Physiological Roles of the von Willebrand Factor-Factor VIII Interaction

Authors: Kiouptsi, K. and Reinhardt, C.

Publication: Subcell Biochem; 94,437-464. March 2020

Affiliations: Center for Thrombosis and Hemostasis (CTH), University Medical Center Mainz, Langenbeckstrasse 1, Building 708, 55131, Mainz, Germany; German Center for Cardiovascular Research (DZHK), Partner Site RheinMain, Mainz, Germany.

Abstract: Von Willebrand factor (VWF) and coagulation factor VIII (FVIII) circulate as a complex in plasma and have a major role in the hemostatic system. VWF has a dual role in hemostasis. It promotes platelet adhesion by anchoring the platelets to the subendothelial matrix of damaged vessels and it protects FVIII from proteolytic degradation. Moreover, VWF is an acute phase protein that has multiple roles in vascular inflammation and is massively secreted from Weibel-Palade bodies upon endothelial cell activation. Activated FVIII on the other hand, together with coagulation factor IX forms the tenase complex, an essential feature of the propagation phase of coagulation on the surface of activated platelets. VWF deficiency, either quantitative or qualitative, results in von Willebrand disease (VWD), the most common bleeding disorder. The deficiency of FVIII is responsible for Hemophilia A, an X-linked bleeding disorder. Here, we provide an overview on the role of the VWF-FVIII interaction in vascular physiology.