Platelet Glycoprotein IIb/IIIa Antagonists

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Abstract
Abstract —During the last decade, intensive efforts have been made to evaluate the role of the platelet glycoprotein (GP) IIb/IIIa complex in platelet-mediated thrombus formation. Significant efforts have also been made to design potent antagonists of this “final common pathway” of platelet aggregation to be used as novel therapeutic strategies to treat acute coronary syndromes. Although several different GP IIb/IIIa antagonists have convincingly demonstrated the usefulness of this platelet-directed therapeutic strategy, a number of lingering unsolved and sometimes misunderstood issues concerning the pharmacology and optimal clinical usefulness of these agents remain to be explored. 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 antagonist binding with the potential to mediate thrombocytopenia, optimal methods 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 greatly determine the breadth of this therapeutic class.

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