Platelet glycoprotein IIb/IIIa antagonists - What are the relevant issues concerning their pharmacology and clinical use?

During the last decade, intensive efforts have been made to evaluate the ro le of the platelet glycoprotein (GP) IIb/IIIa complex in platelet-mediated thrombus formation. Significant efforts have also been made to design poten t antagonists of this "final common pathway" of platelet aggregation to be used as novel therapeutic strategies to treat acute coronary syndromes. Alt hough several different GP IIb/IIIa antagonists have convincingly demonstra ted the usefulness of this platelet-directed therapeutic strategy, a number of lingering unsolved and sometimes misunderstood issues concerning the ph armacology and optimal clinical usefulness of these agents remain to be exp lored, This article reviews these issues, which include antagonist affinity , reversibility, and receptor specificity. Other issues are related to the effects of GP IIb/IIIa receptor availability, neoepitopes induced by antago nist binding with the potential to mediate thrombocytopenia, optimal method s of platelet monitoring and, perhaps ultimately, the potential therapeutic index of the oral class of GP IIb/IIIa antagonists, All of these specific issues are likely to be illuminated in the next several years, which will g reatly determine the breadth of this therapeutic class.