Historical, current and future treatments for von Willebrand disease

Sep 29, 2026

Uploaded by Miles

Von Willebrand disease (VWD) is a heterogeneous inherited bleeding disorder with a wide range of symptoms that are difficult to identify and quantify. Despite major progress in understanding its pathophysiology, diagnosis and management remain challenging. This review surveys the therapeutic landscape, critically evaluating long-standing replacement therapy supported by clinical evidence and examining emerging preclinical options and their mechanisms. Historical treatments, recent advances, and future prospects are compared, with attention to replacement products, desmopressin, recombinant VWF, and investigational therapies addressing unmet patient needs.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages13

Reading Time33 min

AccessFree to download

Abstract

Introduction

Plasma-derived products to treat von Willebrand disease

REVIEW SERIES Historical, current and future treatments for von Willebrand disease Caterina Casari,1 Frank W.G. Leebeek2 and Flora Peyvandi3,4 1 Université Paris-Saclay, INSERM, Hémostase Inflammation Thrombose HITh U1176, Le Kremlin-Bicêtre, France, 2 Department of Hematology, Erasmus University Medical Center, Rotterdam, the Netherlands, 3 IRCCS Ca’ Granda Ospedale Maggiore Policlinico Foundation, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milan, Italy and 4 Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy Correspondence: C. Casari [caterina.casari@inserm.fr](caterina.casari@inserm.fr) [Received:](Received: May 30)[ May 30](Received: May 30), 2025. Accepted: August 1, 2025. [https://doi.org/10.3324/haematol.2024.286037](https://doi.org/10.3324/haematol.2024.286037) ©2026 Ferrata Storti Foundation Published under a CC BY-NC license Abstract Von Willebrand disease (VWD) is a heterogeneous group of defects characterized by a spectrum of bleeding symptoms ranging from mild to severe, which remain difficult to identify and assess quantitatively. Despite significant advances in our understanding of the pathophysiology of the disease, diagnosis and management remain challenging. This review examines the therapeutic landscape for VWD, discussing historical treatments, recent advancements and prospects. Decades of clinical evidence supporting the efficacy of replacement therapy will be critically presented, and preclinical data for emerging options will be examined. For many years, the standard of care for VWD has involved replacement therapy with blood-derived products and desmopressin. The introduction of recombinant von Willebrand factor represents a more recent development compared to other recombinant factors, and its use in certain populations of patients is still under investigation. Despite being relatively new, innovative therapeutic options are being explored and developed to address patients’ unmet needs. Some of these therapies are currently undergoing or nearing clinical evaluation, while others remain in the preclinical phase of development. After years of neglected attention, innovation in the treatment of VWD is now rapidly expanding. Introduction Von Willebrand disease (VWD) is the most prevalent inherited bleeding disorder, affecting up to 1% of the general population, although symptomatic disease is less common. It is caused by defects in von Willebrand factor (VWF), a multimeric glycoprotein essential for primary hemostasisand stabilization of coagulation factor VIII (FVIII) .1 VWD results from quantitative deficiencies (types 1 and 3) or qualitative defects (type 2) of VWF.2,3 Type 1, the most common form accounting for approximately 70-80% of cases, is characterized by a partial quantitative deficiency. Subtype 1C group defects are associated with increased clearance of VWF. Type 2 includes subtypes 2A, 2B, 2M, and 2N, each with a different qualitative defect in VWF function. Type 3 is the rarest and most severe form, marked by a near-total absence of VWF, often associated with severely reduced FVIII levels. Symptoms range from mild mucocutaneous bleeding (e.g., epistaxis, menorrhagia) to life-threatening hemorrhages in severe forms. The diagnosis involves assessment of personal and familial bleeding history and specialized laboratory assays measuring VWF antigen (VWF:Ag) and activity (VWF:RCo or more recent activity tests), and FVIII activity (FVIII:C) . For the past two decades, treatment options have primarily focused on replacement strategies with plasma-derived (pd) and recombinant (r) VWF, or with desmopressin (DDAVP), which induces the release of VWF (and FVIII) from intracellular storage granules within endothelial cells, resulting in a temporary rise of the protein concentrations in circulation. Additional approaches, not specific to VWD, include antifibrinolytics and hormonal therapies. In contrast to the

FAQs

What is von Willebrand disease (VWD), and why is it difficult to assess?

VWD is a heterogeneous inherited bleeding disorder with symptoms ranging from mild to severe. Even with advances in pathophysiology, it remains difficult to identify and assess quantitatively.

What treatments are considered standard care for VWD?

Standard care includes replacement therapy using blood-derived products and desmopressin (DDAVP), which temporarily increases circulating VWF (and FVIII) by inducing release from endothelial storage granules.

Which emerging therapies are discussed for future VWD management?

The review discusses innovative strategies aiming to enhance or correct specific molecular defects in VWF function. It also covers recombinant VWF use in selected patient populations under investigation, along with other therapies progressing toward or nearing clinical evaluation or remaining at the preclinical stage.

Sep 29, 2026

Uploaded by Miles