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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?
MedLine Citation:
PMID:  23242974     Owner:  NLM     Status:  Publisher    
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.
Brian Dale; John W Eikelboom; Jeffrey I Weitz; Ed Young; Jeremy S Paikin; Michiel Coppens; Richard P Whitlock; Stuart J Connolly; Jeffrey S Ginsberg; Jack Hirsh
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-12-16
Journal Detail:
Title:  Journal of thrombosis and thrombolysis     Volume:  -     ISSN:  1573-742X     ISO Abbreviation:  J. Thromb. Thrombolysis     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-17     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9502018     Medline TA:  J Thromb Thrombolysis     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA, Australia.
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