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Warfarin reversal


High INR from warfarin can occur for many reasons. The reason for an elevated INR needs to be investigated and addressed. High INR with no bleeding can often be managed in the community or in the short stay unit of the emergency department given appropriate risk assessment. Initial management of an elevated INR in the ED depends on:

  • Laboratory INR result
    • <4.5
    • 4.5-10
    • >10
  • Severity of any active bleeding
  • Assessment of bleeding risk
  • Need for invasive or surgical procedures
  • Hypotension not responding to resuscitation
  • A reduction in Hb ≥ 20 g/L and/or transfusion of ≥ 2 units of red cells

Phytomenadione or vitamin K1 (Konakion) can be given to reverse the anticoagulant effect of warfarin. It is used for patients with high INRs (without bleeding) or those with active bleeding. Intravenous vitamin K1 achieves a more rapid response compared with oral administration, with an onset of action of around 6 to 8 hours; however, both routes have a similar effect on INR by 24 hours. Where there is life-threatening (critical organ) or clinically significant bleeding, higher IV doses of vitamin K1 (5 to 10 mg) are used. The anticoagulant effect of warfarin can be difficult to re-establish after the administration of large doses of vitamin K1.

For immediate reversal, prothrombin complex concentrates (PCC) are preferred over fresh frozen plasma (FFP). Prothrombinex-VF is the only PCC routinely used for warfarin reversal in Australia. It contains factors II, IX, X and low levels of factor VII. FFP is not routinely needed in combination with Prothrombinex-VF. FFP can be used when Prothrombinex-VF is unavailable. Vitamin K1 is essential for sustaining the reversal achieved by PCC or FFP.

Surgery can be conducted with minimal increased risk of bleeding if INR ≤ 1.5. For minor procedures where bleeding risk is low, warfarin may not need to be interrupted. If necessary, warfarin can be withheld for 5 days before surgery, or intravenous vitamin K1 can be given the night before surgery. Perioperative management of anticoagulant therapy requires an evaluation of the risk of thrombosis if warfarin is temporarily stopped, relative to the risk of bleeding if it is continued or modified.

This should guide the management, resuscitation, referral (e.g. surgical/OT) and INR reversal strategy (drugs, doses, speed of reversal).

Further References and Resources

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