Differential Effects of Glycoprotein IIb/IIIa Antagonists on Platelet Microaggregate and Macroaggregate Formation and Effect of Anticoagulant on Antagonist Potency: Implications for Assay Methodology and Comparison of Different Antagonists

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Abstract

Background

Citrated platelet-rich plasma (PRP) turbidimetry is used for assessing pharmacodynamic effects of glycoprotein (GP) IIb/IIIa antagonists in clinical trials. However, citrate can enhance the potency of at least eptifibatide (Integrilin), and turbidimetry is insensitive to microaggregate formation. We compared PRP turbidimetry, as a measure of macroaggregate formation, with single-platelet counting in both whole blood and PRP as a measure of microaggregate formation, using both citrate and hirudin anticoagulation.

Conclusions

GP IIb/IIIa antagonist potency is variably enhanced by citrate. Macroaggregation is inhibited more effectively than microaggregation, most markedly in the case of eptifibatide in hirudinized blood. These observations have implications for the interpretation and comparison of pharmacodynamic assays and possibly for the risk/benefit ratio of different agents. (Circulation. 1998;98:1616-1621.)

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