Warfarin Overanticoagulation 

Updated: Aug 19, 2015
  • Author: Abimbola Farinde, PharmD, PhD; more...
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Warfarin Overanticoagulation

Below are recommendations for managing elevated international normalized ratios (INRs) or bleeding in patients receiving vitamin K antagonists (eg, warfarin).

Supratherapeutic INR but INR <4.5, no bleeding or need for rapid reversal:

  • Lower the dose according to the recommendations below or omit a dose, monitor daily, and resume at an adjusted lower dose when the target INR is reached .

INR 4.5-10, no bleeding:

  • Omit 1-2 doses, monitor INR, and readjust dose
  • 2012 ACCP guidelines suggest against routine use of vitamin K1 ( phytonadione) [1]
  • 2008 ACCP guidelines suggest considering vitamin K1 (phytonadione) 1-2.5 mg PO once [2]
  • Other recommendation: Vitamin K1 (phytonadione) 1 mg PO or 0.5 mg IV [3]
  • INR should be reduced within 24 hours

INR >10.0, no bleeding:

  • Hold warfarin, monitor INR, and readjust dose
  • 2012 ACCP guidelines recommend vitamin K1 PO (dose not specified) [1]
  • 2008 ACCP guidelines suggest administering vitamin K1 (phytonadione) 2.5-5 mg PO once; if INR reduction observed within 24-48 h, monitor INR and give additional vitamin K if needed [2]
  • Other recommendation: Vitamin K1 (phytonadione) 2-2.5 mg PO or 0.5-1 mg IV [3]

Minor bleeding, any elevated INR:

  • Hold warfarin, monitor INR, and readjust dose
  • Consider vitamin K1 (phytonadione) 2.5-5 mg PO once; may repeat if needed after 24 h [3]

Major bleeding, any elevated INR:

  • Hold warfarin, monitor INR, and readjust dose
  • 2012 ACCP guidelines recommend prothrombin complex concentrate, human (PCC, Kcentra) plus vitamin K1 (phytonadione) 5-10 mg IV [1]
  • Minimize anaphylaxis risk of vitamin K1 by mixing in 50 mL of IV fluid and administering using an infusion pump over 20 min [4]
  • May also consider supplementation with fresh frozen plasma (FFP) or factor VIIa, recombinant (rVIIa, NovoSeven)
  • Note: High vitamin K doses (ie, ≥10 mg) may cause warfarin resistance for a week or more; consider using heparin, low-molecular-weight heparin, or direct thrombin inhibitors to provide adequate thrombosis prophylaxis in clinical conditions that require chronic anticoagulation therapy (eg, atrial fibrillation)

Life-threatening bleeding and elevated INR:

  • Hold warfarin therapy and give FFP  WITH vitamin K 10 mg by slow IV infusion, repeated, if necessary depending on the INR.

Additional resources

Warfarin and Superwarfarin Toxicity

Bleeding Risk Index for Warfarin Therapy