP) is a rare thrombotic microangiopathy characterized by microangiopathic hemolytic anemia, severe thrombocytopenia, and ischemic end organ injury due to microvascular platelet-rich thrombi. TTP results from a severe deficiency of the specific von Willebrand factor (VWF)-cleaving protease, ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13).

2021

FEBRUARI

Von Willebrand disease type 2N: an update

Quantitative or qualitative defects of von Willebrand factor (VWF) are responsible for the most common inherited bleeding disorder, von Willebrand disease (VWD).

The availability of new drugs for hemophilia treatment

A number of new FVIII/IX concentrates enriched the portfolio of products available for the treatment of hemophilia A/B patients.

Incidence of von Willebrand disease in Denmark, 1995-2016: A cohort study

Information about temporal development of von Willebrand disease (VWD) incidence at a population level is scarce. To our knowledge, no study has described the incidence of VWD at a population level.

Efficacy and safety of a recombinant Von Willebrand Factor treatment in patients with inherited Von Willebrand Disease requiring surgical procedures

Von Willebrand Disease is a common inherited haemorrhagic disorder due to a deficiency of Von Willebrand Factor (VWF). In case of surgical procedures in patients who are not responsive or have contraindications to desmopressin, replacement therapy with VWF concentrates is indicated.

Key questions in the new hemophilia era: update on concomitant use of FVIII and emicizumab in hemophilia A patients with inhibitors

Immune tolerance induction (ITI) is the primary therapeutic strategy and only proven method to eradicate inhibitors to coagulation factor VIII (FVIII) in hemophilia A. Emicizumab, a humanized bispecific monoclonal antibody that mimics the function of activated FVIII, has expanded options to treat hemophilia A.

Phase II Open Label Study of Anakinra in Intravenous Immunoglobulin-Resistant Kawasaki Disease

Anakinra has been shown to be successful in preventing and treating cardiovascular lesions both in experimental murine models of Kawasaki disease (KD) and in several studies on intravenous immunoglobulin (IVIG)- and steroid-resistant patients with KD.

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Transfusion with Cryoprecipitate for Very Low Fibrinogen Levels Does Not Affect Bleeding or Survival in Critically Ill Cirrhosis Patients

Fibrinogen (FIB) levels less than 150 mg/dL have been associated with increased rates of bleeding and lower survival in critically ill cirrhosis patients.

2021

JANUARI

ADAMTS13 activity, high VWF and FVIII levels in the pathogenesis of deep vein thrombosis

Deep vein thrombosis (DVT) is a common multi-factorial disease with a partially understood aetiology. Although the roles of high factor (F)VIII and von Willebrand factor (VWF) levels are recognized, that of ADAMTS13 is still unclear.

Real-world evidence on Kovaltry (81-8973) in children with moderate or severe hemophilia A in Europe: a nested cohort analysis

Untreated hemophilia A patients may experience recurrent bleeding events leading to debilitating joint damages.

Long-term outcomes with emicizumab prophylaxis for hemophilia A with/without FVIII inhibitors from the HAVEN 1-4 studies

Prophylaxis with emicizumab-a subcutaneously administered, bispecific, humanized, monoclonal antibody-promotes effective hemostasis in persons with hemophilia A (PwHA).

Rise of levels of von Willebrand factor and factor VIII with age: Role of genetic and acquired risk factors

Von Willebrand factor (VWF) levels are regulated by genetic and acquired factors. The acquired factors are mostly related to age and could be mediators of the age effect on VWF levels.

Implications of a Change of Paradigm in Alpha1 Antitrypsin Deficiency Augmentation Therapy: from Biochemical to Clinical Efficacy

Ever since the first studies, restoring proteinase imbalance in the lung has traditionally been considered as the main goal of alpha1 antitrypsin (AAT) replacement therapy.

Antibodies to watch in 2021

In this 12th annual installment of the Antibodies to Watch article series, we discuss key events in antibody therapeutics development that occurred in 2020 and forecast events that might occur in 2021.

Efficacy and safety of antiviral prophylaxis during pregnancy to prevent mother-to-child transmission of hepatitis B virus: a systematic review and meta-analysis

To eliminate mother-to-child transmission (MTCT) of hepatitis B virus (HBV), peripartum antiviral prophylaxis might be required for pregnant women infected with HBV who have a high risk of MTCT despite infant immunoprophylaxis.

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Exploratory in vitro evaluation of thrombin generation of eptacog beta (recombinant human fviia) and emicizumab in congenital haemophilia A plasma

Introduction/Aim Eptacog beta is a recombinant activated human factor VII approved to treat and control bleeding in haemophilia A and B patients with inhibitors.

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Clinical phenotype, fibrinogen supplementation and health-related quality of life in patients with afibrinogenemia

Due to its low prevalence, epidemiologic data on afibrinogenemia are limited and none are available on health-related quality of life (HRQoL).

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Pharmacokinetics, surrogate efficacy, and safety evaluations of a new human plasma-derived fibrinogen concentrate (FIB Grifols) in adult patients with congenital afibrinogenemia

Congenital afibrinogenemia is a rare coagulation disorder resulting from a deficiency in fibrinogen. This study assessed the pharmacokinetics, surrogate efficacy, and safety of FIB Grifols, a new human plasma-derived fibrinogen concentrate, to treat congenital afibrinogenemia.

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Variations and obstacles in the use of coagulation factor concentrates for major trauma bleeding across Europe: outcomes from a European expert meeting

Trauma is a leading cause of mortality, with major bleeding and trauma-induced coagulopathy (TIC) contributing to negative patient outcomes.

ASH ISTH NHF WFH 2021 guidelines on the management of von Willebrand disease

von Willebrand disease (VWD) is a common inherited bleeding disorder. Significant variability exists in management options offered to patients.

Alpha-1 Antitrypsin for COVID-19 Treatment: Dual Role in Antiviral Infection and Anti-Inflammation

Many drugs have been approved for clinical trials for the treatment of COVID-19 disease, focusing on either antiviral or anti-inflammatory approaches. Combining antiviral and anti-inflammatory drugs or therapies together may be more effective.

State of the art of genetic studies in hemophilia carriers

The new molecular tools and, remarkably the next-generation sequencing (NGS), have driven not only rapid and confident genetic counseling and prenatal diagnosis in hemophilia but also advanced reproductive alternatives, such as preimplantation and noninvasive prenatal diagnoses.

General concepts on hemophilia A and on women carrying the disease

Hemophilia A affects one in every 5000 live male births.

Management of Elective Procedures in Low von Willebrand factor patients in the LoVIC study

Most individuals with mild to moderate reductions in plasma VWF levels do not demonstrate increased bleeding. However, some patients with plasma VWF levels in the 30-50 IU/dL do have a significant bleeding phenotype.

Monocytes and Macrophages in Alpha-I Antitrypsin Deficiency

Alpha-1 antitrypsin deficiency (AATD) is a genetic condition characterised by low circulating levels of alpha-1 antitrypsin (AAT), a serine proteinase inhibitor.

The potential role of emicizumab prophylaxis in severe von Willebrand disease

Severe von Willebrand disease (VWD) may be associated with chronic joint damage and may require prophylactic therapy. Emicizumab is a humanized bispecific antibody, which mimics the function of coagulation factor VIII (FVIII), and it has been approved for prophylaxis in hemophilia A.

Efficacy and safety of IqYmune (R) in patients with CIDP: PRISM-study results

Meeting abstract, 2020 Peripheral Nerve Society Virtual Event 2020

Evaluating the effects of Intravenous Immunoglobulin (IVIg) on the management of severe COVID-19 cases: A randomized controlled trial

The newly discovered coronavirus has turned into coronavirus disease 2019 (COVID-19) pandemic and it rages at an unprecedented rate. Considering the findings of previous studies on the use of Intravenous Immunoglobulin (IVIg) for treating severe H1N1 infection and the satisfying results for reducing viral load and mortality, this study aimed to investigate the potential usefulness of IVIg for the management of severe cases.

A systematic literature review of the effects of immunoglobulin replacement therapy on the burden of secondary immunodeficiency diseases associated with hematological malignancies and stem cell transplants

Secondary immunodeficiency diseases (SID) caused by hematological malignancies (HMs), stem cell transplant (SCT), and associated therapies are mainly characterized by the presence of hypogammaglobulinemia or antibody production deficits.

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A Comparison of Prothrombin Complex Concentrate and Recombinant Activated Factor VII for the Management of Bleeding with Cardiac Surgery

Bleeding following cardiac surgery that warrants transfusion of blood products is associated with significant complications, including increased mortality at 1 year following surgery.

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Association between ionised calcium and severity of postpartum haemorrhage: a retrospective cohort study

Postpartum haemorrhage (PPH) is often complicated by impaired coagulation. We aimed to determine whether the level of ionised calcium (Ca (2+)), an essential coagulation co-factor, at diagnosis of PPH is associated with bleeding severity.

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Prevention of postoperative bleeding after complex pediatric cardiac surgery by early administration of fibrinogen, prothrombin complex and platelets: a prospective observational study

The primary aim of this prospective observational study was to evaluate the effect of an institutional approach consisting of early preventive fibrinogen, prothrombin complex and platelets administration on coagulation parameters and postoperative bleeding in children.

2020

NOVEMBER

Cost-effectiveness of emicizumab vs bypassing agents in the prevention of bleeding episodes in haemophilia A patients with anti-FVIII inhibitors in France

The development of an anti-FVIII inhibitor is the most serious complication of haemophilia A occurring in up to 30% of severe haemophilic patients.

A new drug for an old concept: aptamer to von Willebrand factor for prevention of arterial and microvascular thrombosis

Von Willebrand factor (VWF) is a large and complex multimeric glycoprotein essential for initiation of hemostasis after vascular injury.

Comparison of bypassing agents in patients on emicizumab using global hemostasis assays

Emicizumab is a humanized bispecific monoclonal antibody licensed for patients with severe haemophilia A with and without inhibitors.

