Abstract
Aspirin has stood the test of time over decades as the gold standard for relatively effective, safe, and inexpensive antiplatelet therapy. However, aspirin is only modestly effective in preventing arterial thrombosis in certain settings, and it is virtually ineffective in others (for example, preventing coronary restenosis after angioplasty). These observations have been the impetus for the development of more effective antiplatelet strategies, the rational basis of which is largely our understanding of normal platelet function. The most clinically effective platelet inhibitors yet developed produce broad inhibition of platelet function by blockade of the final common pathway of aggregation, in which fibrinogen binds to its platelet membrane receptor localized in the glycoprotein (Gp) IIb/ IIIa complex. The Gp IIb/IIIa complex is a member of the family of integrins, which are cell membrane receptors for adhesive proteins. The binding of fibrinogen to platelet Gp IIb/IIIa occurs via a specific amino acid sequence, arginine-glycine-aspartic acid. Effective antagonists of platelet Gp IIb/IIIa function have included monoclonal antibodies against Gp IIb/IIIa, peptide (peptidomimetic) antagonists of Gp IIb/IIIa, and nonpeptide (nonpeptide mimetic) antagonists of Gp IIb/IIIa. The major risk of any antiplatelet strategy is the potential for bleeding complications, since currently we do not understand the molecular distinction between protective hemostasis and pathologic thrombosis.
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