Thrombin generation assay and viscoelastic coagulation monitors demonstrate differences in the mode of thrombin inhibition between unfractionated heparin and bivalirudin.


Journal Article

BACKGROUND: Coagulation tests, such as activated partial thromboplastin time and activated clotting time, are used to monitor the effects of unfractionated heparin and the direct thrombin inhibitor, bivalirudin. These tests reflect only the initial phase of blood clotting, when <5% of thrombin has been formed. In this study, we sought to determine if similar increases in activated partial thromboplastin time or activated clotting time due to heparin or bivalirudin would reflect the same degree of inhibition of thrombin formation. METHODS: Thrombin formation was evaluated in platelet-poor plasma activated in the presence of heparin (0-5 U/mL) or bivalirudin (0-30 microg/mL) using a thrombin generation assay (Thrombinoscope). Prothrombin activation was measured by prothrombin fragment 1.2 (F1.2) formation. Thrombus formation was further evaluated in kaolin-activated whole blood samples containing heparin (1.5 or 2.5 U/mL) or bivalirudin (12.5 or 25 microg/mL) using Sonoclot and thromboelastography. RESULTS: Based on the Thrombinoscope results, increasing concentrations of bivalirudin and heparin progressively delayed the onset of thrombin formation, but only heparin dose-dependently decreased the amount of thrombin generated. Heparin and bivalirudin delayed the onset of F1.2 formation, but there was no difference in peak F1.2 levels between bivalirudin and non-anticoagulated samples (206 +/- 28.2 vs 182 +/- 23.9 nmol/L, P = 0.09). In heparinized samples, F1.2 levels were significantly lower (75.7 +/- 29.8 nmol/L, P < 0.05) than controls. Heparin and bivalirudin prolonged the onset of clotting on viscoelastic monitors, but only heparin decreased the rate of thrombus formation. CONCLUSION: Thrombus formation kinetics differs between heparin and bivalirudin despite similar prolongation of clotting test values.

Full Text

Duke Authors

Cited Authors

  • Tanaka, KA; Szlam, F; Sun, HY; Taketomi, T; Levy, JH

Published Date

  • October 2007

Published In

Volume / Issue

  • 105 / 4

Start / End Page

  • 933 - 939

PubMed ID

  • 17898368

Pubmed Central ID

  • 17898368

Electronic International Standard Serial Number (EISSN)

  • 1526-7598

Digital Object Identifier (DOI)

  • 10.1213/01.ane.0000278868.23814.3b


  • eng

Conference Location

  • United States