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Vitamin K to Correct Overanticoagulation
- Mark A. Crowther, MD, MSc; and
- David Garcia, MD
- From McMaster University, Hamilton, Ontario L8N 4A6, Canada, and University of New Mexico, Albuquerque, NM 87131.
IN RESPONSE:
Our study found that low-dose oral vitamin K does not reduce bleeding in asymptomatic patients who present with INR values between 4.5 and 10.0. Thus, one should not recommend vitamin K to patients similar to those we enrolled if the intent is to reduce bleeding.
The INR decreased more rapidly in patients who received vitamin K, consistent with the pattern we have observed in previous studies. This INR decrease confirms that the formulation used in our study was effective (1). Similarly, we decided only after extensive discussion that we would not mandate how warfarin was given after study drug administration. We agree with Drs. Swaim and Macik that patients whose INR decreased quickly (whether they received vitamin K or placebo) probably had less-dramatic reductions of warfarin dose. Such warfarin dose adjustment is not only appropriate but also reflects routine clinical practice. Thus, our study represents the best estimate of the efficacy (or lack thereof) of vitamin K in the “real world.”
We acknowledge that INR (and the coagulant potential of the blood) could change between the time of measurement and the administration of study drug several hours later. However, this delay had no effect on the observation that the rate of major hemorrhage at 7 days among the patients who received placebo was low—a finding consistent with other studies (2, 3). Furthermore, it reflects how vitamin K is given in the real world, where most patients have INR measured in a community laboratory, are found to have an elevated INR, and are called to make arrangements for vitamin K administration hours later.
Larger doses of vitamin K may have produced larger INR corrections and thus may have reduced bleeding; however, overcorrection of the INR with an attendant risk for thrombosis would then be a consideration. Our choice of dose was based on our previous articles and on the fact that the 1.25-mg dose was one quarter of a standard-sized vitamin K tablet available in the United States. However, we cannot rule out the possibility that larger doses (or other formulations) of vitamin K might have reduced bleeding or increased thrombosis.
We welcome Dr. Pengo and colleagues' comments, because he and his research group have done much of the seminal work in this area (4). However, the observational data he presents in his letter lack a comparator group; therefore, conclusions about relative efficacy cannot be drawn.
Article and Author Information
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Potential Financial Conflicts of Interest: Consultancies: M.A. Crowther (Anton Pharmaceuticals).
