THROMBIN GENERATION, INHIBITION AND CLINICAL OUTCOMES IN PATIENTS WITH ACUTE MYOCARDIAL-INFARCTION TREATED WITH THROMBOLYTIC THERAPY AND HEPARIN - RESULTS FROM THE GUSTO-I TRIAL

Objectives. We sought to assess the effects of antithrombotic therapy after thrombolysis for acute myocardial infarction on markers of throm bin generation and activity and to determine the relation of these mar kers with clinical outcomes. Background. Thrombin activation and gener ation often occur with thrombolysis for acute myocardial infarction. A ntithrombotic regimens have been developed to reduce the resulting thr ombotic complications. Methods. We sampled plasma markers of thrombin generation and activity after thrombolysis in 292 patients. We assesse d the relations of these markers with clinical outcomes at 30 days. Re sults. Fibrinopeptide A (FPA), a marker of thrombin activity toward fi brinogen, was elevated at baseline (12.3 ng/ml) and increased to 18.4 ng/ml by 90 min after streptokinase and subcutaneous heparin treatment , With intravenous heparin, this increase was attenuated, but intraven ous heparin did not prevent thrombin generation, as measured by prothr ombin fragment 1.2 (F1.2). Heparin level, measured by anti-Xa activity , correlated with activated partial thromboplastin time (aPTT, r = 0.6 2 to 0.67), Thrombin activity, measured by FPA, was as closely related to aPTT as to the heparin level. Baseline levels of F1.2 were signifi cantly related to the risk of death or reinfarction at 30 days (p = 0. 008); values 12 h after enrollment also were related to 30-day mortali ty (p = 0.05). Conclusions. Although intravenous heparin partly suppre sses the increased thrombin activity associated with thrombolysis, it does not inhibit thrombin generation. The aPTT mas as good a measure o f suppression of thrombin activity as the heparin level itself. Hemato logic markers of thrombin generation were found to be related to the s ubsequent risk of thrombotic events. (C) 1998 by the American College of Cardiology.