FAILURE OF FIXED-DOSE INTRAVENOUS HEPARIN TO SUPPRESS INCREASES IN THROMBIN ACTIVITY AFTER CORONARY THROMBOLYSIS WITH STREPTOKINASE

Objectives. This study was designed to define the extent of inhibition of thrombin activity achieved with conjunctive fixed dose intravenous sodium heparin compared with fixed dose subcutaneous calcium heparin in patients receiving intravenous streptokinase for acute myocardial i nfarction. Background. The role of heparin therapy during coronary thr ombolysis with streptokinase is controversial, in part because the eff icacy of different conjunctive heparin regimens in inhibiting early in creases of thrombin activity is not known. Methods. Twenty eight patie nts treated with 1.5 million U of streptokinase and 165 mg of aspirin for acute myocardial infarction were randomly assigned to receive fixe d dose subcutaneous heparin therapy (12,500 U every 12 h delayed until 4 h after the end of streptokinase therapy [n = 14]) or fixed dose in travenous heparin (5,000-U bolus followed by 1,000-U/h infusion [n = 1 4]) Anticoagulation was assessed with serial measurements of activated partial thromboplastin time, and thrombin activity by measuring fibri nopeptide A and thrombin-antithrombin III complex levels. Plasma conce ntrations of creatine kinase (CK) MM isoforms were measured for 3 h to determine recanalization (increase in activity >0.18%/min). Results. Recanalization occurred in 27%, 64% and 79% of patients given subcutan eous heparin versus 43%, 76% and 86% of those given intravenous hepari n at 1, 2 and 3 h, respectively (p = 0.6). Concentrations of fibrinope ptide A (mean +/- SEM) at 1 h were higher in patients without (n = 5) than in those with (n = 23) CK-MM isoform criteria for recanalization (76.4 +/- 25.7 vs. 25.2 +/- 5.2 nmol/liter, p = 0.02), and at 1, 2 and 3 h were significantly lower with fixed dose intravenous heparin (18. 4 +/- 4.8 vs. 46.7 +/- 10.2 nmol/liter at 1 h, p = 0.004) than without heparin. After fixed dose subcutaneous heparin at 4 h, fibrinopeptide A levels were similar in both groups despite lower activated partial thromboplastin times in patients who received fixed dose subcutaneous heparin. However, fibrinopeptide A was not consistently suppressed in either group (fixed dose subcutaneous heparin 8.7 +/- 1.8 nmol/liter v s. fixed dose intravenous heparin 11.8 +/- 5.2 nmol/liter) at 48 h (p = 0.4). No significant changes in the concentration of thrombin-antith rombin In complexes were found between the two groups. Conclusions. Fi xed dose intravenous heparin attenuates increases in fibrinopeptide A early after streptokinase. Subsequent fixed dose intravenous and subcu taneous heparin have similar effects but are relatively ineffective in suppressing thrombin activity, suggesting a role for more potent anti thrombin agents during coronary thrombolysis with streptokinase.