Increased von Willebrand Factor clearance in the pathogenesis of von Willebrand disease and the role of von Willebrand Factor glycans in modulating susceptibility to clearance in-vivo

Abstract

Von Willebrand Factor (VWF) is a multimeric, adhesive, plasma glycoprotein which plays two important roles in haemostasis, first as a carrier for the procoagulant factor VIII (FVIII) and second, as a bridge between platelets and the blood vessel wall at sites of vascular injury. Plasma VWF concentrations vary over a wide range in the normal population (50 - 200%) and inherited VWF deficiency is responsible for the most common constitutional bleeding disorder, von Willebrand disease (VWD). Intriguingly, linkage analysis of a European Type 1 VWD population showed that 30-50% of Type 1 VWD patients do not have a mutation linked to their VWF locus.