Antagonism of warfarin-induced hypoprothrombinemia with use of low-dose subcutaneous vitamin K-1

Historically, oral or intravenous doses of vitamin K-1 for supratherapeutic anticoagulation have ranged from 10 mg to 50 mg. Intravenous administration of vitamin K-1 carries a rare but serious risk. No data specifically confirm the use of low-dose subcutaneous vitamin K-1 for warfarin induced hypoprothrombinemia. The aim of this study was twofold: 1) to test the general utility of recommendations put forth by the Third Conference of Antithrombotic Therapy, and 2) to test the reliability of the subcutaneous route for this treatment. Six patients with excessive international normalized ratios (INRs) and no intervention were compared with 12 patients with excessive INRs who were given low doses of subcutaneous vitamin K-1. The rate of decline of the INR to 3 was statistically significantly greater in favor of the treatment group. The amount of time required to achieve an INR of 3 differed between the two groups by almost 2 complete day (23 hours) in favor of the treatment group. The average dose of subcutaneous vitamin K-1 required to return a patient to an INR of 3 or less was 4.9 mg. A few participants required an additional dose of the same magnitude or less to return to an INR within the therapeutic range. This study provides sufficient evidence that subcutaneous vitamin K-1 is an effective alternative to intravenous administration of vitamin K-1 for warfarin-induced hypoprothrombinemia and permits administration in accordance with the current published recommendations for intravenous vitamin K-1 administration in this scenario.