Testing platelet activation with a shear-dependent platelet function test versus aggregation-based tests - Relevance for monitoring long-term glycoprotein IIb/IIIa inhibition

Background-Tests developed to monitor glycoprotein (GP) IIb/IIIa blockade d o not properly reflect platelet function in vivo and need a baseline (pretr eatment) value. Because GP IIb/IIIa is essential in platelet aggregation an d thrombosis under shear conditions, a flow-dependent approach to monitor i ts inhibition can be used. Methods and Results-We compared a test based on flow-dependent platelet dep osition, the Cone and Platelet Analyzer (CPA), with in vitro platelet aggre gometry and the Rapid Platelet Function Assay (RPFA) on platelet function a fter GP IIb/IIIa inhibition. In vitro, increasing concentrations of abcixim ab (0% to 100% receptor occupancy) were tested. Ex vivo, platelet function was monitored with the CPA and with aggregometry for up to 1 week after abc iximab administration. The CPA was better correlated with the percentage of free GP IIb/IIIa receptors than was aggregometry or the RPFA. Only the RPF A, when expressed as a ratio over baseline (pretreatment), was comparable t o the CPA. Ex vivo, the CPA, but not aggregometry, showed prolonged platele t inhibition with gradual recovery from GP IIb/IIIa receptor blockade in th e first week after abciximab administration. Conclusions-Platelet function assessment by shear-induced deposition is a r eliable test to monitor a wide range of GP IIb/IIIa inhibition. Its accurac y does not require a baseline reference. The effects of GP IIb/IIIa blockad e on platelet function should be examined under high shear conditions.