Differential effects of citrate versus PPACK anticoagulation on measured platelet inhibition by abciximab, eptifibatide and tirofiban

Background: High levels of glycoprotein (GP) IIb/IIIa receptor inhibition a re required to prevent arterial thrombosis following percutaneous coronary intervention. Ex-vivo turbidometric platelet aggregation in citrate anticoa gulated blood samples has been the primary method previously utilized to de rive dose regimens for administering platelet GP IIb/IIIa inhibitors. Enhan ced GP IIb/IIIa binding and inhibition of platelet aggregation for eptifiba tide secondary to citrate induced reduction of ionized plasma calcium conce ntrations has been reported. Methods/Results: We evaluated the differential effects of citrate versus PP ACK anticoagulation on turbidometric platelet inhibition in normal voluntee rs by eptifibatide, tirofiban or abciximab. The decrease in ionized calcium afforded by citrate was associated with enhanced in vitro platelet inhibit ion for all three GP IIb/IIIa inhibitors, including abciximab. The magnitud e of citrate effect was greatest for eptifibatide. Both tirofiban and abcix imab have similar citrate calcium chelation associated enhancement of measu red platelet inhibition. Conclusion: Accurate assessment and comparison of platelet inhibition by GP IIb/IIIa inhibitors may require avoidance of calcium chelating anticoagula nts.