Von Willebrand factor as a therapeutic target in thrombotic disorders

Abstract

Von Willebrand factor (VWF) plays an important role in primary hemostasis. Dysregulated plasma VWF levels are implicated in various pathological conditions. Reduced or dysfunc tional WF is associated with bleeding, known as von Willebrand disease. Whereas elevated plasma WF levels may give rise to an increased risk of developing arterial thrombotic events. In general, antithrombotic strategies in arterial thrombosis primarily focus on inhibiting platelet aggregation; however, treatment failure, antiplatelet drug resistance, and adverse bleeding tendencies underscore the necessity for the development of more efficacious and safer therapeutic modalities. Targeting WF presents an interesting therapeutic approach as it operates independently of platelet activation pathways for platelet-rich thrombus forma-tion. Over time, several VWF inhibitors have progressed to clinical application for thrombosis management, with ongoing research endeavors exploring novel compounds targeting WF. This review provides a comprehensive overview of the evolution of WF-targeting therapeu tic agents, elucidating their current developmental stages, clinical indications, and evaluating their respective advantages and limitations.