Platelet function normalization after a prasugrel loading-dose

Time-dependent effect of platelet supplementation

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

Research output: Contribution to journalArticle

33 Citations (Scopus)

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

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Blood Platelets
Platelet Transfusion
Acute Coronary Syndrome
Prasugrel Hydrochloride
Hemostatics
Platelet Count
Platelet Aggregation
Adenosine Diphosphate
Healthy Volunteers
Tissue Donors

Keywords

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

ASJC Scopus subject areas

  • Hematology

Cite this

Zafar, M. U., Santos-Gallego, C., Vorchheimer, D. A., Viles Gonzalez, J., Elmariah, S., Giannarelli, C., ... 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

Platelet function normalization after a prasugrel loading-dose : Time-dependent effect of platelet supplementation. / Zafar, M. U.; Santos-Gallego, C.; Vorchheimer, D. A.; Viles Gonzalez, Juan; Elmariah, S.; Giannarelli, C.; Sartori, S.; Small, D. S.; Jakubowski, J. A.; Fuster, V.; Badimon, J. J.

In: Journal of Thrombosis and Haemostasis, Vol. 11, No. 1, 01.01.2013, p. 100-106.

Research output: Contribution to journalArticle

Zafar, MU, Santos-Gallego, C, Vorchheimer, DA, Viles Gonzalez, J, Elmariah, S, Giannarelli, C, Sartori, S, Small, DS, Jakubowski, JA, Fuster, V & Badimon, JJ 2013, 'Platelet function normalization after a prasugrel loading-dose: Time-dependent effect of platelet supplementation', Journal of Thrombosis and Haemostasis, vol. 11, no. 1, pp. 100-106. https://doi.org/10.1111/jth.12058
Zafar MU, Santos-Gallego C, Vorchheimer DA, Viles Gonzalez J, Elmariah S, Giannarelli C et al. Platelet function normalization after a prasugrel loading-dose: Time-dependent effect of platelet supplementation. Journal of Thrombosis and Haemostasis. 2013 Jan 1;11(1):100-106. https://doi.org/10.1111/jth.12058
Zafar, M. U. ; Santos-Gallego, C. ; Vorchheimer, D. A. ; Viles Gonzalez, Juan ; Elmariah, S. ; Giannarelli, C. ; Sartori, S. ; Small, D. S. ; Jakubowski, J. A. ; Fuster, V. ; Badimon, J. J. / Platelet function normalization after a prasugrel loading-dose : Time-dependent effect of platelet supplementation. In: Journal of Thrombosis and Haemostasis. 2013 ; Vol. 11, No. 1. pp. 100-106.
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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{\circledR} 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{\circledR} 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.",
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AU - Viles Gonzalez, Juan

AU - Elmariah, S.

AU - Giannarelli, C.

AU - Sartori, S.

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