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 language | English |
|---|---|
| Pages (from-to) | 100-106 |
| Number of pages | 7 |
| Journal | Journal of Thrombosis and Haemostasis |
| Volume | 11 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 1 2013 |
| Externally published | Yes |
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Keywords
- Acute coronary syndrome
- Antiplatelet
- Prasugrel
- Thienopyridine
- Transfusion
ASJC Scopus subject areas
- Hematology
Cite this
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 journal › Article
}
TY - JOUR
T1 - Platelet function normalization after a prasugrel loading-dose
T2 - Time-dependent effect of platelet supplementation
AU - Zafar, M. U.
AU - Santos-Gallego, C.
AU - Vorchheimer, D. A.
AU - Viles Gonzalez, Juan
AU - Elmariah, S.
AU - Giannarelli, C.
AU - Sartori, S.
AU - Small, D. S.
AU - Jakubowski, J. A.
AU - Fuster, V.
AU - Badimon, J. J.
PY - 2013/1/1
Y1 - 2013/1/1
N2 - 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.
AB - 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.
KW - Acute coronary syndrome
KW - Antiplatelet
KW - Prasugrel
KW - Thienopyridine
KW - Transfusion
UR - http://www.scopus.com/inward/record.url?scp=84873034413&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84873034413&partnerID=8YFLogxK
U2 - 10.1111/jth.12058
DO - 10.1111/jth.12058
M3 - Article
VL - 11
SP - 100
EP - 106
JO - Journal of Thrombosis and Haemostasis
JF - Journal of Thrombosis and Haemostasis
SN - 1538-7933
IS - 1
ER -