Immature platelet fraction (IPF) determined with an automated method predicts clopidogrel hyporesponsiveness

The mechanisms for the variability in antiplatelet effects of clopidogrel are not elucidated entirely. Immature (reticulated) platelets may modulate the antiplatelet effects of clopidogrel but must be measured using flow cytometry. Whether new automated detection techniques yield similar results is not known. The objectives of the study to evaluate the role of immature platelets assessed by an automated method in response to the anti-platelet effects of clopidogrel. Twenty-nine healthy volunteers had platelet studies performed before and 1 week after 75 mg daily dosing of clopidogrel. Immature platelet fraction (IPF) was determined using an automated particle counter. Subjects were stratified into tertiles based on the IPF. Platelet studies included light transmission aggregometry (LTA), and vasodilator stimulated phosphoprotein phosphorylation (VASP-P) determined by platelet reactivity index (PRI). Baseline platelet aggregation responses to 2, 5 and 20 lM ADP, were similar in all three tertiles, however they were greater in the upper than in the lower tertile of immature platelets after clopidogrel in response to 5 lM ADP (54% vs. 23%, P = 0.02), with concordant trends for the other two concentrations. PRI was also greater in the upper tertile after clopidogrel (71.2% vs. 57.8%, P = 0.04). The frequency of clopidogrel hyporesponsiveness (aggregation[50% in response to 5 lM of ADP) was also higher in the upper tertile when compared to lower tertile, (60%) versus (10%) respectively (P = 0.0001). Immature platelets measured using an automated method, are associated with impaired response to antiplatelet effects of clopidogrel.