Von Willebrand's disease and the mechanisms of platelet function.

Abstract

Von Willebrand's disease, the most common congenital bleeding disorder in humans, is the consequence of quantitative and/or qualitative defects of von Willebrand factor, a protein necessary for platelet adhesion and thrombus formation at sites of vascular injury. The definition of the molecular basis of von Willebrand's disease has helped clarify the structure of von Willebrand factor as well as its essential role in platelet function, particularly under haemodynamic conditions of high shear stress. Platelets respond rapidly to alterations of endothelial cells by attaching firmly to the site of lesion, where exposure of subendothelial components may have occurred. The first layer of platelets is in contact with the thrombogenic surface (adhesion), whereas subsequent growth of the haemostatic plug depends on platelet-platelet interactions (aggregation). Both aspects of platelet function are influenced by von Willebrand factor binding to specific platelet membrane receptors as well as subendothelial structures, such as collagen.