von Willebrand Factor (vWF) is a high molecular weight multimeric (1-20 X 10(6) daltons) glycoprotein which is absent or inactive in von Willebrand's disease (vWD). It is synthesized by the endothelial cell under the control of an autosome and may be released into the blood stream as well as into the subendothelium (SE). vWF is also synthesized by the megacaryocyte and localized in the alpha granules of platelets. Platelet vWF is released during aggregation. Platelets do not adhere to intact endothelial cells but interact with the SE in case of vessel wall injury. vWF plays a key role in platelet adhesion to the SE, especially at high shear rate conditions which prevail in the microcirculation. This function is confirmed by the decreased platelet adhesion observed in either vWD blood (corrected by vWF) or normal blood in the presence of polyclonal or monoclonal antibodies to vWF. The mechanism of platelet adhesion to the SE is still poorly understood. vWF only acts at high shear, ie when the flow rate is elevated and the time of interaction between platelets and the vessel wall is short. This large protein could serve as a "bridge" between the platelet membrane and the SE. It has been shown to bind first to the SE prior to platelet adhesion. Platelet and endothelial cell vWF probably also interact since they may be released in high concentration at the site of injury. The nature of the SE component to which vWF and platelets bind is unknown. Among the candidates are the basement membrane and the collagen fibers (which adsorb vWF), fibronectin, and the microfibrils (which induce vWF-mediated platelet aggregation). It is thus possible that a receptor for vWF exists on one of these components. The ristocetin-induced platelet membrane receptor for vWF seems to be glycoprotein Ib, platelet adhesion being also abnormal in Giant Platelet Syndrome. The in vivo counterpart for ristocetin is unknown, but it is possible that collagen, microfibrils, thrombin (which also induces the platelet receptor for vWF or sialidases (asialo-human vWF is able to directly bind to the platelet membrane) could replace ristocetin. Several sources of data suggest that carbohydrate is important in vWF-platelet interaction.