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

M. U. Zafar, C. Santos-Gallego, D. A. Vorchheimer, J. F. Viles-Gonzalez, S. Elmariah, C. Giannarelli, S. Sartori, D. S. Small, J. A. Jakubowski, V. Fuster, J. J. Badimon

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)100-106
Number of pages7
JournalJournal of Thrombosis and Haemostasis
Volume11
Issue number1
DOIs
StatePublished - Jan 1 2013

Keywords

  • Acute coronary syndrome
  • Antiplatelet
  • Prasugrel
  • Thienopyridine
  • Transfusion

ASJC Scopus subject areas

  • Hematology

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    Zafar, M. U., Santos-Gallego, C., Vorchheimer, D. A., Viles-Gonzalez, J. F., Elmariah, S., Giannarelli, C., Sartori, S., Small, D. S., Jakubowski, J. A., Fuster, V., & Badimon, J. J. (2013). Platelet function normalization after a prasugrel loading-dose: Time-dependent effect of platelet supplementation. Journal of Thrombosis and Haemostasis, 11(1), 100-106. https://doi.org/10.1111/jth.12058