The German Hemophilia Registry: Growing with Its Tasks

Hemophilia is a rare heredity bleeding disorder that requires treatment for life. While few therapeutic options were available in the past, multiple recent breakthroughs have fundamentally altered and diversified hemophilia therapy, with even more new therapeutic options forthcoming.

Effectiveness of emicizumab in preventing life-threatening bleeding complications in type 3 von Willebrand disease with inhibitors: A paediatric report

Effectiveness of emicizumab in preventing life-threatening bleeding complications in type 3 von Willebrand disease with inhibitors: A paediatric report

Real-world data of immune tolerance induction using recombinant factor VIII Fc fusion protein in patients with severe haemophilia A with inhibitors at high risk for immune tolerance induction failure: A follow-up retrospective analysis

Real-world data of immune tolerance induction using recombinant factor VIII Fc fusion protein in patients with severe haemophilia A with inhibitors at high risk for immune tolerance induction failure: A follow-up retrospective analysis

Rise of levels of von Willebrand factor and factor VIII with age: Role of genetic and acquired risk factors

Von Willebrand factor (VWF) levels are regulated by genetic and acquired factors. The acquired factors are mostly related to age and could be mediators of the age effect on VWF levels.

Von Willebrand factor

Von Willebrand factor

Hypothesis: Alpha-1-antitrypsin is a promising treatment option for COVID-19

No definitive treatment for COVID-19 exists although promising results have been reported with remdesivir and glucocorticoids.

Rurioctocog alfa pegol PK-guided prophylaxis in hemophilia A: Results from the phase 3 PROPEL study

Rurioctocog alfa pegol prophylaxis targeting factor VIII (FVIII) troughs 1% is efficacious and well-tolerated in people with hemophilia A (PwHA).

Type I interferon antagonists in clinical development for lupus

Systemic lupus erythematosus (SLE) is a severe chronic and incurable autoimmune disease. Treatment includes glucocorticoids and immunosuppressants which typically result in partial responses, and hence there is a great need for new therapies.

A Randomized Trial of Convalescent Plasma in Covid-19 Severe Pneumonia

Convalescent plasma is frequently administered to patients with Covid-19 and has been reported, largely based on observational data, to improve clinical outcomes. Minimal data are available from adequately powered randomized, controlled trials.

Durability of Responses after SARS-CoV-2 mRNA-1273 Vaccination

We recently reported the results of a phase 1 trial of a messenger RNA vaccine, mRNA-1273, to prevent infection with SARSCoV-2; those interim results covered a period of 57 days after the first vaccination.

Intravenous immunoglobulin immunotherapy for coronavirus disease-19 (COVID-19)

Intravenous immunoglobulin (IVIG), a pooled normal IgG from several thousand healthy donors and one of the commonly used immunotherapeutic molecules for the management of autoimmune and inflammatory diseases, has been explored for the treatment of coronavirus disease-19 (COVID-19).

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Individualized, Intraoperative Dosing of Fibrinogen Concentrate for the Prevention of Bleeding in Neonatal and Infant Cardiac Surgery Using Cardiopulmonary Bypass (FIBCON): A Phase 1b/2a Randomized Controlled Trial

Mediastinal bleeding is common following pediatric cardiopulmonary bypass surgery for congenital heart disease. Fibrinogen concentrate (FC) represents a potential therapy for preventing bleeding.

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Stability of Reconstituted Fibrinogen Concentrate in Hemostatic Function and Concentration

Canadian Armed Forces adopted fibrinogen concentrate (RiaSTAP) for hemostatic resuscitation in the far-forward combat setting, given its potential benefits of reducing blood loss, blood transfusion and mortality, and its long storage stability and high portability.

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Antithrombin Deficiency in Trauma and Surgical Critical Care

Antithrombin deficiency (ATD) was described in 1965 by Olav Egeberg as the first known inherited form of thrombophilia. Today, it is understood that ATDs can be congenital or acquired, leading to qualitative, quantitative, or mixed abnormalities in antithrombin (AT).

A Case Report on an Extremely Rare Disease: Factor XI Deficiency

Factor XI deficiency is a rare condition with an estimated prevalence of about one in one million and is more commonly seen in Ashkenazi Jews (8-9%) due to consanguinity.

Global immunoglobulin supply: steaming towards the iceberg?

This review describes how plasma is sourced for fractionation into plasma-derived medicinal products (PDMPs), such as immunoglobulin (Ig) together with differences between plasma from whole blood (recovered plasma) and from plasmapheresis (source plasma) in terms of global plasma supply.

Refractory CIDP: Clinical characteristics, antibodies, and response to alternative treatment

Objective: To review the clinical characteristics, antibodies, and response to alternative treatments in a cohort of patients with refractory CIDP.

Severe Locked-In-Like Guillain-Barré's Syndrome: Dilemmas in Diagnosis and Treatment

Guillain-Barré's syndrome in childhood can follow an atypical course, increasing the challenges in diagnosis and decisions regarding immunomodulatory treatment. Here, we report the case of on a 13-year-old boy with acute onset Guillain-Barré's syndrome progressing over 40 days to a very severe, locked-in-like syndrome despite intensive immunomodulatory treatment.

COVID-19 and multisystem inflammatory syndrome in children and adolescents

As severe acute respiratory syndrome coronavirus 2 continues to spread worldwide, there have been increasing reports from Europe, North America, Asia, and Latin America describing children and adolescents with COVID-19-associated multisystem inflammatory conditions.

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Efficacy of prehospital administration of fibrinogen concentrate in trauma patients bleeding or presumed to bleed (FIinTIC): A multicentre, double-blind, placebo-controlled, randomised pilot study

The aim of the study was to administer fibrinogen concentrate in the prehospital setting to improve blood clot stability in trauma patients bleeding or presumed to bleed.

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Role of von Willebrand Factor after Injury: It may do More than we Think

Acute traumatic coagulopathy is a complex phenomenon following injury and a main contributor to hemorrhage. It remains a leading cause of preventable death in trauma patients.

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First open label study to investigate the use, safety, and tolerability of octaplaslg® in patient blood management in two cardiac surgery centres in France

Fresh Frozen Plasma (FFP) is used to correct haemostatic function after cardiac surgery with cardio-pulmonary bypass (CPB). As a blood product, availability of FFP can be challenging.

2020

OKTOBER

Pharmacokinetics and Pharmacodynamics of Emicizumab in Persons with Hemophilia A with Factor VIII Inhibitors: HAVEN 1 Study

Emicizumab, a bispecific monoclonal antibody, bridges activated factor IX (FIXa) and FX, replacing the function of missing FVIIIa to restore effective hemostasis in persons with hemophilia A (PwHA). Here we assess pharmacokinetic (PK) and pharmacodynamic (PD) biomarkers in PwHA with FVIII inhibitors in the Phase III HAVEN 1 study (NCT02622321).

New insights into IVIg mechanisms and alternatives in autoimmune and inflammatory diseases

Purpose of review Intravenous immunoglobulin (IVIg) is an effective treatment for an increasing number of autoimmune and inflammatory conditions. However, IVIg continues to be limited by problems of potential shortages and cost.

Dose of intravenous immunoglobulins in chronic inflammatory demyelinating polyneuropathy

The usual initiating dose of intravenous immunoglobulins (IVIg) in the treatment
of chronic inflammatory demyelinating polyneuropathy (CIDP) is 2 g/kg/course. Although not evidence based, subsequent reductions are advised to the lowest possible level for maintenance.

A proposed dosing algorithm for the individualized dosing of human immunoglobulin in chronic inflammatory neuropathies

Dosing guidelines for immunoglobulin (Ig) treatment in neurological disorders do not consider variations in Ig half-life or between patients. Individualization of therapy could optimize clinical outcomes and help control costs.

Clinical and economic comparison of an individualized immunoglobulin protocol vs. standard dosing for chronic inflammatory demyelinating polyneuropathy

The clinical and economic implications of an individualised intravenous immunoglobulin (IVIg) protocol for chronic inflammatory demyelinating polyneuropathy (CIDP) are unknown. Comparison with standard dosing regimens has not been performed

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Efficacy of prehospital administration of fibrinogen concentrate in trauma patients bleeding or presumed to bleed (FIinTIC): A multicentre, double-blind, placebo-controlled, randomised pilot study

The aim of the study was to administer fibrinogen concentrate in the prehospital setting to improve blood clot stability in trauma patients bleeding or presumed to bleed.

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A Randomized Controlled Trial of Antithrombin Supplementation During Extracorporeal Membrane Oxygenation

Supplementation of antithrombin might decrease the amount of heparin needed to achieve a given anticoagulation target during extracorporeal membrane oxygenation. However, exogenous antithrombin itself may increase the risk of bleeding.

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Cryoprecipitate transfusion in bleeding patients

The management of acquired coagulopathy in multiple clinical settings frequently involves fibrinogen supplementation. Cryoprecipitate, a multidonor product, is widely used for the treatment of acquired hypofibrinogenemia following massive bleeding, but it has been associated with adverse events.

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Hemostatic Management of Extracorporeal Circuits Including Cardiopulmonary Bypass and Extracorporeal Membrane Oxygenation

Cardiopulmonary bypass and extracorporeal membrane oxygenation (ECMO) cause hemostatic derangements that can predispose patients to both bleeding and thrombotic complications.

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From Routine to Research Laboratory: Strategies for the Diagnosis of Congenital Fibrinogen Disorders

Congenital fibrinogen disorders (CFDs) encompass a heterogeneous group of fibrinogen defects with a wide spectrum of biological and clinical features. An accurate diagnosis is thus essential to assure the optimal management for the patient.

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Diagnostic accuracy of viscoelastic point-of-care identification of hypofibrinogenaemia in cardiac surgical patients: A systematic review

Hypofibrinogenaemia during cardiac surgery may increase blood loss and bleeding complications. Viscoelastic point-of-care tests provide more rapid diagnosis than laboratory measurement, allowing earlier treatment.

