Historical perspective and overview

For most bleeding disorders, the symptoms and clinical recognition of the disease occurred long before the biochemical characterization of the disease. A case in point is the description of von Willebrand disease by the Finnish physician Erik von Willebrand (ca. 1926) and the description of the Bernard–Soulier syndrome by French physicians, Jean Bernard and Jean-Pierre Soulier (ca. 1948). In both cases, decades would past before the molecular basis of the disease would define roles for von Willebrand factor (vWF) and the platelet receptor, glycoprotein (GP) Ib–IX–V, in hemostasis and thrombosis. Two-dimensional gel electrophoresis would associate an absent platelet glycoprotein in patients with the Bernard–Soulier syndrome; while the molecular identity of vWF would not be unequivocally established until the gene was characterized and shown to be a distinct protein circulating in a complex with blood coagulation factor VIII.

The current models of platelet adhesion to the extracellular matrix involve a number of different ligands and platelet receptors coordinated in a synergistic response to correct a vascular lesion. Nevertheless, vWF and its platelet receptors represent a major component in this response and become the exclusive ligand and receptor interaction under blood flow conditions typically found in arterioles and small arteries. Thus, under certain conditions vWFdependent thrombus formation is part of the synergistic response, yet under specific rheological conditions it becomes the sole ligand capable of initiating platelet deposition and thrombus growth.