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Practice Therapeutics

Urgent reversal of vitamin K antagonists

BMJ 2018; 360 doi: (Published 04 January 2018) Cite this as: BMJ 2018;360:j5424

This article has a correction. Please see:

  1. Beverley J Hunt, professor of thrombosis and haemostasis and consultant1 2 3,
  2. Marcel Levi, professor of medicine, consultant and chief executive4 5
  1. 1King's College, London, UK
  2. 2Departments of Haematology and Pathology, Guy’s & St Thomas’ NHS Foundation Trust, London
  3. 3Viapath, London
  4. 4University College London Hospitals NHS Foundation Trust, London
  5. 5Academic Medical Centre, University of Amsterdam
  1. Correspondence to: B J Hunt, Thrombosis & Haemophilia Centre, St Thomas’ Hospital, London SE1 7EH Beverley.hunt{at}

What you need to know

  • There are three options for urgent reversal of anticoagulant effects of vitamin K antagonists such as warfarin: vitamin K, prothrombinase complex concentrate, and fresh frozen plasma

  • The reversal of vitamin K antagonists can be monitored with the international normalised ratio (INR) to measure clotting time

  • Prevention of bleeding is key: the patient’s INR should be kept in the desired therapeutic range, and extra INR checks are needed during illness and when starting a new medication that may interfere with warfarin’s effect

A 78 year old man is brought to the emergency department after collapsing. He is drowsy with signs of a left hemiparesis. Computed tomography of the brain shows an intracranial bleed. He has a history of atrial fibrillation, and he has been taking warfarin (INR target 2-3) for several years. His wife says he started a course of antibiotics for a chest infection a week before. His INR is 8.

Warfarin is a vitamin K antagonist (fig 1) and a coumarin (more accurately 4-hydroxycoumarin) derivative. It is the most commonly used vitamin K antagonist in the world.1 The main uses for vitamin K antagonists are prevention of stroke in patients with atrial fibrillation, and prevention of thrombosis in those with previous venous thromboembolism or with mechanical heart valves. In some countries, other coumarins are used with a similar action but a shorter (acenocoumarol) or longer (phenprocoumon) half-life.

Fig 1

Coagulation factors II (prothrombin), VII, IX, and X, and the physiological anticoagulant proteins C and S, undergo vitamin K-dependent post-translational carboxylation in the liver before secretion into plasma. This step activates the coagulation factors, giving them the ability to bind to calcium. During carboxylation, vitamin K is oxidised to its inactive form vitamin K epoxide, which is regenerated by the enzyme vitamin K epoxide reductase. Vitamin K antagonists act as competitive …

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