2020

SEPTEMBER

Kreuth V initiative: European consensus proposals for treatment of hemophilia using standard products, extended half-life coagulation factor concentrates and non-replacement therapies

This report contains the updated consensus recommendations for optimal hemophilia care produced in 2019 by three Working Groups (WG) on behalf of the European Directorate for Quality of Medicines and Healthcare in the frame of the Kreuth V Initiative.

‘Haemophilia Guidelines for All': A new ambition of the World Federation of Haemophilia (WFH)

“Treatment for all” is the vision statement of the World Federation of Haemophilia (WFH) which works to improve and sustain care for people with inherited bleeding disorders around the World.

Use of recombinant activated factor VII for uncontrolled bleeding in a haematology/oncology paediatric ICU cohort

Bleeding among critically ill paediatric haematology/oncology (CIPHO) patients leads to significant morbidity and mortality. Recombinant activated factor VII (rFVIIa) has shown some benefits in previous reported off-label use when conventional therapies have failed.

Bleeding complications during pregnancy and delivery in haemophilia carriers and their neonates in Western France: An observational study

Pregnancy, delivery and the postpartum period expose haemophilia carriers, as well as their potentially affected neonates to a high risk of haemorrhagic complications.

Management of previously untreated patients with severe haemophilia A preferentially treated with recombinant factor VIII products: Two French centres' real-life experience

Severe haemophilia A, defined by Factor VIII activity levels < 1 IU/dL, requires prophylactic supplementation.

When should we consider that CIDP patient is non-responder to IVIg?

For CIDP, IVIg treatment is often the first choice as improvement can be fast. However, there is no consensus on when considering alternative therapy (corticosteroids or plasma exchange) for non-responder patients.

Open Label, Phase II Study with Anakinra in Intravenous Immunoglobulin-Resistant Kawasaki Disease

OBJECTIVE: Determine the safety of blocking interleukin 1 in patients with KD that are unresponsive to IVIG.

Diagnosis and treatment of Guillain-Barré Syndrome in childhood and adolescence: An evidence- and consensus-based guideline

This evidence- and consensus-based practical guideline for the diagnosis and treatment of Guillain-Barré Syndrome (GBS) in childhood and adolescence has been developed by a group of delegates from relevant specialist societies and organisations; it is the result of an initiative by the German-Speaking Society of Neuropediatrics (GNP), and is supported by the Association of Scientific Medical Societies (AWMF, Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften).

Randomised trial of intravenous immunoglobulin maintenance treatment regimens in chronic inflammatory demyelinating polradiculoneuropathy

High peak serum IgG levels may not be needed for maintenance treatment of Intravenous immunoglobulin (IVIg) in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and cause side-effects. More frequent lower dosing may lead to more stable IgG levels and higher trough levels which might improve its efficacy.

New insights into IVIg mechanisms and alternatives in autoimmune and inflammatory diseases

Intravenous immunoglobulin (IVIg) is an effective treatment for an increasing number of autoimmune and inflammatory conditions. However, IVIg continues to be limited by problems of potential shortages and cost.

Guillain-Barré syndrome spectrum associated with COVID-19: an up-to-date systematic review of 73 cases

Since coronavirus disease-2019 (COVID-19) outbreak in January 2020, several pieces of evidence suggested an association between the spectrum of Guillain-Barré syndrome (GBS) and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2).

A SARS-CoV-2 vaccine candidate would likely match all currently circulating variants

The magnitude of the COVID-19 pandemic underscores the urgency for a safe and effective vaccine. Many vaccine candidates focus on the Spike protein, as it is targeted by neutralizing antibodies and plays a key role in viral entry.

COVID-19 herd immunity: where are we?

Herd immunity is a key concept for epidemic control.

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COVID-19: Coagulopathy, Risk of Thrombosis, and the Rationale for Anticoagulation

The novel coronavirus infection (COVID-19) is caused by the new coronavirus SARS-CoV-2 and is characterized by an exaggerated inflammatory response that can lead to severe manifestations such as adult respiratory syndrome, sepsis, coagulopathy, and death in a proportion of patients.

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The debate ROTEMs on - the utility of point-of-care testing and fibrinogen concentrate in postpartum haemorrhage

In 2019, McNamara et al. reported 4 years of observational data of their experience of rotational thromboelastometry (ROTEM®, Instrumentation Laboratory, Bedford, MA, USA) in a large UK tertiary obstetrics unit to aid the management of major obstetric haemorrhage.

2020

JUNI

Hemophilia : a disease on the move

Over the last hundred years, the treatment of hemophilia has evolved considerably. To date, its principle is still to prevent the occurrence of hemorrhages by regular intravenous injections of factor VIII or IX concentrate.

Concomitant Use of rFVIIa and Emicizumab in People with Hemophilia A with Inhibitors: Current Perspectives and Emerging Clinical Evidence

Emicizumab, a humanized, bi-specific, monoclonal antibody subcutaneously administered, mimicking the function of FVIIIa, represents a milestone in treatment of patients affected by hemophilia A complicated with inhibitors.

Genetic mosaicism in haemophilia: A practical review to help evaluate the risk of transmitting the disease

Approximately 70% of patients with haemophilia exhibit a clear inheritance pattern, while for the remaining 30%, patients are the first to be diagnosed in their family and are considered sporadic cases.

Annual Bleeding Rates: Pitfalls of Clinical Trial Outcomes in Hemophilia Patients

Emerging treatment options for hemophilia, including gene therapy, modified factor products, antibody-based products, and other nonreplacement therapies, are in development or on their way to marketing authorization.

Six molecular patterns leading to hemophilia A phenotype in 18 females from Poland

Female hemophilia is an intriguing rare disorder and few larger reports on its genetic etiology are available.

Invasive procedures in patients with haemophilia: Review of low-dose protocols and experience with extended half-life FVIII and FIX concentrates and non-replacement therapies

The performance of surgery and invasive procedures in patients with haemophilia is currently facing new challenges globally.

Clinical management of woman with bleeding disorders: A survey among European haemophilia treatment centres

The impact of bleeding for women with bleeding disorders (WBD) is of increasing focus and importance. Despite this, optimal management strategies are unclear and knowledge gaps persist.

Cytokine storm in COVID-19: pathogenesis and overview of anti-inflammatory agents used in treatment.

COVID-19 infection has a heterogenous disease course; it may be asymptomatic or causes only mild symptoms in the majority of the cases, while immunologic complications such as macrophage activation syndrome also known as secondary hemophagocytic lymphohistiocytosis, resulting in cytokine storm syndrome and acute respiratory distress syndrome, may also occur in some patients.

Kawasaki disease: pathophysiology and insights from mouse models

Kawasaki disease is an acute febrile illness and systemic vasculitis of unknown aetiology that predominantly afflicts young children, causes coronary artery aneurysms and can result in long-term cardiovascular sequelae.

A Systematic Review and Meta-regression Analysis on the Impact of Increasing IgG Trough Level on Infection Rates in Primary Immunodeficiency Patients on Intravenous IgG Therapy

We conducted a systematic review and meta-regression analysis to evaluate the impact of increasing immunoglobulin G (IgG) trough levels on the clinical outcomes in patients with PID receiving intravenous immunoglobulin G (IVIG) treatment.

Relationship between post-IVIG IgG levels and clinical outcomes in Kawasaki disease patients: new insight into the mechanism of action of IVIG

The dosing of intravenous immunoglobulin (IVIG) therapy for Kawasaki disease (KD) has been a matter of debate for decades, with recent studies implicating that larger doses lead to better outcomes.

Compendium answering 150 questions on COVID-19 and SARS-CoV-2

In December 2019, China reported the first cases of the coronavirus disease 2019 (COVID-19). This disease, caused by the severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2), has developed into a pandemic.

Delayed specific IgM antibody responses observed among COVID-19 patients with severe progression

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread rapidly worldwide since it was confirmed as the causative agent of COVID-19. Molecular diagnosis of the disease is typically performed via nucleic acid-based detection of the virus from swabs, sputum or bronchoalveolar lavage fluid (BALF).

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A prospective observational study of acute traumatic coagulopathy in traumatic bleeding from the battlefield

Acute trauma coagulopathy (ATC) after military trauma has not been comprehensively studied. ATC is defined as a prolonged prothrombin time ratio (PTr) or reduced clot amplitude (A5) in viscoelastic testing.

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Empirical transfusion strategies for major hemorrhage in trauma patients: A systematic review

Major hemorrhage is a significant cause of mortality and morbidity around the world. There is currently no consensus on the best empirical transfusion strategy.

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A prospective, single-blind, randomized, phase III study to evaluate the safety and efficacy of Fibrin Sealant Grifols as an adjunct to hemostasis compared with manual compression in vascular surgery

New formulations and applications of hemostatic adjuncts such as fibrin sealant (FS) to support local hemostasis and sutures continue to be developed.

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Current perspective on fibrinogen concentrate in critical bleeding

Massive hemorrhage continues to be a treatable cause of death. Its management varies from prefixed ratio-driven administration of blood components to goal-directed therapy based on point-of-care testing and administration of coagulation factor concentrates.

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Anticoagulant treatment and bleeding complications in patients with left ventricular assist devices

The treatment options for advanced heart failure patients drastically changed with the introduction of left ventricular assist devices (LVADs), either as bridge to transplant or as destination therapy for patients ineligible for transplant.

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Which is the preferred blood product for fibrinogen replacement in the bleeding patient with acquired hypofibrinogenemia-cryoprecipitate or fibrinogen concentrate?

The importance of the targeted treatment of acquired hypofibrinogenemia during hemorrhage with a concentrated fibrinogen product (either cryoprecipitate or fibrinogen concentrate) cannot be underestimated.

von Willebrand Factor and Factor VIII Clearance in Perioperative Hemophilia A Patients

von Willebrand factor (VWF) is crucial for optimal dosing of factor VIII (FVIII) concentrate in hemophilia A patients as it protects FVIII from premature clearance. To date, it is unknown how VWF behaves and what its impact is on FVIII clearance in the perioperative setting.

