FUNDAMENTALS OF COAGULATION AND GLYCOPROTEIN-IIB IIIA RECEPTOR INHIBITION/

An understanding of the coagulation process and the role of platelets is essential to recognizing the shortcomings of older anticoagulant th erapies and appreciating the clinical potential of newer Forms of anti platelet and anticoagulant therapy for acute coronary syndromes. The a nticoagulant actions of heparin are severely limited by dependence on antithrombin III, neutralization by platelet factor 4, and the resista nce of clot-bound thrombin and platelet membrane-bound factor Xa to th e heparin-antithrombin III complex. Unlike heparin, the direct thrombi n inhibitors (such as hirudin) are active against both circulating and clot-bound thrombin. However, in recent clinical trials they have not resulted in major improvements in patient outcome. Another new class of drugs, the glycoprotein IIb/IIIa receptor antagonists, blocks the f inal common pathway of platelet aggregation and is capable of preventi ng platelet accumulation at sites of injury. The net effect is a drama tic reduction in the amount of platelet membrane available to support the process of coagulation. Clinical trials with the glycoprotein IIb/ IIIa inhibitors have suggested that this class of agents may be partic ularly effective in reducing the thrombotic complications associated w ith coronary interventional procedures and may be useful in the treatm ent of acute coronary syndromes.