Lack of usefulness of prolonged bleeding times in predicting hemorrhagic events in patients receiving the 7E3 glycoprotein IIb/IIIa platelet antibody

Abstract

Hemorrhagic events remain the most worrisome complication in patients receiving drugs that after hemostasis for treatment of acute coronary syndromes. The 7E3 Fab monoclonal antibody provides a dose-dependent inhibition of platelet aggregation via the glycoprotein IIb/IIIa receptor. This study examines the correlation of hemostatic parameters with bleeding events in patients receiving intravenous 7E3 while enrolled in acute myocardial infarction and high-risk percutaneous transluminal coronary angioplasty pilot studies. Patients with acute myocardial infarction received 100 mg of tissue-type plasminogen activator over 3 hours followed by an escalating intravenous bolus dose of murine 7E3 (0.1 mg/kg [n = 5], 0.2 mg/kg [n = 22], 0.15 mg/kg [n = 13], 0.25 mg/kg [n = 20]). Patients in the high-risk angioplasty trial received a chimeric 7E3 bolus (up to 0.25 mg/kg) with (n = 32) or without (n = 15) intravenous continuous infusion of 7E3 (10 μg/min for 6 to 24 hours) after elective angioplasty. Patients in both studies received aspirin therapy (325 mg/day) and partial thromboplastin time-guided (1.5 to 2 times normal) heparin infusion. Bleeding events occurred in 34 of 124 patients (27%). The median template bleeding times (minutes) for patients in the groups with bleeding versus no bleeding events in the trials was 13.5 versus 14 and 30 versus 30, respectively (p = NS). In patients with myocardial infarction, a substantial decline in platelet count at 24 hours was associated with bleeding (p = 0.02). These findings suggest, in contrast to a previous report, that the template bleeding time is an imprecise index for predicting hemorrhagic events in patients receiving platelet fibrinogen receptor inhibitor, with or without thrombolytic therapy, and raises questions about the use of this hemostatic parameter in future clinical trials.