TY - JOUR
T1 - Inhibition of platelet aggregation with a glycoprotein IIb-IIIa antagonist does not prevent thrombin generation in patients undergoing thrombolysis for acute myocardial infarction
AU - Kleiman, Neal S.
AU - Tracy, Russell P.
AU - Talley, J. David
AU - Sigmon, Kristina
AU - Joseph, Diane
AU - Topol, Eric J.
AU - Califf, Robert M.
AU - Kitt, Michael
AU - Ohman, E. Magnus
N1 - Funding Information:
This work was supported by a grant from COR Therapeutics, Inc., South San Francisco, CA.
Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 2000
Y1 - 2000
N2 - Thrombin activity has been implicated as a mechanism for failed reperfusion and reocclusion following thrombolysis. Aggregating platelets provide a phospholipid surface on which prothrombin is cleaved to form thrombin. We examined markers of thrombin generation and activity in patients enrolled in a randomized, placebo-controlled, dose escalating trial of the platelet glycoprotein IIb-IIIa inhibitor eptifibatide (Integrilin(TM)) administered concomitantly with tissue plasminogen activator for the treatment of myocardial infarction. Measurements were obtained at baseline, at 90 minutes, and at 6, 12, and 24 hours after starting therapy. Eptifibatide inhibited platelet aggregation in response to 20 μM ADP. Levels of fibrinopeptide A (FPA), thrombin-antithrombin complexes (TAT), and prothrombin fragment 1.2 (F1.2) were not lower in patients treated with eptifibatide than in the control group. In the course of dose escalation, two groups of patients received the same 135 μg/kg bolus of eptifibatide, one with and one without a heparin bolus. FPA levels were dramatically lower in the heparin-treated patients. Levels of FPA, TAT, and F1.2 were not higher in patients with than in those without recurrent ischemia, or in patients without than in those with Thrombolysis in Myocardial Infarction (TIMI) grade 3 angiographic flow at 90 minutes. These data suggest that thrombin generation and activity persist following thrombolysis, despite inhibition of platelet aggregation, and that treatment with inhibitors of thrombin activity may be required even when glycoprotein IIb-IIIa inhibitors are used.
AB - Thrombin activity has been implicated as a mechanism for failed reperfusion and reocclusion following thrombolysis. Aggregating platelets provide a phospholipid surface on which prothrombin is cleaved to form thrombin. We examined markers of thrombin generation and activity in patients enrolled in a randomized, placebo-controlled, dose escalating trial of the platelet glycoprotein IIb-IIIa inhibitor eptifibatide (Integrilin(TM)) administered concomitantly with tissue plasminogen activator for the treatment of myocardial infarction. Measurements were obtained at baseline, at 90 minutes, and at 6, 12, and 24 hours after starting therapy. Eptifibatide inhibited platelet aggregation in response to 20 μM ADP. Levels of fibrinopeptide A (FPA), thrombin-antithrombin complexes (TAT), and prothrombin fragment 1.2 (F1.2) were not lower in patients treated with eptifibatide than in the control group. In the course of dose escalation, two groups of patients received the same 135 μg/kg bolus of eptifibatide, one with and one without a heparin bolus. FPA levels were dramatically lower in the heparin-treated patients. Levels of FPA, TAT, and F1.2 were not higher in patients with than in those without recurrent ischemia, or in patients without than in those with Thrombolysis in Myocardial Infarction (TIMI) grade 3 angiographic flow at 90 minutes. These data suggest that thrombin generation and activity persist following thrombolysis, despite inhibition of platelet aggregation, and that treatment with inhibitors of thrombin activity may be required even when glycoprotein IIb-IIIa inhibitors are used.
KW - Eptifibatide
KW - Glycoprotein IIb-IIIa
KW - Myocardial infarction
KW - Thrombolysis
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U2 - 10.1023/A:1018650123272
DO - 10.1023/A:1018650123272
M3 - Article
C2 - 10590183
AN - SCOPUS:0033980788
VL - 9
SP - 5
EP - 12
JO - Journal of Thrombosis and Thrombolysis
JF - Journal of Thrombosis and Thrombolysis
SN - 0929-5305
IS - 1
ER -