Warfarin Overanticoagulation
Below are recommendations for managing elevated international normalized ratios (INRs) or bleeding in patients receiving vitamin K antagonists (eg, warfarin). [1]
Supratherapeutic INR but INR < 4.5, no bleeding or need for rapid reversal:
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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:
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Omit 1-2 doses, monitor INR, and readjust dose
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2012 ACCP guidelines suggest against routine use of vitamin K1 (phytonadione) [2]
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2008 ACCP guidelines suggest considering vitamin K1 (phytonadione) 1-2.5 mg PO once [3]
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Other recommendation: Vitamin K1 (phytonadione) 1 mg PO or 0.5 mg IV [4]
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INR should be reduced within 24 hours
INR >10.0, no bleeding:
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Hold warfarin, monitor INR, and readjust dose
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2012 ACCP guidelines recommend vitamin K1 PO (dose not specified) [2]
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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]
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Other recommendation: Vitamin K1 (phytonadione) 2-2.5 mg PO or 0.5-1 mg IV [4]
Minor bleeding, any elevated INR:
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Hold warfarin, monitor INR, and readjust dose
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Consider vitamin K1 (phytonadione) 2.5-5 mg PO once; may repeat if needed after 24 h [4]
Major bleeding, any elevated INR:
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Hold warfarin, monitor INR, and readjust dose
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2012 ACCP guidelines recommend prothrombin complex concentrate, human [5, 6] (PCC, Kcentra) plus vitamin K1 (phytonadione) 5-10 mg IV [2]
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Minimize anaphylaxis risk of vitamin K1 by mixing in 50 mL of IV fluid and administering using an infusion pump over 20 min [7]
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May also consider supplementation with fresh frozen plasma (FFP) or factor VIIa, recombinant (rVIIa, NovoSeven)
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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:
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Hold warfarin therapy and give FFP WITH vitamin K 10 mg by slow IV infusion, repeated, if necessary depending on the INR.
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