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Abstract & Commentary
Source: Crowther MA, et al. Oral vitamin K lowers the international normalized ratio more rapidly than subcutaneous vitamin K in the treatment of warfarin-associated coagulopathy. A randomized, controlled trial. Ann Intern Med 2002;137:251-254.
The anticoagulant effects of warfarin frequently need to be reversed for bleeding complications, excessively high international normalized ratio (INR) values, or in preparation for procedures. Although withholding warfarin is eventually effective, occasionally faster reduction in INR is necessary. Crowther and associates tested the hypothesis that oral vitamin K would reduce high INRs faster than subcutaneous vitamin K. Patients with an INR between 4.5 and 10.0 were randomized to receive 1 mg of vitamin K either orally or subcutaneously and warfarin was withheld. The primary outcome was INR on the day after vitamin K. In the 51 patients studied, the mean INR was 6. The INR had decreased to the 1.8-3.2 range the next day in 58% of the oral vitamin K group and 24% of the subcutaneous groups (odds ratio, 4.3; 95% CI, 1.1-17.4; P = .015; number needed to treat = 3). Two patients who received subcutaneous vitamin K had an increased INR the next day; this did not occur in the oral therapy group. Conversely, three patients who received oral vitamin K had INR less than 1.8, whereas none of the subcutaneous group did. Crowther et al concluded that oral vitamin K lowers high INR more rapidly than subcutaneous administration.
Commentary by Michael H. Crawford, MD
Using vitamin K to reverse a high INR prevents bleeding complications. The risk of major bleeding in patients with an INR greater than 6.0 is reported to be 4%.1 In this study, no episodes of bleeding were observed, so the incidence actually may be lower. Some have been reluctant to use vitamin K to reverse high INRs for fear of overshooting and precipitating thrombosis, such as in patients with prosthetic valves. Again, in this study no episodes of thrombosis were observed, but three patients did have INRs less than 1.8 after oral vitamin K. The results of this study suggest that in patients with a high risk of bleeding complications and no excessive risk of thrombosis, i.e., prosthetic valve, and an INR greater than 4.5, that low-dose oral vitamin K administration should be considered. Patients with high INRs and a low risk of bleeding, such as many preprocedure patients, should merely have warfarin withheld.
Dr. Crawford is Professor of Medicine, Mayo Medical School, Consultant in Cardiovascular Diseases and Director of Research, Mayo Clinic, Scottsdale, AZ.
1. Hylek EM, et al. Prospective study of the outcomes of ambulatory patients with excessive warfarin anticoagulation. Arch Intern Med 2000;160:1612-1617.