The anticoagulant effect of protamine sulfate is attenuated in the presence of platelets or elevated factor VIII concentrations.
Journal Article (Journal Article)
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.
Full Text
Duke Authors
Cited Authors
- Bolliger, D; Szlam, F; Azran, M; Koyama, K; Levy, JH; Molinaro, RJ; Tanaka, KA
Published Date
- September 2010
Published In
Volume / Issue
- 111 / 3
Start / End Page
- 601 - 608
PubMed ID
- 20686004
Electronic International Standard Serial Number (EISSN)
- 1526-7598
Digital Object Identifier (DOI)
- 10.1213/ANE.0b013e3181e9ed15
Language
- eng
Conference Location
- United States