von Willebrand factor as a target for antithrombotic intervention.

Abstract

The adhesive protein von Willebrand factor is essential for the formation of platelet thrombi under flow conditions characterized by high shear stress. This function requires the interaction with two distinct platelet receptors, the glycoprotein complexes Ib-IX-V and IIb-IIIa. Interaction with the former results in platelet activation, a necessary step for binding to the latter and supporting stable aggregation. The inhibition of von Willebrand factor binding to glycoprotein Ib can be achieved with small recombinant fragments containing the specific functional domain of the molecule that interacts with this platelet receptor. Such fragments may provide a new selective approach to antithrombotic therapy.