Platelet adhesion receptors: novel targets for anti-thrombotic therapy

The critical role of platelets in the development of the acute coronary syn dromes is now well recognised, and a great deal of effort has therefore foc used on elucidating the key adhesion receptors mediating platelet-vessel wa ll and platelet-platelet interactions. The vascular adhesion protein von Wi llebrand factor (vWf) plays a key role in supporting platelet adhesion to t he damaged vessel wall and binds to two adhesion receptors on the platelet surface, the glycoprotein (GP) Ib-V-IX complex and glycoprotein IIb-IIIa. T he 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 tr ansducing signals leading to the activation of GP IIb-IIIa. This latter rec eptor binds to a distinct site on vWf and is essential for stabilising plat elet 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 platel et responses including platelet spreading, aggregation, the release of proc oagulant-rich microvesicles, and clot retraction. Given its central role in platelet function GP IIb-IIIa has become an attractive target for the deve lopment of novel anti-thrombotic agents. In this paper, we consider the adv antages of inhibitors of GP IIb-IIIa compared with other established anti-p latelet drugs including aspirin and ticlopidine, and also discuss some pote ntial problems associated with the inhibition of GP IIb/IIIa and other plat elet adhesion receptors.