HEPARINASE-I (NEUTRALASE) REVERSAL OF SYSTEMIC ANTICOAGULATION

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 hep arinase I to reverse hepatin-induced anticoagulation in vitro and comp ared heparinase I to protamine as an antagonist of heparin-induced ant icoagulation in dogs. Methods In the in vitro study, blood was obtaine d from the extracorporeal circuits of 12 patients, and activated clott ing times were determined after adding different concentrations of hep arinase I. In the in vivo study, 24 anesthetized dogs received 300 uni ts/kg heparin injected intravenously for 5 s, then 10 min later, 3.9 m g/kg protamine, 5-41 mu g/kg heparinase I, or the vehicle (n = 4/group ) were administered intravenously, and activated clotting times and he modynamics were measured. Results in the in vitro study, heparin conce ntrations of 3.3 +/- 1.0 (mean +/- SD) units/ml (similar to 0.033 mg/m l; n = 12) were reversed in the blood of patients by heparinase I at c oncentrations > 0.490 mu g/ml. In the canine study, heparinase at all doses studied and protamine effectively reversed the anticoagulating e ffects of heparin within 10 min of administration. Protamine produced adverse hemodynamic effects, whereas heparinase or its vehicle produce d no significant change in arterial pressure. Conclusion: Both heparin ase I and protamine effectively reversed heparin anticoagulation. Howe ver, as opposed to protamine, heparinase I did not produce any signifi cant hemodynamic changes when given as a bolus to dogs.