Heparinase I (neutralase) reversal of systemic anticoagulation
Heparinase I (neutralase) reversal of systemic anticoagulation
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DOI：
10.1097/00000542-199608000-00016
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发表时间：
1996-08-01
期刊：
影响因子：
8.8
通讯作者：
Szlam, F
中科院分区：
文献类型：
--
作者：
Michelsen, LG;Kikura, M;Szlam, F
背景：鱼精蛋白可引起多种不良反应。肝素酶I是一种使肝素失活的特殊酶，是鱼精蛋白的一种可能的替代品。方法体外实验中，12例犬体外循环取血，加入不同浓度的肝素酶I后，测定激活凝血时间。在体内实验中，24只麻醉犬静脉注射肝素300U/kg，连续5次，给S 5次，10min后，分别静脉注射鱼精蛋白3.9 mg/kg、鱼精蛋白5~41mU/kg或赋形剂(n=4)。结果在体外实验中，肝素浓度为3.3+/-1.0(平均值+/-SD)单位/ml(与0.033 mg/ml相似；在犬的研究中，所有剂量的肝素酶和鱼精蛋白在给药10分钟内都能有效地逆转肝素的抗凝作用。鱼精蛋白对血流动力学有不良影响，而肝素酶或其载体对动脉压无明显影响。结论：肝素酶I和鱼精蛋白均能有效逆转肝素抗凝作用。然而，与鱼精蛋白相反，肝素酶I在给狗推注时没有产生任何显著的血流动力学变化。
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 hepatin-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 vivo 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 mu g/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 +/- 1.0 (mean +/- SD) units/ml (similar to 0.033 mg/ml; n = 12) were reversed in the blood of patients by heparinase I at concentrations > 0.490 mu g/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.