english.prescrire.org > Spotlight > Archives : 2013 > Bleeding with dabigatran, rivaroxaban, apixaban: no antidote, and little clinical experience

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Bleeding with dabigatran, rivaroxaban, apixaban: no antidote, and little clinical experience

FEATURED REVIEW Dabigatran, rivaroxaban and apixaban are oral anticoagulants used to prevent or treat thrombosis. Difficulties in the management of bleeding weigh heavily in the balance of potential harm versus potential benefit of these drugs.
Full review (5 pages) available for download by subscribers.


  • Dabigatran, rivaroxaban and apixaban are oral anticoagulants used to prevent or treat thrombosis in a variety of situations. Like all anticoagulants, these drugs can provoke bleeding.
  • How should patients be managed if bleeding occurs during dabigatran, rivaroxaban or apixaban therapy? How can the risk of bleeding be reduced in patients who require surgery or other invasive procedures? To answer these questions, we reviewed the available literature, using the standard Prescrire methodology. 
  • In clinical trials, warfarin, enoxaparin, dabigatran, rivaroxaban and apixaban were associated with a similar frequency of severe bleeding. 
  • Numerous reports of severe bleeding associated with dabigatran have been recorded since this drug was first marketed. 
  • Some situations are associated with a particularly high bleeding risk, including: even mild renal failure, advanced age, extremes in body weight and drug-drug interactions, particularly with antiplatelet agents (including aspirin), nonsteroidal anti-inflammatory drugs, and many drugs used in cardiovascular indications. 
  • In patients treated with dabigatran, rivaroxaban or apixaban, changes in the INR (international normalised ratio) and activated partial thromboplastin time (aPTT) do not correlate with the dose. In early 2013, there is still no routine coagulation test suitable for monitoring these patients; specific tests are only available in specialised laboratories. 
  • In early 2013 there is no antidote for dabigatran, rivaroxaban or apixaban, nor any specific treatment with proven efficacy for severe bleeding linked to these drugs. 
  • Recommendations on the management of bleeding in this setting are based mainly on pharmacological parameters and on scarce experimental data obtained in studies in animals or healthy volunteers.  
  • Haemodialysis reduces the plasma concentration of dabigatran, while rivaroxaban and apixaban cannot be eliminated by dialysis.
  • Prothrombin complex concentrates and recombinant activated factor VII seem to have little or no efficacy, and they carry a poorly documented risk of thrombosis.  
  • For patients undergoing surgery or other invasive procedures, clinical practice guidelines are primarily based on pharmacokinetic parameters and on extrapolation of data on vitamin K antagonists. The decision on whether or not to discontinue anticoagulation before the procedure mainly depends on the likely risk of bleeding. In patients at high risk of thrombosis, heparin can be proposed when the anticoagulant is withdrawn. 
  • In early 2013, difficulties in the management of bleeding and of situations in which there is a risk of bleeding weigh heavily in the balance of potential harm versus potential benefit of dabigatran, rivaroxaban and apixaban. When an oral anticoagulant is required, it is best to choose warfarin, a vitamin K antagonist, and the drug with which we have the most experience, except in those rare situations in which the INR cannot be maintained within the therapeutic range. 

"Bleeding with dabigatran, rivaroxaban, apixaban" Prescrire Int 2013; 22 (139): 155-159. (Pdf, subscribers only)

©Prescrire 1 June 2013

Download the full review.
Pdf, subscribers only

Dabigatran (Pradaxa°):
life-threatening bleeding
(February 2013)

Rivaroxaban (Xarelto°)
and atrial fibrillation:
continue to use warfarin or,
in some cases, dabigatran
(November 2012)