Hemophilia management: Huge impact of a tiny difference

Authors: Kloosterman, F., Zwagemaker, A. F., Abdi, A., Gouw, S., Castaman, G., and Fijnvandraat, K.

Publication: Res Pract.Thromb Haemost; 4,3:377-385. April 2020

Affiliations: Pediatric Hematology Amsterdam UMC Emma Children’s Hospital University of Amsterdam Amsterdam The Netherlands; Department of Clinical Epidemiology Leiden University Medical Center Leiden The Netherlands; Department of Oncology Center for Bleeding Disorders Careggi University Hospital Florence Italy; Department of Molecular Cellular Hemostasis Sanquin Research Amsterdam The Netherlands.

Abstract: Hemophilia A and B are inherited X-linked disorders of hemostasis, associated with an increased bleeding tendency. Patients with severe hemophilia have undetectable clotting factor levels and experience spontaneous bleeds. In patients with nonsevere hemophilia, the clotting factor levels are 2% to 40% of normal and bleeds predominantly occur after provocative events such as trauma and surgery. Despite this milder phenotype, patients with nonsevere hemophilia may suffer from considerable morbidity and have an increased mortality risk. However, many aspects of the course of disease and treatment remain unclear. Information on the factors influencing interindividual differences in bleeding phenotype is lacking, and misdiagnosis may occur due to assay discrepancies in the diagnostic workup. Desmopressin is the preferred treatment modality, but some patients and indications require treatment with clotting factor concentrates. This may elicit inhibitor formation, which is associated with an increased burden of disease and a higher mortality rate. It has been found that patients with nonsevere hemophilia A carry a lifelong risk for this serious complication. In this review, we provide an overview of the current knowledge of the diagnosis and management of nonsevere hemophilia. A report of science presented at the International Society on Thrombosis and Haemostasis 2019 Annual Congress is also provided.