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 infarction.

BACKGROUND

The role of heparin therapy during coronary thrombolysis with streptokinase is controversial, in part because the efficacy of different conjunctive heparin regimens in inhibiting early increases of thrombin activity is not known.

METHODS

Twenty-eight patients treated with 1.5 million U of streptokinase and 165 mg of aspirin for acute myocardial infarction were randomly assigned to receive fixed 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 intravenous heparin (5,000-U bolus followed by 1,000-U/h infusion [n = 14]). Anticoagulation was assessed with serial measurements of activated partial thromboplastin time, and thrombin activity by measuring fibrinopeptide A and thrombin-antithrombin III complex levels. Plasma concentrations 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 subcutaneous heparin versus 43%, 76% and 86% of those given intravenous heparin at 1, 2 and 3 h, respectively (p = 0.6). Concentrations of fibrinopeptide 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 vs. fixed dose intravenous heparin 11.8 +/- 5.2 nmol/liter) at 48 h (p = 0.4). No significant changes in the concentration of thrombin-antithrombin III complexes were found between the two groups.

CONCLUSIONS

Fixed dose intravenous heparin attenuates increases in fibrinopeptide A early after streptokinase. Subsequent fixed dose intravenous and subcutaneous heparin have similar effects but are relatively ineffective in suppressing thrombin activity, suggesting a role for more potent antithrombin agents during coronary thrombolysis with streptokinase.