Blood platelets are the primary defence mechanism involved in physiological haemostasis. Their disorders constitute a crucial risk factor in arterial thrombosis. As arterial thrombi are predominantly composed of platelet aggregates formed under conditions of elevated shear stress at sites of atherosclerotic vascular injury, prevention of arterial thrombosis can be considered the main target of antiplatelet therapy. However, a large interindividual variability in the clinical response to aspirin, clopidogrel and GpIIb/IIIa inhibitors is widely acknowledged by physicians as a barrier for rational pharmacotherapy. Several case-control studies have indicated that various polymorphisms of different platelet glycoprotein and receptors might contribute to arterial thrombosis. Moreover, polymorphisms of hepatic cytocrome P450, which generate the active metabolites of clopidogrel, are likely to play a considerable role in determining the in vivo response to this prodrug. Functional studies have revealed widespread gene-gene interactions, as well as modulation by non-genetic factors. Thus, the response to anti-platelet drugs is a classic “complex” trait, and the available data require a great deal of caution to avoid misinterpretation. In this article, we review the role of these polymorphisms in modulating platelet function and platelet response to inhibitors.
Keywords: Platelet Inhibition, Blood platelets, haemostasis, antiplatelet therapy, clopidogrel, aspirin, active metabolites, gene-gene interactions, polymorphisms
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