von Willebrand factor (vWF) is a large glycoprotein of complex multimeric structure. It is synthesized exclusively by vascular endothelium and megakaryocytes, and is stored and secreted by these cell types as well as by circulating platelets. In blood, it serves not only as a carrier for factor VIII, protecting it from proteolysis, but also plays a critical role in hemostasis by promoting platelet deposition at sites of endothelial cell (EC) injury. To accomplish this task, vWF must form a “bridge” between components of the subendothelial matrix or the surface of inflamed venular endothelium and receptors expressed on circulating platelets. One remarkable feature of this plasma glycoprotein is its ability to support significant interactions with platelets only upon surface immobilization and under specific hemodynamic conditions. This avoids the disastrous consequences of platelet–vWF aggregate formation in flowing blood. The importance of vWF in hemostasis is underscored by the occurrence of clinical bleeding when plasma levels fall below 50 IU/dL or when functional defects are present in the protein due to spontaneously occurring or inherited mutations. Such abnormalities result in von Willebrand disease (vWD), the most common inherited bleeding disorder in humans, with an estimated prevalence of 1% in the general population (1,2).

HISTORICAL ASPECTS

Recognition that certain families may have a predisposition to bleeding has been described in the Talmud and other Hebrew writings as early as the second century a.d. (3). These Jewish texts decreed that offspring were exempt from circumcision if deaths due to hemorrhage occurred in other male siblings undergoing this procedure, suggesting that these individuals suffered from hemophilia.