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Review
. 2011 Dec;7(4):281-7.
doi: 10.1007/s13181-011-0178-y.

Dabigatran: review of pharmacology and management of bleeding complications of this novel oral anticoagulant

Michael Ganetsky  1 , Kavita M Babu, Steven D Salhanick, Robert S Brown, Edward W Boyer
Affiliations
Review

Dabigatran: review of pharmacology and management of bleeding complications of this novel oral anticoagulant

Michael Ganetsky et al. J Med Toxicol. 2011 Dec.

Abstract

Dabigatran (Pradaxa) is a competitive direct thrombin inhibitor approved by the US FDA for prevention of embolic stroke in patients with nonvalvular atrial fibrillation. Dabigatran has a pharmacokinetic profile that produces predictable anticoagulation responses, does not undergo CYP 450 metabolism, has few drug-drug and drug-food interactions, and does not require frequent laboratory monitoring of clotting parameters. Clinicians are rapidly prescribing this agent as a replacement for warfarin therapy. However, no therapeutic agent has been accepted to reliably reverse the hemorrhagic complications of dabigatran. As of yet, there is no solid evidence to guide management of bleeding complications; management should start with local control of bleeding when possible and transfusion of pRBCs if needed. Transfusion of FFP would not be expected to help control bleeding. Limited and mixed data exist for transfusion of factor VIIa and prothrombin complex concentrates; these therapies should be considered as well as dialysis, which will increase elimination in patients with life-threatening or closed-space bleeding due to dabigatran. We present an article that reviews the pharmacokinetics, clinical trial literature, and consensus guidelines regarding this novel oral anticoagulant.

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Figures

Fig. 1
Fig. 1
Simplified diagram of the coagulation cascade demonstrating pharmacology of dabigatran
Fig. 2
Fig. 2
Thrombin enables thrombus formation by activating multiple coagulation factors, catalyzing the conversion of fibrinogen to fibrin, and causing platelet aggregation. Dabigatran binds at the active site, thus inhibiting both free and fibrin-bound thrombin. Heparin exerts its action by increasing the affinity of antithrombin for thrombin. Heparin can only inhibit free thrombin since fibrin-bound thrombin has both exosites occupied and is relatively protected from the effects of antithrombin
See this image and copyright information in PMC

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