The role of VWF-collagen interaction in acute platelet thrombus formation

The first step in the formation of an arterial platelet thrombus consists of the interaction between collagen-bound VWF and the platelet glycoprotein Ib/IX/V complex. This event results in a further interaction of the collagen receptors with the damaged vessel wall, leading to platelet activation and platelet aggregation, a process mediated by the platelet GFIIb/IIIa receptor. Current antiplatelet agents interfering with platelet activation steps (e.g., acetylsalicylic acid, clopidogrel) or blocking the GPIIb/IIIa receptor (e.g., abciximab, eptifibatide, lamifiban, tirofiban) have proven their clinical usefulness. However, their efficacy is not optimal and therefore the search for new antiplatelet drugs continues. Here we review data on a new approach for preventing arterial thrombosis, i.e., by blocking the initial platelet adhesion step. The in vitro and in vivo antithrombotic effects of inhibiting collagen-VWF binding are summarized and the anticipated benefits of specifically interfering with this interaction are highlighted.