Antithrombotic and hemostatic stewardship: evaluation of clinical outcomes and adverse events of recombinant factor VIIa (Novoseven®) utilization at a large academic medical center

Recombinant factor VIIa (rFVIIa) (Novoseven) is utilized for the reversal of anticoagulation-associated bleeding and refractory bleeding in cardiac surgery.

Concomitant Use of rFVIIa and Emicizumab in People with Hemophilia A with Inhibitors: Current Perspectives and Emerging Clinical Evidence

Emicizumab, a humanized, bi-specific, monoclonal antibody subcutaneously administered, mimicking the function of FVIIIa, represents a milestone in treatment of patients affected by hemophilia A complicated with inhibitors.

von Willebrand disease: Diagnosis and treatment, treatment of women, and genomic approach to diagnosis

von Willebrand disease (VWD) is the most common inherited bleeding disorder. VWD is caused by deficiencies in von Willebrand factor (VWF), a critical adhesive haemostatic protein. This review provides an overview of VWD diagnosis and treatment, special considerations in treating women with VWD, and current genomic approaches to VWD.

The acquired von Willebrand syndrome focused for hematologists

The acquired von Willebrand syndrome (AVWS) is a rare bleeding disorder with laboratory findings similar to those of inherited von Willebrand disease.

Factor VIII binding affects the mechanical unraveling of the A2 domain of von Willebrand factor

Proteolytic cleavage of von Willebrand factor (VWF) by ADAMTS13 is crucial for normal hemostasis.

Management of thrombosis in a pediatric renal transplant patient with factor VII deficiency A dilemma concerning recombinant factor VIIa

Hemorrhagic complications in surgical patients with congenital factor VII deficiency are a major concern.

Confronting COVID-19: Issues in Hemophilia and Congenital Bleeding Disorders

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), emerging toward the end of 2019 in an epidemic focused in Wuhan, China, is responsible for Coronavirus Disease 2019 (COVID-19).

Recovery of severely ill COVID-19 patients by intravenous immunoglobulin (IVIG) treatment: A case series

During the recent months, COVID-19 has turned to a global crisis claiming high mortality and morbidity among populations. Despite the high prevalence of the disease, it has currently no definitive treatment.

A promising antiviral candidate drug for the COVID-19 pandemic: A mini-review of remdesivir

Remdesivir (GS-5734), a viral RNA-dependent RNA polymerase (RdRP) inhibitor that can be used to treat a variety of RNA virus infections, is expected to be an effective treatment for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

Autoinflammatory and autoimmune conditions at the crossroad of COVID-19

Coronavirus disease 2019 (COVID-19) has been categorized as evolving in overlapping phases.

COVID-19 convalescent plasma: phase 2

As transfusion medicine specialists we understood the potential that convalescent plasma (CCP) could play early in the management of patients with COVID-19.

Practical guidance for the management of adults with immune thrombocytopenia during the COVID-19 pandemic

This document aims to provide practical guidance for the assessment and management of patients with thrombocytopenia, with a particular focus on immune thrombocytopenia (ITP), during the COVID-19 pandemic.

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Albumin in decompensated cirrhosis: new concepts and perspectives

The pathophysiological background of decompensated cirrhosis is characterised by a systemic proinflammatory and pro-oxidant milieu that plays a major role in the development of multiorgan dysfunction.

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Coagulopathy in COVID-19

The COVID-19 pandemic has become an urgent issue in every country. Based on recent reports, the most severely ill patients present with coagulopathy, and disseminated intravascular coagulation (DIC)-like massive intravascular clot formation is frequently seen in this cohort.

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Standardizing Care to Manage Bleeding Disorders in Adolescents with Heavy Menses-A Joint Project from the ISTH Pediatric/Neonatal and Women's Health SSCs

Bleeding disorders (BD) are under-recognized in adolescents with heavy menstrual bleeding (HMB).

2020

MEI

Management of von Willebrand disease with a factor VIII-poor von Willebrand factor concentrate: results from a prospective observational post-marketing study

A triple-secured plasma-derived von Willebrand factor (pdVWF) almost devoid of FVIII (WILFACTIN®) was approved in France in 2003, and then in other countries for the treatment of patients with von Willebrand disease (VWD).

New developments in von Willebrand disease

Von Willebrand disease (VWD) constitutes the most common inherited human bleeding disorder. It is associated with a mucocutaneous bleeding phenotype that can significantly impact upon quality of life.

Traumatic injury results in prolonged circulation of ultralarge von Willebrand factor and a reduction in ADAMTS13 activity

Increases in plasma von Willebrand Factor (VWF) levels, accompanied by decreases in the metalloprotease ADAMTS13, have been demonstrated soon after traumatic injury while downstream effects remain unclear.

Higher rates of bleeding and use of treatment products among young boys compared to girls with von Willebrand disease

There are limited observational studies among children diagnosed with von Willebrand Disease (VWD). We analyzed differences in bleeding characteristics by sex and type of VWD using the largest reported surveillance database of children with VWD (n = 2712), ages 2 to 12 years old.

Prevalence and Incidence of Non-neutralizing Antibodies in Congenital Hemophilia A- A Systematic Review and Meta-Analysis

In hemophilia A the presence of non-neutralizing antibodies (NNAs) against Factor VIII (FVIII) may predict the development of neutralizing antibodies (inhibitors) and accelerate the clearance of administrated FVIII concentrates.

Long-term safety and efficacy of rituximab in 248 adults with immune thrombocytopenia: Results at 5 years from the French prospective registry ITP-ritux

Rituximab is a second-line option in adults with immune thrombocytopenia (ITP), but the estimated 5-year response rate, only based on pooled retrospective data, is about 20%, and no studies have focused on long-term safety.

Patient experience with subcutaneous immunoglobulin 20%, Ig20Gly, for primary immunodeficiency diseases: a prespecified post hoc analysis of combined data from 2 pivotal trials

Often, patients with primary immunodeficiency diseases (PID), which are marked by the absence or loss of functional antibodies, require lifelong treatment with immunoglobulin (IG) replacement therapy administered either intravenously (intravenous immunoglobulin [IVIG]) or subcutaneously (subcutaneous immunoglobulin [SCIG]).

Response to eculizumab in patients with myasthenia gravis recently treated with chronic IVIg: a subgroup analysis of REGAIN and its open-label extension study

In the phase III eculizumab for refractory generalized myasthenia gravis REGAIN study [ClinicalTrials.gov identifier: NCT01997229] and its open-label extension (OLE) [ClinicalTrials.gov identifier: NCT02301624], patients with treatment-refractory antiacetylcholine receptor antibody-positive generalized myasthenia gravis had clinically meaningful improvements with eculizumab versus placebo.

COVID-19 in patients with myasthenia gravis

Coronavirus disease 2019 (COVID-19) has rapidly become a global pandemic, but little is known about its potential impact on patients with myasthenia gravis (MG).

Immune Thrombocytopenia in Adults: Modern Approaches to Diagnosis and Treatment

Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder affecting approximately 1 in 20,000 people.

Virological assessment of hospitalized patients with COVID-2019

Coronavirus disease 2019 (COVID-19) is an acute infection of the respiratory tract that emerged in late 2019. Initial outbreaks in China involved 13.8% of cases with severe courses, and 6.1% of cases with critical courses.

Comparison of Clinical Characteristics of Patients with Asymptomatic vs Symptomatic Coronavirus Disease 2019 in Wuhan, China

Coronavirus disease 2019 (COVID-19) emerged in Wuhan, China, in December 2019 and has spread globally with sustained human-to-human transmission outside China.

Rational Use of Tocilizumab in the Treatment of Novel Coronavirus Pneumonia

Since December 2019, a novel coronavirus pneumonia (COVID-19) has broken out in Wuhan, China and spread rapidly. Recent studies have found that ̴ 15.7% of patients develop severe pneumonia, and cytokine storm is an important factor leading to rapid disease progression.

Treatment of COVID-19 Patients with Convalescent Plasma

COVID-19 disease, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread globally, and no proven treatments are available.

Impact of immune enhancement on Covid-19 polyclonal hyperimmune globulin therapy and vaccine development

The pandemic spread of a novel coronavirus – SARS coronavirus-2 (SARS-CoV-2) as a cause of acute respiratory illness, named Covid-19, is placing the healthcare systems of many countries under unprecedented stress.

Effect of Convalescent Plasma Therapy on Time to Clinical Improvement in Patients with Severe and Life-threatening COVID-19: A Randomized Clinical Trial

What is the effect of convalescent plasma therapy added to standard treatment, compared with standard treatment alone, on clinical outcomes in patients with severe or life-threatening coronavirus disease 2019 (COVID-19)?

COVID-19 Convalescent Plasma: Now Is the Time for Better Science

In this issue of Transfusion Medicine Reviews, we are pleased to offer readers an assessment as of April 2020 of COVID-19 Convalescent Plasma (CCP) by H. Cliff Sullivan and John Roback of Emory University in Atlanta.

A Randomized Trial of Convalescent Plasma for COVID-19 - Potentially Hopeful Signals

Convalescent plasma for the treatment of infectious diseases has been used since the early 20th century and was associated with reduced mortality during the 1918 influenza, 2003 SARS, and 2009 influenza H1N1 pandemics.

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Efficacy and Safety of Fibrinogen Concentrate for Congenital Fibrinogen Deficiency in Children

Efficacy and Safety of Fibrinogen Concentrate for Congenital Fibrinogen Deficiency in Children.

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Pathophysiological Response to Trauma-Induced Coagulopathy: A Comprehensive Review

Hypercoagulability can occur after severe tissue injury, that is likely related to tissue factor exposure and impaired endothelial release of tissue plasminogen activator (tPA).

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Evolution of viscoelastic coagulation testing

The methods of viscoelastic coagulation testing (VCT) have evolved since the original invention of thrombelastography over 60 years ago, and new generations of devices are clinically used to guide hemostatic interventions at bedside.

