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Dabigatran attenuates thrombin generation to a lesser extent than warfarin: could this explain their differential effects on intracranial hemorrhage and myocardial infarction?

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Abstract

Compared with warfarin, dabigatran is associated with less intracranial hemorrhage, but an increased risk of myocardial infarction. To explore these phenomena, we compared their effects on thrombin generation. Thrombin generation in plasma from 10 patients taking therapeutic doses of warfarin (mean INR 2.6) was compared with that in plasma containing 250 ng/mL dabigatran. Although lag times were similar when thrombin generation was induced by recalcification or with a range of tissue factor concentrations, there was a greater reduction in peak thrombin generation and endogenous thrombin potential in plasma from warfarin-treated patients than in dabigatran-containing plasma. Similar results were obtained when thrombin generation was determined in plasma samples from 18 warfarin or 36 dabigatran treated patients entered into the RE-LY trial. Warfarin suppresses thrombin generation more efficiently than dabigatran. Greater suppression of normal hemostatic mechanisms in the brain and pathological thrombosis at sites of atherosclerotic plaque disruption may explain the higher rate of intracranial bleeding and lower rate of myocardial infarction with warfarin compared with dabigatran.

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Acknowledgments

The RE-LY trial was funded by Boehringer-Ingelheim. JWE was a member of the RE-LY Steering Committee and SJC was the Principal Investigator of the RE-LY trial. No other disclosures.

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Authors and Affiliations

  1. School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA, Australia

    Brian Dale

  2. Department of Medicine, McMaster University, Hamilton, ON, Canada

    John W. Eikelboom, Jeffrey I. Weitz, Jeremy S. Paikin, Stuart J. Connolly, Jeffrey S. Ginsberg & Jack Hirsh

  3. Department of Surgery, McMaster University, Hamilton, ON, Canada

    Richard P. Whitlock

  4. Thrombosis and Atherosclerosis Research Institute, Hamilton, ON, Canada

    John W. Eikelboom, Jeffrey I. Weitz & Ed Young

  5. Population Health Research Institute, Hamilton, ON, Canada

    John W. Eikelboom, Michiel Coppens & Jack Hirsh

  6. 237 Barton Street East, Hamilton, ON, L8L 2X2, Canada

    John W. Eikelboom

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  1. Brian Dale
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  2. John W. Eikelboom
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  3. Jeffrey I. Weitz
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  8. Stuart J. Connolly
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  9. Jeffrey S. Ginsberg
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Correspondence to John W. Eikelboom.

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Dale, B., Eikelboom, J.W., Weitz, J.I. et al. Dabigatran attenuates thrombin generation to a lesser extent than warfarin: could this explain their differential effects on intracranial hemorrhage and myocardial infarction?. J Thromb Thrombolysis 35, 295–301 (2013). https://doi.org/10.1007/s11239-012-0857-9

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  • DOI: https://doi.org/10.1007/s11239-012-0857-9

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