Vitamin K does not reduce bleeding after excessive warfarin

Crowther MA, Ageno W, Garcia D, et al. Oral Vitamin K Versus Placebo to Correct Excessive Anticoagulation in Patients Receiving Warfarin: A Randomized Trial. Ann Intern Med 2009 Mar 3;150(5):293-300.

http://www.annals.org/cgi/content/abstract/150/5/293
http://www.annals.org/cgi/content/full/150/5/293
http://www.annals.org/cgi/reprint/150/5/293

Vitamin K rapidly reversed the effects of warfarin. However, there were no differences between groups in the number of participants with bleeding events, clots, or other complications.

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Related:
Summaries for Patients
Is Vitamin K Helpful for People Who Have Taken Too Much Warfarin?
Annals 2009 150: I-25.
http://www.annals.org/cgi/content/full/150/5/I-25
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Oral Vitamin K Versus Placebo to Correct Excessive Anticoagulation in Patients Receiving Warfarin
A Randomized Trial

Mark A. Crowther, MD, MSc; Walter Ageno, MD; David Garcia, MD; Luqi Wang, PhD; Dan M. Witt, PharmD; Nathan P. Clark, PharmD; Mark D. Blostein, MD; Susan R. Kahn, MD, MSc; Sara K. Vesely, PhD; Sam Schulman, MD; Michael J. Kovacs, MD; Marc A. Rodger, MD, MSc; Phillip Wells, MD, MSc; David Anderson, MD, MSc; Jeffery Ginsberg, MD; Rita Selby, MD, MSc; Sergio Siragusa, MD; Mauro Silingardi, MD; Mary Beth Dowd, PharmD; and Clive Kearon, MD, PhD

3 March 2009 | Volume 150 Issue 5 | Pages 293-300

Background: Low-dose oral vitamin K decreases the international normalized ratio (INR) in overanticoagulated patients who receive warfarin therapy. Its effects on bleeding events are uncertain.
Objective: To see whether low-dose oral vitamin K reduces bleeding events over 90 days in patients with warfarin-associated coagulopathy.
Design: Multicenter, randomized, placebo-controlled trial. Randomization was computer-generated, and participants were allocated to trial groups by using sequentially numbered study drug containers. Patients, caregivers, and those who assessed outcomes were blinded to treatment assignment.
Setting: 14 anticoagulant therapy clinics in Canada, the United States, and Italy.
Patients: Nonbleeding patients with INR values of 4.5 to 10.0.
Intervention: Oral vitamin K, 1.25 mg (355 patients randomly assigned; 347 analyzed), or matching placebo (369 patients randomly assigned; 365 analyzed).
Measurements: Bleeding events (primary outcome), thromboembolism, and death (secondary outcomes).
Results: 56 patients (15.8%) in the vitamin K group and 60 patients (16.3%) in the placebo group had at least 1 bleeding complication (absolute difference, –0.5 percentage point [95% CI, –6.1 to 5.1 percentage points]); major bleeding events occurred in 9 patients (2.5%) in the vitamin K group and 4 patients (1.1%) in the placebo group (absolute difference, 1.5 percentage points [CI, –0.8 to 3.7 percentage points]). Thromboembolism occurred in 4 patients (1.1%) in the vitamin K group and 3 patients (0.8%) in the placebo group (absolute difference, 0.3 percentage point [CI, –1.4 to 2.0 percentage points]). Other adverse effects were not assessed. The day after treatment, the INR had decreased by a mean of 1.4 in the placebo group and 2.8 in the vitamin K group (P  Limitation: Patients who were actively bleeding were not included, and warfarin dosing after enrollment was not mandated or followed.
Conclusion: Low-dose oral vitamin K did not reduce bleeding in warfarin recipients with INRs of 4.5 to 10.0.
Funding: Canadian Institutes of Health Research and Italian Ministry of Universities and Research.

Editors' Notes

Context

• Vitamin K decreases the international normalized ratio (INR) in overanticoagulated patients who receive warfarin therapy, but its effect on clinical outcomes is less clear.
Contribution

• Trial investigators detected no differences in the frequency of bleeding, thromboembolism, or death among overanticoagulated patients who received warfarin therapy and were randomly assigned to receive low-dose vitamin K or placebo.
Caution

• The study was underpowered to detect differences in major bleeding.
Implication

• Low-dose vitamin K corrects the INR in overanticoagulated patients who received warfarin therapy, but it has little effect on clinical outcomes. Withdrawal of warfarin may be all that is necessary to manage elevated INRs.

—The Editors

Copyright © 2009 by the American College of Physicians.