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:

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
2012 ACCP guidelines recommend prothrombin complex concentrate, human^{[5, 6]}(PCC, Kcentra) plus vitamin K1 (phytonadione) 5-10 mg IV^[2]
Minimize anaphylaxis risk of vitamin K1 by mixing in 50 mL of IV fluid and administering using an infusion pump over 20 min^[7]
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)