Von Willebrand Disease

Von Willebrand disease (VWD) is the most common inherited bleeding disorder, affecting approximately 1% of the general population (though clinically significant disease is less prevalent). It is caused by quantitative or qualitative deficiency of von Willebrand factor (VWF), a large multimeric glycoprotein that plays two essential roles in hemostasis: platelet adhesion and coagulation factor VIII protection. Under normal hemostatic conditions, when a blood vessel is injured, subendothelial collagen is exposed. VWF is released from Weibel-Palade bodies in endothelial cells and alpha-granules in platelets. The released VWF binds to exposed collagen and undergoes conformational change under the shear stress of flowing blood, exposing binding sites for the platelet glycoprotein Ib/IX/V (GPIb) receptor. This VWF bridge between collagen and platelets is the primary mechanism for platelet adhesion at sites of vascular injury, especially in areas of high shear stress such as arteries and the microvasculature. Without adequate VWF, platelets cannot adhere properly to the injured vessel wall, resulting in impaired primary hemostasis. VWF also serves as a carrier protein for coagulation factor VIII, protecting it from premature degradation by activated protein C...