Ethanol enhances the inhibitory effect of an oral GPIIb/IIIa antagonist on human platelet function

Abstract Ethanol is a commonly used substance that can significantly influence platelet responses when combined with therapeutic drugs. In in vitro studies, we combined ethanol with LY309562, a novel 2,6-disubstituted isoquinolone RGD mimic that competes for fibrinogen binding to GPIIb/IIIa. Ethanol inhibits aggregation and secretion, partly by inhibiting thromboxane A 2 formation. We measured aggregation and secretion of dense granule contents by platelets labeled with [ 14 C] serotonin in plasma from blood anticoagulated with FPRCH 2 Cl (PPACK). Alone, LY309562 dose-dependently inhibited aggregation induced by 10 μmol/L adenosine diphosphate, 1 μg/mL collagen, 2 μmol/L U46619 (a thromboxane A 2 mimetic), or 15 μmol/L SFLLRN (protease-activated receptor-1-activating peptide); inhibition was complete at 1 μmol/L LY309562 and partial at 0.1 μmol/L (50% inhibitory concentration [IC 50 ] 0.19-0.33 μmol/L). Secretion induced by collagen, U46619, and SFLLRN was also inhibited by LY309562 (IC 50 0.08-0.31 μmol/L). At inhibitory concentrations of LY309562, ethanol (2 or 4 mg/mL) further inhibited responses to collagen, U46619, and SFLLRN (IC 50 for aggregation 0.12-0.16 μmol/L; for secretion 0.04-0.12 μmol/L). Responses of aspirin-treated platelets to U46619 were also inhibited, indicating that ethanol was not acting solely by inhibiting thromboxane A 2 formation. Because it is likely that our results with LY309562 are representative of results with other GPIIb/IIIa antagonists, our in vitro data suggest that the concomitant use of GPIIb/IIIa antagonists and consumption of alcoholic beverages may result in further impairment of platelet participation in hemostasis and thrombosis. (J Lab Clin Med 2002;140:391-7)