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The anticoagulant effect of protamine sulfate is attenuated in the presence of platelets or elevated factor VIII concentrations.

Publication ,  Journal Article
Bolliger, D; Szlam, F; Azran, M; Koyama, K; Levy, JH; Molinaro, RJ; Tanaka, KA
Published in: Anesth Analg
September 2010

BACKGROUND: Protamine sulfate is the antidote for heparin, but in excess it exerts weak anticoagulation. METHODS: We evaluated the effects of increasing protamine concentrations (0 to 24 microg/mL) on prothrombin time and diluted Russell's viper venom time measurements on thrombin generation in platelet-poor and platelet-rich plasma after activation by tissue factor or actin, and on thromboelastometry in platelet-poor plasma and whole blood from 6 healthy volunteers. The reversibility of excess protamine (24 microg/mL) by recombinant factor VIIa or factor VIII/von Willebrand factor concentrate was also tested. RESULTS: Protamine prolonged prothrombin time and Russell's viper venom time, concentration dependently. Protamine also increased lag time and decreased peak of thrombin generation in platelet-poor plasma after tissue factor and actin activation. In platelet-rich plasma with platelets at 50 to 200 x 10(3)/microL, protamine (24 microg/mL) prolonged the lag time, but had no effect on peak thrombin generation. The addition of factor VIII/von Willebrand factor (1.5-3.0 U/mL) to platelet-poor plasma with protamine (24 microg/mL) decreased lag time and increased peak thrombin generation with actin activation. A therapeutic concentration of recombinant factor VIIa (60 nM) only affected the lag time of thrombin generation triggered with actin. In agreement, protamine increased coagulation time evaluated by thromboelastometry significantly more in platelet-poor plasma than in whole blood. CONCLUSIONS: We demonstrated that protamine affects the propagation of thrombin generation, which is partially reversed by platelets or increased factor VIII/von Willebrand factor concentrations. The present data suggest that excess protamine might potentially increase bleeding in the case of severe thrombocytopenia or low factor VIII.

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Published In

Anesth Analg

DOI

EISSN

1526-7598

Publication Date

September 2010

Volume

111

Issue

3

Start / End Page

601 / 608

Location

United States

Related Subject Headings

  • Thrombin
  • Thrombelastography
  • Prothrombin Time
  • Protamines
  • Middle Aged
  • Male
  • Humans
  • Heparin Antagonists
  • Female
  • Factor VIII
 

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Bolliger, D., Szlam, F., Azran, M., Koyama, K., Levy, J. H., Molinaro, R. J., & Tanaka, K. A. (2010). The anticoagulant effect of protamine sulfate is attenuated in the presence of platelets or elevated factor VIII concentrations. Anesth Analg, 111(3), 601–608. https://doi.org/10.1213/ANE.0b013e3181e9ed15
Bolliger, Daniel, Fania Szlam, Marc Azran, Kaoru Koyama, Jerrold H. Levy, Ross J. Molinaro, and Kenichi A. Tanaka. “The anticoagulant effect of protamine sulfate is attenuated in the presence of platelets or elevated factor VIII concentrations.Anesth Analg 111, no. 3 (September 2010): 601–8. https://doi.org/10.1213/ANE.0b013e3181e9ed15.
Bolliger D, Szlam F, Azran M, Koyama K, Levy JH, Molinaro RJ, et al. The anticoagulant effect of protamine sulfate is attenuated in the presence of platelets or elevated factor VIII concentrations. Anesth Analg. 2010 Sep;111(3):601–8.
Bolliger, Daniel, et al. “The anticoagulant effect of protamine sulfate is attenuated in the presence of platelets or elevated factor VIII concentrations.Anesth Analg, vol. 111, no. 3, Sept. 2010, pp. 601–08. Pubmed, doi:10.1213/ANE.0b013e3181e9ed15.
Bolliger D, Szlam F, Azran M, Koyama K, Levy JH, Molinaro RJ, Tanaka KA. The anticoagulant effect of protamine sulfate is attenuated in the presence of platelets or elevated factor VIII concentrations. Anesth Analg. 2010 Sep;111(3):601–608.

Published In

Anesth Analg

DOI

EISSN

1526-7598

Publication Date

September 2010

Volume

111

Issue

3

Start / End Page

601 / 608

Location

United States

Related Subject Headings

  • Thrombin
  • Thrombelastography
  • Prothrombin Time
  • Protamines
  • Middle Aged
  • Male
  • Humans
  • Heparin Antagonists
  • Female
  • Factor VIII