Warfarin Overanticoagulation: Warfarin Overanticoagulation

Below are recommendations for managing elevated international normalized ratios (INRs) or bleeding in patients receiving vitamin K antagonists (eg, warfarin). ^{[1, 9]}

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) ^[2]

• 2008 ACCP guidelines suggest considering vitamin K1 (phytonadione) 1-2.5 mg PO once ^[3]

• Other recommendation: Vitamin K1 (phytonadione) 1 mg PO or 0.5 mg IV ^[4]

• 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) ^[2]

• 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 ^[3]

• Other recommendation: Vitamin K1 (phytonadione) 2-2.5 mg PO or 0.5-1 mg IV ^[4]

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 ^[4]

Major bleeding, any elevated INR:

• Hold warfarin, monitor INR, and readjust dose

• Minimize anaphylaxis risk of vitamin K1 by mixing in 50 mL of IV fluid and administering using an infusion pump over 20 min ^[7]

• 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

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.