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Practice Therapeutics

Specific antidotes for bleeding associated with direct oral anticoagulants

BMJ 2017; 357 doi: (Published 25 May 2017) Cite this as: BMJ 2017;357:j2216
  1. Allison Burnett, antithrombosis stewardship pharmacist, clinical assistant professor12,
  2. Deborah Siegal, assistant professor3,
  3. Mark Crowther, chair4
  1. 1University of New Mexico Hospital, Albuquerque, New Mexico, USA
  2. 2University of New Mexico College of Pharmacy, Albuquerque, New Mexico, USA
  3. 3Department of Medicine, Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada
  4. 4Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada
  1. Correspondence to: A Burnett aburnett{at}

What you need to know

  • Direct oral anticoagulants (DOACs) are shown to be safe and effective alternatives to vitamin K antagonists in appropriately selected patients, despite a lack of specific antidotes.

  • For most bleeding events, expert opinion suggests that cessation of the DOAC and supportive care will likely be sufficient.

  • Currently, only one specific antidote, idarucizumab, is licensed for use and is indicated to reverse dabigatran in patients with life threatening haemorrhage or need for urgent surgery.

An 83 year old woman is brought to the emergency department by her care giver who noticed her altered mental status following two episodes of passing black faeces. The woman has a history of ischaemic stroke associated with atrial fibrillation and hypertension and is on dabigatran for stroke prevention. She took her last dose a few hours ago. Computed tomography of the head shows no acute intracranial abnormalities. Abdominal and rectal exams are normal. Her blood pressure is 82/56 mm Hg. The multidisciplinary team in charge of her care arrives to talk with her and her family about antidotes for reversing her anticoagulation.

Direct oral anticoagulants (DOACs) are a relatively new class of oral anticoagulants developed as alternatives to vitamin K antagonists such as warfarin, and are indicated in non-valvular atrial fibrillation and venous thromboembolism (Box 1).

Box 1: Direct oral anticoagulants (DOACs)

Commercially available DOACs include
  • the direct thrombin inhibitor dabigatran etexilate (Pradaxa)

  • the direct factor Xa inhibitors apixaban (Eliquis), edoxaban (Lixiana, Savaysa), and rivaroxaban (Xarelto).

  • DOACs have advantages over vitamin K antagonists (eg, warfarin), including

  • rapid onset and offset of action

  • fewer drug, disease state, and dietary interactions

  • fixed dosing

  • no need for routine monitoring of anticoagulant activity.1 2

Randomised controlled trials and meta-analyses among patients with non-valvular atrial fibrillation or acute venous thromboembolism have shown DOACs to be at least as effective as vitamin K antagonists in preventing or treating thromboembolic events.3 4 …

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