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Optimizing antiplatelet therapy in patients with acute coronary syndromes: a role for monitoring platelet reactivity.

Platelet activation is seminal in the thrombosis underlying acute coronary syndromes. Furthermore, high levels of platelet reactivity are associated with an increased risk of future cardiovascular events both in apparently healthy subjects and men with overt coronary artery disease. We have developed a sensitive and specific assay of platelet reactivity using minimally altered whole blood to assess activation of glycoprotein IIb/IIIa and expression of P-selectin (a measure of alpha granule degranulation). This assay reliably identifies subjects with increased platelet reactivity who may benefit from more aggressive inhibition of platelet function on a long-term basis. In addition, this assay is sensitive to the effects of antiplatelet agents such as glycoprotein IIb/IIIa inhibitors. Abciximab, tirofiban and eptifibatide all inhibit fibrinogen binding in a concentration of dependent manner. However, marked variation in the extent of inhibition was seen between individuals. We have postulated that greater inhibition of agonist-induced fibrinogen binding in some and limited inhibition in others may account, in part, for tendencies to bleeding and recurrent thrombosis. This type of assay should allow for determination of platelet reactivity and titration of dosage to the needs of each individual. The assay has the potential to improve the care of patients with acute coronary syndromes and of those undergoing percutaneous coronary intervention as well as assist in the design of clinical trials utilizing antiplatelet drugs.