Heparinase I (neutralase) reversal of systemic anticoagulation

Abstract

Background: Protamine causes multiple adverse reactions. Heparinase I, a specific enzyme that inactivates heparin, is a possible alternative to protamine. In this study, the authors examined the efficacy of heparinase I to reverse heparin-induced anticoagulation in vitro and compared heparinase I to protamine as an antagonist of heparin-induced anticoagulation in dogs. Methods: In the in vitro study, blood was obtained from the extracorporeal circuits of 12 patients, and activated clotting times were determined after adding different concentrations of heparinase I. In the in vitro study, 24 anesthetized dogs received 300 units/kg heparin injected intravenously for 5 s, then 10 min later, 3.9 mg/kg protamine, 5-41 μg/kg heparinase I, or the vehicle (n - 4/group) were administered intravenously, and activated clotting times and hemodynamics were measured. Results: In the in vitro study, heparin concentrations of 3.3 ± l.0 (mean ± SD) units/ml (~0.033 mg/ml; n < 12) were reversed in the blood of patients by heparinase I at concentrations >0.490 μg/ml. In the canine study, heparinase at all doses studied and protamine effectively reversed the anticoagulating effects of heparin within 10 min of administration. Protamine produced adverse hemodynamic effects, whereas heparinase or its vehicle produced no significant change in arterial pressure. Conclusion: Both heparinase I and protamine effectively reversed heparin anticoagulation. However, as opposed to protamine, heparinase I did not produce any significant hemodynamic changes when given as a bolus to dogs.