Journal of Thrombosis and Thrombolysis

, Volume 35, Issue 2, pp 295-301

First online:

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

  • Brian DaleAffiliated withSchool of Pharmacy and Medical Sciences, University of South Australia
  • , John W. EikelboomAffiliated withDepartment of Medicine, McMaster UniversityThrombosis and Atherosclerosis Research InstitutePopulation Health Research Institute Email author 
  • , Jeffrey I. WeitzAffiliated withDepartment of Medicine, McMaster UniversityThrombosis and Atherosclerosis Research Institute
  • , Ed YoungAffiliated withThrombosis and Atherosclerosis Research Institute
  • , Jeremy S. PaikinAffiliated withDepartment of Medicine, McMaster University
  • , Michiel CoppensAffiliated withPopulation Health Research Institute
  • , Richard P. WhitlockAffiliated withDepartment of Surgery, McMaster University
  • , Stuart J. ConnollyAffiliated withDepartment of Medicine, McMaster University
  • , Jeffrey S. GinsbergAffiliated withDepartment of Medicine, McMaster University
    • , Jack HirshAffiliated withDepartment of Medicine, McMaster UniversityPopulation Health Research Institute

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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.


Dabigatran Warfarin Thrombin generation