Bleeding symptoms in patients diagnosed as type 3 Von Willebrand Disease: results from 3WINTERS-IPS, an international and collaborative cross-sectional study

Type 3 von Willebrand's disease (VWD) patients present markedly reduced levels of von Willebrand factor and factor VIII.

Evolution of replacement therapy for von Willebrand disease: From plasma fraction to recombinant von Willebrand factor

The diagnosis and treatment of von Willebrand disease (VWD) are challenging, in part because patients exhibit a wide range of bleeding patterns and manifestations (e.g. epistaxis, gingival bleeding, heavy menstrual bleeding, gastrointestinal bleeds, postoperative bleeding, hemarthroses) and in part because many tests are required to make an accurate diagnosis.

Guidelines for the prophylaxis of haemophilia A and B: new horizons and ambitions

Guidelines for the prophylaxis of haemophilia A and B: new horizons and ambitions

Differentiation of Patients with Symptomatic Low von Willebrand Factor from Those with Asymptomatic Low von Willebrand Factor

Accurate diagnosis of symptomatic low von Willebrand factor (VWF) remains a major challenge in von Willebrand disease (VWD).

Show me the evidence: Effectiveness of low-dose prophylaxis

Prophylaxis is the gold standard treatment for haemophilia but requires more amount of clotting factor concentrates, than on demand therapy. Low dose prophylaxis is an alternative for countries with limited resources.

Detection of alpha-1 antitrypsin deficiency: the past, present and future

Most patients with alpha-1 antitrypsin deficiency remain undiagnosed and therefore do not benefit from current therapies or become eligible for research studies of new treatments under development.

Alpha-1 Antitrypsin Deficiency: Have We Got the Right Proteinase?

Alpha-1 antitrypsin deficiency (AATD) has traditionally been associated with the development of early onset panlobular emphysema thought to reflect the direct interstitial damage caused by neutrophil elastase.

Origin and nature of the neutralizing immune response against therapeutic factor VIII

The use of therapeutic proteins induces in some patients the appearance of neutralizing antibodies.

Evaluation of coagulation factor activity and sterility of thawed fresh frozen plasma during storage up to 5 days at 4 degrees C

Fresh frozen plasma (FFP) is a blood component containing functional quantities of all coagulation factors stored at -18 degrees C or below. FFP has to be thawed and transfused as soon as possible to prevent the loss of certain coagulation factor activities and to minimise microbial contamination.

Factor VIII activity and bleeding risk during prophylaxis for severe hemophilia A: a population pharmacokinetic model

During factor VIII prophylaxis for severe hemophilia A, bleeding risk increases with time when factor VIII activity is below 1%.

International recommendations on the diagnosis and treatment of acquired hemophilia A

Acquired hemophilia A (AHA), a rare bleeding disorder caused by neutralizing autoantibodies against coagulation factor VIII (FVIII), occurs in both men and women without a previous history of bleeding.

Antibody-mediated complement activation in pathology and protection

Antibody-dependent complement activity is associated not only with autoimmune morbidity, but also with antitumor efficacy.

Effect of intravenous immunoglobulin G therapy on natural killer cell function related to Fc gamma receptor gene expression

Effect of intravenous immunoglobulin G therapy on natural killer cell function related to Fc gamma receptor gene expression

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How we manage haemostasis during sepsis

Sepsis may be associated with activation of the coagulation system and, in its most severe form, may result in disseminated intravascular coagulation (DIC).

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Trials and Tribulations of Viscoelastic-Based Determination of Fibrinogen Concentration

Acquired fibrinogen deficiency is a major determinant of severe bleeding in different clinical conditions, including cardiac surgery, trauma, postpartum hemorrhage, liver surgery, and transplantation.

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More Is Not Always Better: Effects of Cell Salvage in Cardiac Surgery on Postoperative Fibrinogen Concentrations

More Is Not Always Better: Effects of Cell Salvage in Cardiac Surgery on Postoperative Fibrinogen Concentrations

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The gut microbiome and thromboembolism

The gut microbiome plays a critical role in various inflammatory conditions, and its modulation is a potential treatment option for these conditions.

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Comparison of Two Different Fibrinogen Concentrates in an in vitro Model of Dilutional Coagulopathy

Fibrinogen concentrates are widely used to restore clot stability in situations of bleeding. Fibrinogen preparations are produced using different production methods, resulting in different compounds. Thus, different preparations might have a distinct impact on blood coagulation.

2020

APRIL

Escape or Fight: Inhibitors in Hemophilia A

Replacement therapy with coagulation factor VIII (FVIII) represents the current clinical treatment for patients affected by hemophilia A (HA).

Comparative assessment of von Willebrand factor multimers vs activity for von Willebrand disease using modern contemporary methodologies

Diagnosis of von Willebrand disease (VWD) is challenging due to heterogeneity of VWD and test limitations. Many von Willebrand factor (VWF) assays are utilized, including antigen (Ag), activity and multimer analysis.

Recombinant factor VIII Fc fusion protein for the treatment of severe haemophilia A: Final results from the ASPIRE extension study

The efficacy and safety of recombinant factor VIII Fc fusion protein (rFVIIIFc) as an extended half-life treatment for severe haemophilia A were demonstrated in the Phase 3 A-LONG and Kids A-LONG studies.

The Australian experience with switching to extended half-life factor VIII and IX concentrates: On behalf of the Australian Haemophilia Centre Directors' Organization

Extended half-life (EHL) factor (F) VIII and FIX concentrates became available to selected haemophilia A (HA) and haemophilia B (HB) patients in Australia in March 2018.

Hemophilia A and von Willebrand deficiency: therapeutic implications

Hemophilia A is an X-linked bleeding disorder caused by a deficiency of factor VIII.

Product type and the risk of inhibitor development in nonsevere haemophilia A patients: a case-control study

Inhibitor development is a major complication of treatment with factor VIII concentrates in nonsevere haemophilia A.

Hemophilia management: Huge impact of a tiny difference

Hemophilia A and B are inherited X-linked disorders of hemostasis, associated with an increased bleeding tendency.

Efficacy and safety of octanorm (cutaquig(®)) in adults with primary immunodeficiencies with predominant antibody deficiency: a prospective, open-label study

AIM: To evaluate efficacy and safety of octanorm (16.5% subcutaneous immunoglobulin) in adult patients with primary immunodeficiencies.

Preliminary Results of a Randomized Clinical Trial of Intravenous Immunoglobulin in Solid Organ Recipients with Severe Infection and Secondary Antibody Deficiency

Infection is a cause of death in solid organ transplantation. Secondary antibody deficiency is a risk factor of severe infection in solid organ transplantation.

Prophylaxis of Hepatitis B Virus (HBV) Re-Infection in Liver Transplantation: Is the Reappearance of Hepatitis B Surface Antigen (HBsAg) Significant?

The recurrence of hepatitis B virus (HBV) infection after orthotopic liver transplantation (OLT) was in the past a primary cause of organ loss or mortality.

Chloroquine diphosphate in two different dosages as adjunctive therapy of hospitalized patients with severe respiratory syndrome in the context of coronavirus (SARS-CoV-2) infection: Preliminary safety results of a randomized, double-blinded, phase IIb clinical trial (CloroCovid-19 Study)

There is no specific antiviral therapy recommended for the disease caused by SARS-CoV-2 (COVID-19). Recent publications have drawn attention to the possible benefit of chloroquine (CQ).

Neutralizing antibody responses to SARS-CoV-2 in a COVID-19 recovered patient cohort and their implications

The COVID-19 pandemic caused by SARS-CoV-2 coronavirus threatens global public health. Currently, neutralizing antibodies (NAbs) versus this virus are expected to correlate with recovery and protection of this disease.

Structural and Functional Basis of SARS-CoV-2 Entry by Using Human ACE2

The recent emergence of a novel coronavirus (SARS-CoV-2) in China has caused significant public health concerns. Recently, ACE2 was reported as an entry receptor for SARS-CoV-2.

Pharmacologic Treatments for Coronavirus Disease 2019 (COVID-19): A Review

The pandemic of coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents an unprecedented challenge to identify effective drugs for prevention and treatment.

COVID-19: Attacks the 1-Beta Chain of Hemoglobin and Captures the Porphyrin to Inhibit Human Heme Metabolism

The novel coronavirus pneumonia (COVID-19) is an infectious acute respiratory infection caused by the novel coronavirus. The virus is a positive-strand RNA virus with high homology to bat coronavirus.

Safety considerations with chloroquine, hydroxychloroquine and azithromycin in the management of SARS-CoV-2 infection

Severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) has spread rapidly around the globe in recent months.

Effectiveness of convalescent plasma therapy in severe COVID-19 patients

Currently, there are no approved specific antiviral agents for novel coronavirus disease 2019 (COVID-19). In this study, 10 severe patients confirmed by real-time viral RNA test were enrolled prospectively.

Severe Acute Respiratory Syndrome Coronavirus 2 RNA Detected in Blood Donations

Because of high rates of 2019 novel coronavirus disease in Wuhan, China, Wuhan Blood Center began screening for severe acute respiratory syndrome coronavirus 2 RNA on January 25, 2020.

Deployment of convalescent plasma for the prevention and treatment of COVID-19

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease (COVID-19), has spurred a global health crisis.

Coronavirus Disease 2019: Coronaviruses and Blood Safety

With the outbreak of unknown pneumonia in Wuhan, China, in December 2019, a new coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), aroused the attention of the entire world. The current outbreak of infections with SARS-CoV-2 is termed Coronavirus Disease 2019 (COVID-19).

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Comparison of fresh frozen plasma vs. coagulation factor concentrates for reconstitution of blood: An in vitro experimental study

Many trauma centres have adopted the administration of fixed ratios of packed red blood cells (PRBCs), platelet concentrates and fresh frozen plasma (FFP) for bleeding patients. However, the haemostatic efficacy of this concept is not well proven.

