Platelet function normalization after a prasugrel loading-dose: Time-dependent effect of platelet supplementation

Background:Hemostatic benefits of platelet transfusions in thienopyridine-treated acute coronary syndrome (ACS) patients may be compromised by residual metabolite in circulation.Objectives:To estimate the earliest time after a prasugrel loading-dose when added platelets are no longer inhibited by prasugrel's active metabolite.Methods:Baseline platelet reactivity of healthy subjects (n=25, 30±5years, 68% male) on ASA 325mg was tested using maximum platelet aggregation (MPA, ADP 20μm) and VerifyNow^® P2Y12 and was followed by a 60mg prasugrel loading-dose. At 2, 6, 12 and 24h post-dose, fresh concentrated platelets from untreated donors were added ex-vivo to subjects' blood, raising platelet counts by 0% (control), 40%, 60% and 80%. To estimate the earliest time when prasugrel's active metabolite's inhibitory effect on the added platelets ceases, platelet function in supplemented samples was compared across time-points to identify the time when effect of supplementation on platelet function stabilized (i.e. the increase in platelet reactivity was statistically similar to that at the next time-point).Results:Supplemented samples showed concentration-dependent increases in platelet reactivity vs. respective controls by both MPA and VerifyNow^® at all assessment time-points. For each supplementation level, platelet reactivity showed a sharp increase from 2 to 6h but was stable (P=NS) between 6 and 12h.Conclusions:The earliest measured time when supplemented platelets were not inhibited by circulating active metabolite of prasugrel was 6h after a prasugrel loading-dose. These findings may have important implications for prasugrel-treated ACS patients requiring platelet transfusions during surgery.