Heparinase I (neutralase) reversal of systemic anticoagulation

Luis G. Michelsen, Mutsuhito Kikura, Jerrold H. Levy, Mi Kyoung Lee, King C. Lee, Joseph J. Zimmermann, Fania Szlam

Research output: Contribution to journalArticle

31 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)339-346
Number of pages8
JournalAnesthesiology
Volume85
Issue number2
DOIs
Publication statusPublished - 1996 Jan 1
Externally publishedYes

Fingerprint

Heparin Lyase
Protamines
Heparin
Hemodynamics
Dogs
Heparin Antagonists
Canidae
Arterial Pressure

Keywords

  • Blood, anticoagulation: heparin; heparin neutralization
  • Pharmacology: heparinase; protamine

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Cite this

Michelsen, L. G., Kikura, M., Levy, J. H., Lee, M. K., Lee, K. C., Zimmermann, J. J., & Szlam, F. (1996). Heparinase I (neutralase) reversal of systemic anticoagulation. Anesthesiology, 85(2), 339-346. https://doi.org/10.1097/00000542-199608000-00016

Heparinase I (neutralase) reversal of systemic anticoagulation. / Michelsen, Luis G.; Kikura, Mutsuhito; Levy, Jerrold H.; Lee, Mi Kyoung; Lee, King C.; Zimmermann, Joseph J.; Szlam, Fania.

In: Anesthesiology, Vol. 85, No. 2, 01.01.1996, p. 339-346.

Research output: Contribution to journalArticle

Michelsen, LG, Kikura, M, Levy, JH, Lee, MK, Lee, KC, Zimmermann, JJ & Szlam, F 1996, 'Heparinase I (neutralase) reversal of systemic anticoagulation', Anesthesiology, vol. 85, no. 2, pp. 339-346. https://doi.org/10.1097/00000542-199608000-00016
Michelsen LG, Kikura M, Levy JH, Lee MK, Lee KC, Zimmermann JJ et al. Heparinase I (neutralase) reversal of systemic anticoagulation. Anesthesiology. 1996 Jan 1;85(2):339-346. https://doi.org/10.1097/00000542-199608000-00016
Michelsen, Luis G. ; Kikura, Mutsuhito ; Levy, Jerrold H. ; Lee, Mi Kyoung ; Lee, King C. ; Zimmermann, Joseph J. ; Szlam, Fania. / Heparinase I (neutralase) reversal of systemic anticoagulation. In: Anesthesiology. 1996 ; Vol. 85, No. 2. pp. 339-346.
@article{d4e80c0671564be4b3b4a5f05fd717a0,
title = "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.",
keywords = "Blood, anticoagulation: heparin; heparin neutralization, Pharmacology: heparinase; protamine",
author = "Michelsen, {Luis G.} and Mutsuhito Kikura and Levy, {Jerrold H.} and Lee, {Mi Kyoung} and Lee, {King C.} and Zimmermann, {Joseph J.} and Fania Szlam",
year = "1996",
month = "1",
day = "1",
doi = "10.1097/00000542-199608000-00016",
language = "English",
volume = "85",
pages = "339--346",
journal = "Anesthesiology",
issn = "0003-3022",
publisher = "Lippincott Williams and Wilkins",
number = "2",

}

TY - JOUR

T1 - Heparinase I (neutralase) reversal of systemic anticoagulation

AU - Michelsen, Luis G.

AU - Kikura, Mutsuhito

AU - Levy, Jerrold H.

AU - Lee, Mi Kyoung

AU - Lee, King C.

AU - Zimmermann, Joseph J.

AU - Szlam, Fania

PY - 1996/1/1

Y1 - 1996/1/1

N2 - 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.

AB - 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.

KW - Blood, anticoagulation: heparin; heparin neutralization

KW - Pharmacology: heparinase; protamine

UR - http://www.scopus.com/inward/record.url?scp=0029811173&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029811173&partnerID=8YFLogxK

U2 - 10.1097/00000542-199608000-00016

DO - 10.1097/00000542-199608000-00016

M3 - Article

VL - 85

SP - 339

EP - 346

JO - Anesthesiology

JF - Anesthesiology

SN - 0003-3022

IS - 2

ER -