A Molecular Revolution in the Treatment of Hemophilia

For decades, the monogenetic bleeding disorders hemophilia A and B (coagulation factor VIII and IX deficiency) have been treated with systemic protein replacement therapy. Now, diverse molecular medicines, ranging from antibody to gene to RNA therapy, are transforming treatment.

Turoctocog alfa pegol provides effective management for major and minor surgical procedures in patients across all age groups with severe haemophilia A: Full data set from the pathfinder 3 and 5 phase III trials

Turoctocog alfa pegol is a glycoPEGylated recombinant factor VIII (FVIII) with an extended half-life developed for prophylaxis, treatment of bleeds and perioperative management in patients with haemophilia A.

Guidance on the diagnosis and management of Platelet- type von Willebrand Disease: a communication from the platelet physiology subcommittee of the ISTH.

Platelet- type von Willebrand Disease (PT-VWD) is a rare autosomal dominant platelet bleeding disorder, with fifty-five patients reported worldwide so far, probably frequently misdiagnosed.

Long-term analysis of the benefit of prophylaxis for adult patients with severe or moderate haemophilia A

Prophylaxis with factor VIII (FVIII) concentrates in children with haemophilia A (HA) is current standard of care. The benefit of prophylactic treatment for adult HA patients is not commonly accepted.

Factor VIII and IX assays for post-infusion monitoring in hemophilia patients: guidelines from the French BIMHO group (GFHT)

Replacement therapy with plasma-derived or recombinant FVIII and FIX (pdFVIII/pdFIX or rFVIII/rFIX) concentrates is the standard of treatment in patients with hemophilia A and B respectively.

Alpha-1 Antitrypsin Deficiency and Pregnancy

Alpha-1 Antitrypsin Deficiency (A1AD) is a hereditary condition characterized by low levels of circulating alpha-antitrypsin (AAT) in plasma.

Advances in managing rare acquired bleeding disorders

Rare acquired bleeding disorders include a wide spectrum of coagulopathies characterized by spontaneous or post-trauma and post-surgery hemorrhages in patients without a previous personal or family history of bleeding.

FVIII/VWF complex displays a greater pro-haemostatic activity than FVIII preparations devoid of VWF: Study in plasma and cell-based models.

Plasma-derived FVIII/VWF complex was reported to be less sensitive to inhibitors than FVIII preparations devoid of VWF.

Real Life Population Pharmacokinetics Modelling of Eight Factors VIII in Patients with Severe Haemophilia A: Is It Always Relevant to Switch to an Extended Half-Life?

We retrospectively analysed the data files of 171 adults and 87 children/adolescents with severe haemophilia, except for 14 patients (moderate; minor) (1), to develop a global population pharmacokinetic (PK) model for eight factors VIII (FVIII).

Convalescent Plasma: Therapeutic Hope or Hopeless Strategy in the SARS-CoV-2 Pandemic

As the world faces the current SARS-CoV-2 pandemic, extensive efforts have been applied to identify effective therapeutic agents. Convalescent plasma collected from recovered patients has been a therapeutic modality employed for over a hundred years for various infectious pathogens.

Long-term Coexistence of SARS-CoV-2 with Antibody Response in COVID-19 Patients

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causing coronavirus disease 2019 (COVID-19) has spread worldwide.

Many faces of the anti-COVID immune response

The novel 2019 strain of coronavirus is a source of profound morbidity and mortality worldwide.

Longitudinal Change of SARS-Cov2 Antibodies in Patients with COVID-19

A novel coronavirus, SARS-CoV-2, has recently emerged and caused the rapid spread of COVID-19 worldwide.

Imbalanced host response to SARS-CoV-2 drives development of COVID-19

Viral pandemics, such as the one caused by SARS-CoV-2, pose an imminent threat to humanity. Because of its recent emergence, there is a paucity of information regarding viral behavior and host response following SARS-CoV-2 infection.

SARS-CoV-2 asymptomatic and symptomatic patients and risk for transfusion transmission

Oral swabs, sputum and blood samples from 18 patients with SARS-CoV-2 infection were examined using real-time reverse transcription polymerase chain reaction (RT-PCR) testing.

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Women With Congenital Hypofibrinogenemia/Afibrinogenemia: From Birth to Death

Congenital fibrinogen disorders are a group of most frequent rare coagulation disorder, characterized by deficiency and/or defects in the fibrinogen molecule.

COVID-19 and the Heart

Infection with the novel coronavirus, SARS-CoV-2, produces a clinical syndrome known as COVID-19.

2020

MAART

Impact of the Survey of Inhibitors in Plasma-Product Exposed Toddlers (SIPPET) study and its post hoc analyses on clinical practice in the United States: A survey of Haemophilia and Thrombosis Research Society members.

A recent randomized trial, the Survey of Inhibitors in Plasma-Product Exposed Toddlers (SIPPET), confirmed that exposure to recombinant FVIII (rFVIII) products doubled the risk of inhibitor development compared to plasma-derived FVIII (pdFVIII) in previously untreated (or minimally treated) patients (PUPs) with severe haemophilia A.

Assessing the potential cost-effectiveness of a gene therapy for the treatment of hemophilia A

Hemophilia A is a genetic, chronic disorder classified by deficient or defective coagulation factor VIII (FVIII) that puts those affected at risk for spontaneous bleeding episodes, which lead to joint damage and chronic pain over time.

The Year in Coagulation: Selected Highlights from 2019

This is the first annual highlights in coagulation article to be published in the Journal of Cardiothoracic and Vascular Anesthesia.

Hepatitis C and history of FVIII inhibitor development in a long-term cohort of Brazilian patients with haemophilia A.

Hepatitis C and history of FVIII inhibitor development in a long-term cohort of Brazilian patients with haemophilia A.

Development of Haemophilia Treatment in the Eastern Part of Germany over the Last Decade in the Kompetenznetz Hamorrhagische Diathese Ost (KHDO)

In 2005 the Kompetenznetz Hamorrhagische Diathese Ost published epidemiologic data about patients with haemophilia A (HA) and haemophilia B (HB) in the eastern part of Germany. This study provides data about the development of treatment in these patients over the past 10 years.

Clinical Evidence and Safety Profile of Emicizumab for the Management of Children with Hemophilia A

Emicizumab is a bispecific, humanized, monoclonal antibody mimicking the factor (F) VIII cofactor activity in mediating the generation of FXa by FIXa in patients with hemophilia A (HA).

Advances in Understanding Mechanisms of Thrombophilic Disorders

Venous thromboembolism constitutes a major medical problem afflicting millions of individuals worldwide each year.

Advances in knowledge of inhibitor formation in severe haemophilia A

Anti-drug antibody formation following factor VIII (FVIII) replacement therapy is the most important treatment-related complication in patients with severe haemophilia A.

Switching toward the use of recombinant factor VIII Fc fusion protein Study among 30 patients with severe hemophilia A

Only a few studies on real-world clinical use of recombinant factor VIII -fusionned with Fc (rFVIIIFc, efmoroctocog alpha) have been performed to date, with data on the annual bleeding rate (ABR), the prophylaxis regimen, and FVIII consumption.

Multicentre pharmacokinetic evaluation of rFVIII-Fc (efmoroctocog alfa) in a real life and comparison with non-extended half-life FVIII concentrates

The use of enhanced half-life (EHL) FVIII has improved the quality of prophylaxis in haemophilia A, but with a benefit that may vary from one patient to another.

Hemophilia prophylaxis adherence and bleeding using a tailored, frequency-escalated approach: The Canadian Hemophilia Primary Prophylaxis Study

Standard of care for persons with severe hemophilia A includes regular replacement of factor VIII (FVIII).

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Association between fluid creep and infection in burned children: A cohort study

Aggressive fluid resuscitation has been extensively discussed after the establishment of fluid creep phenomenon as a morbidity and mortality factor in burn children.

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Effect of Fibrinogen concentrate administration on early mortality in traumatic hemorrhagic shock: a propensity score analysis

Fibrinogen concentrate is widely used in traumatic hemorrhagic shock despite weak evidence in the literature.

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Mortality and Factors Associated With Hemorrhage During Pediatric Extracorporeal Membrane Oxygenation.

To quantify and identify factors associated with bleeding events during pediatric extracorporeal membrane oxygenation.

Patients with hemophilia A and inhibitors: prevention and evolving treatment paradigms

Novel non-replacement therapies (e.g. emicizumab) have improved the management of patients with hemophilia A with and without inhibitors while introducing new challenges and increasing the complexity of clinical decision-making.

New Patient-Centric Approaches to the Management of Alpha-1 Antitrypsin Deficiency

Alpha-1 antitrypsin deficiency (AATD) is a rare and underdiagnosed genetic predisposition for COPD and emphysema and other conditions, including liver disease.

Gene therapy 1.0 in haemophilia: effective and safe, but with many uncertainties

Gene therapy 1.0 in haemophilia: effective and safe, but with many uncertainties

Physiological Roles of the von Willebrand Factor-Factor VIII Interaction

Von Willebrand factor (VWF) and coagulation factor VIII (FVIII) circulate as a complex in plasma and have a major role in the hemostatic system.

An evaluation of the safety and efficacy of turoctocog alfa for hemophilia A

Hemophilia A is an inherited disorder that is characterized by decreased or absent factor (F)VIII and an increased risk of bleeding.

Prediction of the haemostatic effects of bypassing therapy using comprehensive coagulation assays in emicizumab prophylaxis-treated haemophilia A patients with inhibitors

In emicizumab prophylaxis, the concomitant therapy using bypassing agents (BPAs) is required for breakthrough bleeding and invasive procedures with attention to thrombotic complications.

Could Intravenous Immunoglobulin Collected from Recovered Coronavirus Patients Protect against COVID-19 and Strengthen the Immune System of New Patients?

The emergence of the novel coronavirus in Wuhan, China, which causes severe respiratory tract infections in humans (COVID-19), has become a global health concern.

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Observational Safety Study of Clottafact((R)) Fibrinogen Concentrate: Real-World Data in Mexico

The use of fibrinogen concentrate to treat or prevent major bleeding with regard to potential adverse reactions has not been free of controversy.

