Platelet adhesion receptors: novel targets for anti-thrombotic therapy

The critical role of platelets in the development of the acute coronary syndromes is now well recognised, and a great deal of effort has therefore focused on elucidating the key adhesion receptors mediating platelet-vessel wall and platelet-platelet interactions. The vascular adhesion protein von Willebrand factor (vWf) plays a key role in supporting platelet adhesion to the damaged vessel wall and binds to two adhesion receptors on the platelet surface, the glycoprotein (GP) Ib-V-IX complex and glycoprotein IIb-IIIa. The GP Ib-V-IX complex is a unique adhesion receptor which enables platelets to roll on a vWf matrix under conditions of rapid blood flow as well as transducing signals leading to the activation of GP IIb-IIIa. This latter receptor binds to a distinct site on vWf and is essential for stabilising platelet adhesion to the site of vessel wall injury. In addition to supporting platelet adhesion, GP IIb-IIIa plays a key role in a number of other platelet responses including platelet spreading, aggregation, the release of procoagulant-rich microvesicles, and clot retraction. Given its central role in platelet function GP IIb-IIIa has become an attractive target for the development of novel anti-thrombotic agents. In this paper, we consider the advantages of inhibitors of GP IIb-IIIa compared with other established anti-platelet drugs including aspirin and ticlopidine, and also discuss some potential problems associated with the inhibition of GP IIb/IIIa and other platelet adhesion receptors.