Diagnosis and Treatment of Von Willebrand Disease in 2024 and Beyond

Authors: James, Paula; Leebeek, Frank; Casari, Caterina; Lillicrap, David

Affiliations: Departments of Medicine and Pathology and Molecular Medicine, Queen’s University, Kingston, Canada. Department of Hematology, Erasmus University Medical Center, Rotterdam, The Netherlands. University Paris-Saclay, INSERM, Hemostasis Inflammation Thrombosis HITH U1176, Le Kremlin-Bicêtre, France. Department of Pathology and Molecular Medicine, Queen’s University, Kingston, Canada.

Publication: Haemophilia. 2024

ABSTRACT: MANUSCRIPT BACKGROUND AND AIM: 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. This condition is almost certainly the most common inherited bleeding disorder, and the major symptomatic burden of the disease is experienced by females during their reproductive years. Diagnosis relies on the identification of a personal and family history of excessive mucocutaneous bleeding, and laboratory features consistent with quantitative and/or qualitative abnormalities of VWF. This review focuses on three aspects of VWD management, with current updates and a look into the future. MANUSCRIPT THEMES: First, we will address the role of genetics in the diagnosis and possible therapies for VWD. With current technologies, VWD genetic diagnosis is usually confined to the confirmation of type 2 subtypes of the disease and type 3 VWD analysis for family planning. While type 3 VWD is a potential candidate for the application of gene therapy, no treatments are currently close to entering the clinic. Second, the peri-procedural management of patients with VWD remains an important element of care. The choice of product, its dose and schedule all require careful consideration depending upon the type and disruptive nature of the planned procedure. Lastly, in addition to gene therapy, several other novel therapeutic interventions are also being developed for bleeding and prophylaxis in VWD. These include a VWF aptamer interfering with VWF clearance and bioengineered forms of VWF.