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Whole Blood for Civilian Urban Trauma Resuscitation: Historical, Present, and Future Considerations

Whole blood (WB) has been used for more than a century for far-forward combat resuscitation.

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The effect of fibrinogen concentrate on postoperative blood loss: A systematic review and meta-analysis of randomized controlled trials

Low level of fibrinogen is a risk factor of perioperative bleeding, which is a major complication in surgical patients. However, the safety and efficacy of fibrinogen supplementation with fibrinogen concentrate to minimize postoperative bleeding remains unclear.

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Platelets and Fibrinogen: Emerging Complexity in Trauma-Induced Coagulopathy

Trauma induces a change in nearly every observable aspect of hemostasis, generally tipping the balance toward trauma-induced coagulopathy (TIC) and bleeding in the critical early stages.

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Fibrinogen Concentrate use in routine practice in an academic hospital: A retrospective study about the effects of Fibrinogen Concentrate administration on biological parameters.

Fibrinogen Concentrate use in routine practice in an academic hospital: A retrospective study about the effects of Fibrinogen Concentrate administration on biological parameters.

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Viscoelastic haemostatic assays and fibrinogen in paediatric acute traumatic coagulopathy: A comprehensive review

Haemorrhage in paediatric trauma remains a significant cause of morbidity and mortality. Over recent years there has been increasing attention to the role of fibrinogen in traumatic haemorrhage and the association of low fibrinogen levels with poor patient outcomes.

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Missing regions within the molecular architecture of human fibrin clots structurally resolved by XL-MS and integrative structural modeling

Upon activation, fibrinogen forms large fibrin biopolymers that coalesce into clots which assist in wound healing.

2020

FEBRUARI

von Willebrand factor and factor VIII in a healthy Brazilian population. Association with ABO blood groups

von Willebrand factor and factor VIII in a healthy Brazilian population. Association with ABO blood groups

Benefits and limitations of extended plasma half-life factor VIII products in hemophilia A

Primary prophylaxis with FVIII is the therapeutic regimen of choice in severe hemophilia A; it reduces joint bleeding and associated chronic damage and helps prevent fatal bleeds.

Thrombin generation in plasma of patients with haemophilia A and B with inhibitors: Effects of bypassing agents and antithrombin reduction

Antithrombin (AT) reduction has been shown to improve thrombin generation (TG) in haemophilia with or without inhibitors.

Emicizumab in Hemophilia A

Emicizumab in Hemophilia A

Developing BIVV001, a new class of factor VIII replacement for hemophilia A that is von Willebrand factor-independent

Factor VIII (FVIII) replacement products enable comprehensive care in hemophilia A.

Hemophilia therapy: the future has begun

The success story of hemophilia care first materialized in the 1970s, when the availability of plasma-derived concentrates of coagulation factor VIII (FVIII) and factor IX (FIX) made possible the effective treatment of bleeding in patients with hemophilia A and B.

Intravenous immunoglobulin for preventing infection in preterm and/or low birth weight infants

Nosocomial infections continue to be a significant cause of morbidity and mortality among preterm and/or low birth weight (LBW) infants.

Immune globulin subcutaneous, human 20% solution (Xembify(R)), a new high concentration immunoglobulin product for subcutaneous administration

Immune globulin subcutaneous, human 20% solution (IGSC-C 20%, Xembify(R))-a new 20% immunoglobulin (IgG) liquid product for subcutaneous (SC) administration-has been developed by Grifols.

2020

JANUARI

Investigational drugs to treat hemophilia

Hemophilia A and B are congenital bleeding disorders.

Clinical controversies in anticoagulation monitoring and antithrombin supplementation for ECMO

During extracorporeal membrane oxygenation (ECMO), a delicate balance is required to titrate systemic anticoagulation to prevent thrombotic complications within the circuit and prevent bleeding in the patient.

Acquired von Willebrand Syndrome in Pediatric Extracorporeal Membrane Oxygenation: Sheared and Cleaved Everywhere, but What to Do About It?

Acquired von Willebrand Syndrome in Pediatric Extracorporeal Membrane Oxygenation: Sheared and Cleaved Everywhere, but What to Do About It?

Re-personalization and stratification of hemophilia care in an evolving treatment landscape

Hemophilia therapeutics are evolving rapidly. Comprehensive care must also evolve to embrace this change.

Factor VIII: Perspectives on Immunogenicity and Tolerogenic Strategies

Therapeutic treatment of bleeds with FVIII can lead to an antibody response that effectively inhibits its function.

Benefits and limitations of extended plasma half-life factor VIII products in hemophilia A

Primary prophylaxis with FVIII is the therapeutic regimen of choice in severe hemophilia A; it reduces joint bleeding and associated chronic damage and helps prevent fatal bleeds.

Tolerating Factor VIII: Recent Progress

Development of neutralizing antibodies against biotherapeutic agents administered to prevent or treat various clinical conditions is a longstanding and growing problem faced by patients, medical providers and pharmaceutical companies.

A sticky proposition: The endothelial glycocalyx and von Willebrand factor

Von Willebrand factor (VWF) is a critical component of the hemostatic system.

Acquired hemophilia

Acquired hemophilia (AH) is an autoimmune hemostatic disorder mediated by autoantibodies directed against factor VIII: C.

The role of genetics in the pathogenesis and diagnosis of type 1 Von Willebrand disease

Purpose of review Von Willebrand disease (VWD) is a common bleeding disorder, but diagnosis of VWD is challenging, particularly with type 1 VWD.

In Vitro Assessment of von Willebrand Factor in Cryoprecipitate, Antihemophilic Factor/VWF Complex (Human), and Recombinant von Willebrand Factor

Patients with von Willebrand disease (VWD) often require treatment with supplemental von Willebrand factor (VWF) prior to procedures or to treat bleeding.

Comparison of antithrombin III products in pediatric patients receiving extracorporeal membrane oxygenation

The study investigated the safety and efficacy of two antithrombin III (ATIII) products in pediatric patients receiving extracorporeal membrane oxygenation (ECMO) by performing a retrospective analysis of patients who received either recombinant ATIII (rATIII) or human-derived ATIII (hATIII).

The Current Understanding of Molecular Pathogenesis of Quantitative von Willebrand Disease, Types 1 and 3

Von Willebrand disease (VWD), the most prevalent congenital bleeding disorder, arises from deficiencies in quantity or quality of von Willebrand factor (VWF).

Perioperative safety and haematostatic efficacy of a new bypassing agent pd-FVIIa/FX (Byclot) in haemophilia patients with high-responding type inhibitors

The novel agent pd-FVIIa/FX is a 1 : 10 protein weight mixture of activated factor VII (FVIIa) and factor X (FX) derived from donated blood plasma.

Therapeutic innovations for hemophilia

The current treatment of haemophilia relies on intravenous administration several times a week of clotting factors VIII (FVIII) or IX (FIX) concentrates, either derived from plasma or produced by biotechnology.

Molecular Mechanisms of Inhibitor Development in Hemophilia

The development of neutralizing antibodies in hemophilia is a serious complication of factor replacement therapy.

The cost of hemophilia treatment: the importance of minimizing it without detriment to its quality

Hemophilia is a very expensive disease. Ameliorations in the management of hemophilia cause increased patient survival, more complex disease management, and augmented treatment costs.

Von Willebrand Disease: From In Vivo to In Vitro Disease Models

Von Willebrand factor (VWF) plays an essential role in primary hemostasis and is exclusively synthesized and stored in endothelial cells and megakaryocytes.

Clinical Approach to Manage Gastrointestinal Bleeding with a Left Ventricular Assist Device (LVAD)

Left ventricular assist devices (LVADs) are an exceedingly important form of mechanical support for patients with end-stage heart failure.

Multiyear Follow-up of AAV5-hFVIII-SQ Gene Therapy for Hemophilia A

Adeno-associated virus (AAV)-mediated gene therapy is under investigation as a therapeutic option for persons with hemophilia A. Efficacy and safety data include 3 years of follow-up after a single administration of AAV5-hFVIII-SQ.

Cost-Effectiveness and Budget Impact of Emicizumab Prophylaxis in Haemophilia A Patients with Inhibitors

Recent evidence demonstrated that weekly prophylaxis with subcutaneous bispecific antibody (emicizumab) has shown higher efficacy in adolescent and adults patients affected by haemophilia A (HA) with inhibitor, compared with patients treated on demand or on prophylaxis with bypassing agents (BPAs).

Genetic Background of von Willebrand Disease: History, Current State, and Future Perspectives

Sequencing of the gene encoding for von Willebrand factor (VWF) has brought new insight into the physiology of VWF as well as its pathophysiology in the context of von Willebrand disease (VWD).

Activated prothrombin complex concentrate (FEIBA®) in acquired haemophilia A: a large multicentre Italian study - the FAIR Registry

This study aimed to assess dosage, duration of treatment, as well as the effectiveness and safety of activated prothrombin complex concentrate (aPCC) in patients with AHA.

Assessing prophylactic use and clinical outcomes in hemophilia A patients treated with rVIII-SingleChain and other common rFVIII products in Germany

To evaluate real-world outcomes with rVIII-SingleChain and other commonly used recombinant FVIII (rFVIII) products.

Factor VIII: the protein, cloning its gene, synthetic factor and now - 35 years later - gene therapy; what happened in between?

The foundation of haemophilia A therapy in the last 35 years has been critically dependent on isolation of the Factor VIII (FVIII) protein and discovery of the cDNA sequence of the FVIII gene, published in 1984.

Factor VIII replacement is still the standard of care in haemophilia A

Prophylactic factor VIII (FVIII) has dramatically improved haemophilia A treatment, preventing joint bleeding and halting the deterioration of joint status.

Progress in Hematopoietic Stem Cell Transplantation for CIDP

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a kind of autoimmune-mediated inflammation and demyelinating disease.

Current treatment practice of Guillain-Barre syndrome

To define the current treatment practice of Guillain-Barré syndrome (GBS).

