Von Willebrand Factor and platelet interactions with the vessel wall

Abstract

von Willebrand factor (vWF) is a multimeric glycoprotein which has a dual role in haemostasis, functioning as carrier protein for Factor VIII and mediating platelet adhesion to exposed subendothelium (SE). vWF interacts with components of the SE such as collagen and heparin-like glycosaminoglycans as well as with two platelet membrane receptors: glycoprotein (GP) Ib and GPIIb/IIIa. These multiple binding functions explain its definition as an adhesive protein. vWF promotes platelet adhesion at the high shear rates which correspond to the rheologic conditions of the microcirculation or of narrowed arterial vessels. The role of the vWF-GPIb interaction in platelet adhesion is well known; that of the vWF-GPIIb/IIIa interaction has been more recently demonstrated through the use of monoclonal antibodies (MAbs) or synthetic peptides blocking vWF-binding to GPIIb/IIIa. In addition, perfusion studies in native, non-anticoagulated blood emphasize the concept that vWF is also essential for thrombus formation at high shear stress. Thus, vWF fragments, synthetic peptides or MAbs blocking the functional domains of vWF represent potential therapeutic strategies to prevent the development of thrombosis.