Differences in Patient Demographics and Healthcare Costs of Patients with PIDD Receiving Intravenous or Subcutaneous Immunoglobulin Therapies in the United States.

Primary immune-deficiency disease (PIDD) is a rare, debilitating disease of the immune system that predisposes the affected individual to infection, autoimmune conditions, and neoplasm.

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Fibrinogen Supplementation and Its Indications

Adequate plasma levels of fibrinogen are essential for clot formation, and in severe bleeding, fibrinogen reaches a critically low plasma concentration earlier than other coagulation factors.

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Obstetrical and postpartum complications in women with hereditary fibrinogen disorders: A systematic literature review

Hereditary fibrinogen disorders (HFD) are rare quantitative or qualitative fibrinogen anomalies, including afibrinogenaemia (A), hypofibrinogenaemia (H), dysfibrinogenaemia (D) and hypodysfibrinogenaemia (HD).

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Lactate and fibrinogen as good predictors of massive transfusion in postpartum hemorrhage.

This study aims to identify the clinical factors that can predict the requirement of massive transfusion among patients with postpartum hemorrhage (PPH)

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Thromboelastography-targeted management of severe coagulopathy and off-label use of four-factor prothrombin complex concentrate in an infant with massive bleeding

A 4-month-old girl initially presented to the pediatric ICU at 9 days old with multiorgan failure and cerebellar hemorrhage secondary to disseminated enteroviral infection and was eventually listed for liver transplant.

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Clotting factors: Clinical biochemistry and their roles as plasma enzymes

The purpose of this review is to describe structure and function of the multiple proteins of the coagulation system and their subcomponent domains.

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Effects of Post-Translational Modifications of Fibrinogen on Clot Formation, Clot Structure, and Fibrinolysis: A Systematic Review.

Post-translational modifications of fibrinogen influence the occurrence and progression of thrombotic diseases.

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Early administration of fibrinogen concentrate is associated with improved survival among severe trauma patients: a single-centre propensity score-matched analysis.

Fibrinogen plays an important role in haemostasis during the early phase of trauma, and low fibrinogen levels after severe trauma are associated with haemostatic impairment, massive bleeding, and poor outcomes.

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Fibrinogen concentrate for treatment of bleeding and surgical prophylaxis in congenital fibrinogen deficiency patients

Congenital fibrinogen deficiency is an ultra-rare disorder where patients can experience severe and/or frequent bleeding episodes (BEs). Here, we present the largest prospective study to date on the treatment of this disorder.

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Perioperative fluid management for major elective surgery

Adequate fluid balance before, during and after surgery may reduce morbidity. This review examines current concepts surrounding fluid management in major elective surgery.

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The prophylactic use of fibrinogen concentrate in high-risk cardiac surgery

Perioperative blood loss is a major contributor to morbidity and mortality in cardiac surgery. Plasma fibrinogen levels play an essential role in hemostasis and deplete quickly during hemorrhage.

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Thromboelastometry assessment of the effects of fibrinogen, activated prothrombin complex concentrate, and tranexamic acid on clot formation and fibrinolysis in a model of trauma-induced coagulopathy

Coagulation abnormalities are common following major trauma. The aim of this study was to assess the improvement of trauma-induced coagulopathy (TIC) in an in vitro model.

Vonicog alfa for the management of von Willebrand disease: a comprehensive review and single-center experience

Von Willebrand Disease (VWD) is characterized by a qualitative or quantitative defect in von Willebrand factor that results in prolonged bleeding due to the inability to form a stable platelet plug.

2019

DECEMBER

Therapeutic antibodies in hemostasis. From the past to the future

L’hémostase est un processus complexe qui implique de nombreux acteurs cellulaires et moléculaires.

Factors associated with headache in intravenous immunoglobulin treatment for neurological diseases.

To identify possible risk factors influencing the incidence of intravenous immunoglobulin (IVIg) treatment-related cephalalgia in neurological diseases.

Immunosuppressive and Immunomodulatory Therapies for Neuromuscular Diseases Part I: Traditional Agents

Immunosuppressive and immunomodulatory therapies have had a major effect on the treatment of immune-mediated neuromuscular diseases.

The changing face of immune tolerance induction in haemophilia A with the advent of emicizumab

Introduction: As a result of the new treatment paradigm that the haemophilia community will face with the availability of novel (non‐factor) therapies, an updated consensus on ITI recommendations and inhibitor management strategies is needed.

Randomized, controlled crossover study of IVIg for demyelinating polyneuropathy and diabetes

Objective: To determine whether IV immunoglobulin (IVIg) is more effective than placebo at reducing disability in patients with diabetes and demyelinating polyneuropathy features.

2019

NOVEMBER

Acquired von Willebrand syndrome in patients on long-term left ventricular assist device support: Results of a Belgian center

This long-term follow-up study shows that aVWS is not only present early after LVAD implantation but persists over time.

Current treatment practice of Guillain-Barré syndrome

Define the current treatment practice of Guillain-Barré syndrome (GBS).

New therapies for von Willebrand disease

The management of von Willebrand disease (VWD) is based upon the dual correction of the primary hemostasis and of the secondary defect of factor VIII coagulant activity (FVIII:C).

2019

OKTOBER

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Peri-procedural hemostasis disorders in surgical and transcatheter aortic valve implantation

Despite their high effectiveness, surgical aortic valve replacement (AVR) and transcatheter aortic valve implantation (TAVI) are associated with substantial risk of bleeding.

Comparison of IVIg 5% Versus 10% in hematological patients with a secondary immunodeficiency disorder

The aim of this study was to evaluate the administration of intravenous immunoglobulin (IVIg) solutions (5% vs. 10%) in hematological patients suffering from a secondary immunodeficiency (SID) to optimize infusion duration and hospitalization time.

Deaths Associated with Emicizumab in Patients with Hemophilia A

Letter to the editor

Acquired von Willebrand Syndrome in Pediatric Extracorporeal Membrane Oxygenation Patients: A Single Institution’s Experience

Describes the prevalence of acquired von Willebrand syndrome in pediatric patients undergoing extracorporeal membrane oxygenation deemed to be at increased risk for the disease in our institution.

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New Hemostatic Agents: Perioperative Anesthetic Considerations

Pharmacologic agents with procoagulant effects and antidotes against antithrombotic drugs play an important role in the prevention and management of perioperative coagulopathic bleeding

2019

SEPTEMBER

von Willebrand factor alloantibodies in type 3 von Willebrand disease

The development of neutralizing antibodies is a rare complication of von Willebrand disease treatment.

BMI is an important determinant of VWF and FVIII levels and bleeding phenotype in patients with von Willebrand disease

Higher BMI is associated with higher VWF and FVIII levels in patients with type 1 and type 2 VWD, compared to normal weight VWD patients.

2019

AUGUSTUS

The evolution of factor VIIa in the treatment of bleeding in haemophilia with inhibitors

The use of activated factor VII (FVIIa) for the treatment of bleeding events in haemophilia patients with inhibitors was first reported over 30 years ago.

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Accuracy of a Rapid Diagnostic Test for the Presence of Direct Oral Factor Xa or Thrombin Inhibitors in Urine—A Multicenter Trial

The rapid determination of the presence of direct oral anticoagulants (DOACs) in a patient remains a major challenge in emergency medicine and for rapid medical treatment decisions.

2019

JULI

Haemostasis in oral surgical procedures involving patients with a ventricular assist device

The purpose of this study was to determine whether tooth extraction for patients with ventricular assist devices (VADs) could be performed without interruption of anticoagulant and/or antiplatelet therapy and whether treatment with von Willebrand factor concentrates and desmopressin is required.

Pre‑procedural abnormal function of von Willebrand Factor is predictive of bleeding after surgical but not transcatheter aortic valve replacement

Both transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement (SAVR) have been proven to effectively correct von Willebrand Factor (vWF) pathologies, however there is limited data simultaneously comparing outcomes of both approaches.

How we make an accurate diagnosis of von Willebrand disease

von Willebrand disease (VWD) is a common autosomally inherited hemorrhagic disorder mainly associated with mucocutaneous bleeding.

2019

JUNI

Management of bleeding and invasive procedures in haemophilia A patients with inhibitor treated with emicizumab (Hemlibra®): Proposals from the French network on inherited bleeding disorders (MHEMO), the French Reference Centre on Haemophilia, in collaboration with the French Working Group on Perioperative Haemostasis (GIHP)

Emicizumab (Hemlibra®) recently became available and requires an adaptation for managing bleeding, suspected bleeding and emergency or scheduled invasive procedures in haemophilia A patients with inhibitor.

2019

MEI

Retrospective correlation analysis of plasma Immunoglobulin G and clinical performance in CIDP

Chronic inflammatory demyelinating polyneuropathy (CIDP) can be successfully treated with immunoglobulin either intravenously (IVIG) or subcutaneously (SCIG).

Replacement Therapy in Patients with Von Willebrand Disease—Indications and Monitoring

In patients with von Willebrand disease (VWD), replacement therapy may be indicated in the case of spontaneous bleeding, surgical interventions and injuries/trauma or as a prophylaxis of spontaneous bleeding episodes.

2019

APRIL

von Willebrand factor sialylation—A critical regulator of biological function

von Willebrand factor (VWF) undergoes complex post‐translational modification prior to its secretion into the plasma.

Gastrointestinal angiodysplasia in two patients with type 3 von Willebrand disease

Angiodysplastic (AD) lesion is the most common cause of recurrent gastrointestinal (GI) bleeding in inherited Von Willebrand disease (VWD) patients lacking high-molecularweight multimers.

2019

FEBRUARI

Inhibitors: A Need for Eradication?

The development of inhibitors against factor VIII (FVIII) concentrates represents a significant treatment complication for hemophilia.

2019

JANUARI

Optimization of von Willebrand factor multimer analysis in vertical mini-gel electrophoresis systems: A rapid procedure

Von Willebrand disease (VWD) is a common cause of bleeding worldwide.

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