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; Clive Kearon, MD, PhD
Grant Support: By the Canadian Institutes of Health Research and the Italian Ministry of Universities.
Potential Financial Conflicts of Interest:Employment: L. Wang (McMaster University). Consultancies: M.A. Crowther (Anton Pharmaceuticals).
Reproducible Research Statement:Study protocol: Available from http://www.clinicaltrials.gov. Statistical code and data set: Available from Dr. Crowther (e-mail, email@example.com) after approval by the steering committee.
Requests for Single Reprints: Mark A. Crowther, MD, MSc, Division of Hematology and Thromboembolism, McMaster University Faculty of Health Sciences, Room L208, St. Joseph's Hospital, 50 Charlton Avenue East, Hamilton, Ontario L8N 4A6, Canada; e-mail, firstname.lastname@example.org.
Current Author Addresses: Dr. Crowther: Division of Hematology and Thromboembolism, McMaster University Faculty of Health Sciences, Room L208, St. Joseph's Hospital, 50 Charlton Avenue East, Hamilton, Ontario L8N 4A6, Canada.
Dr. Ageno: Department of Internal Medicine, Universita Degli Studi Dell'Insubria-Varese, Via Speroni 5, Varese, Italy 21100.
Dr. Garcia: University of New Mexico, 5th Ambulatory Care Center, 2211 Lomas Boulevard NE, Albuquerque, NM 87131.
Dr. Wang: St. Joseph's Healthcare, 50 Charlton Avenue East, Hamilton, Ontario L8S 2G9, Canada.
Drs. Witt, Clark, and Dowd: Kaiser Permanente Colorado Region, 280 Exempla Circle, Lafayette, CO 80026.
Dr. Blostein: McGill University, 3755 Côte Sainte-Catherine, Montreal, Quebec M3T 1E2, Canada.
Dr. Kahn: Jewish General Hospital 3755 Côte Sainte-Catherine, A-127, Montreal, Quebec H3T 1E2, Canada.
Dr. Vesely: The University of Oklahoma, Health Sciences Centre, P.O. Box 26901, Oklahoma City, OK 73126-0901.
Dr. Schulman: McMaster University, Hamilton General Hospital, 237 Barton Street East, Hamilton, Ontario L8L 2X2, Canada.
Dr. Kovacs: Hematology Division, London Health Sciences Centre, 800 Commissioners Road East, London, Ontario N6A 4G5, Canada.
Dr. Rodger: The Ottawa Hospital, 1812, Ebox 201, 501 Smyth Road, Ottawa, Ontario K1H 8L6, Canada.
Dr. Wells: The Ottawa Hospital, Civic Site, Suite F649, 1053 Carling Avenue, Ottawa, Ontario K1Y 4E9, Canada.
Dr. Anderson: Dalhousie University, Halifax, Nova Scotia B3H 3J5, Canada.
Dr. Ginsberg: McMaster University, 1200 Main Street West, HSC 3X28, Hamilton, Ontario L8N 3Z5, Canada.
Dr. Selby: Sunnybrook Health Sciences Centre, Room 0675a, 2075 Bayview Avenue, Toronto, Ontario M4N 3M5, Canada.
Dr. Siragusa: Cattedra ed U.O. di Ematologia con trapianto, Azienda Ospedaliera Universitaria Policlinico P. Giaccone, via del Vespro 127, I-90127 Palermo, Italy.
Dr. Silingardi: Arcispedale S. Maria Nuova, Azienda Ospedaliera, Viale Risorgimento 80, 42100 Reggio Emilia, Italy.
Dr. Kearon: McMaster University, Henderson General Hospital, 711 Concession Street, 40 Wing, Ground Floor, Room 115, Hamilton, Ontario L8V 1C3, Canada.
Author Contributions: Conception and design: M.A. Crowther, W. Ageno, D. Garcia, S. Schulman, P. Wells, J. Ginsberg, R. Selby, C. Kearon.
Analysis and interpretation of the data: M.A. Crowther, W. Ageno, L. Wang, D.M. Witt, N.P. Clark, S.K. Vesely, S. Schulman, M.A. Rodger, D. Anderson.
Drafting of the article: M.A. Crowther, W. Ageno, D.M. Witt, N.P. Clark, P. Wells, D. Anderson.
Critical revision of the article for important intellectual content: M.A. Crowther, W. Ageno, D. Garcia, D.M. Witt, N.P. Clark, S.R. Kahn, S. Schulman, M.J. Kovacs, M.A. Rodger, P. Wells, D. Anderson, J. Ginsberg, R. Selby, S. Siragusa, C. Kearon.
Final approval of the article: M.A. Crowther, W. Ageno, D. Garcia, M.D. Blostein, S.R. Kahn, S. Schulman, M.J. Kovacs, P. Wells, D. Anderson, J. Ginsberg, R. Selby, S. Siragusa, C. Kearon.
Provision of study materials or patients: M.A. Crowther, W. Ageno, D. Garcia, D.M. Witt, N.P. Clark, M.D. Blostein, S.R. Kahn, S. Schulman, M.J. Kovacs, P. Wells, D. Anderson, J. Ginsberg, R. Selby, M. Silingardi, M.B. Dowd, C. Kearon.
Statistical expertise: M.A. Crowther, L. Wang, S.K. Vesely, M.A. Rodger.
Obtaining of funding: M.A. Crowther, W. Ageno, M.J. Kovacs, M.A. Rodger, P. Wells, R. Selby.
Administrative, technical, or logistic support: M.A. Crowther, D. Garcia, S.R. Kahn, M.B. Dowd.
Collection and assembly of data: M.A. Crowther, L. Wang, D.M. Witt, N.P. Clark, S. Siragusa, M.B. Dowd.
ClinicalTrials.gov registration number: NCT00143715.
Crowther MA, Ageno W, Garcia D, Wang L, Witt DM, Clark NP, et al. Oral Vitamin K Versus Placebo to Correct Excessive Anticoagulation in Patients Receiving Warfarin: A Randomized Trial. Ann Intern Med. 2009;150:293-300. doi: 10.7326/0003-4819-150-5-200903030-00005
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Published: Ann Intern Med. 2009;150(5):293-300.
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.
To see whether low-dose oral vitamin K reduces bleeding events over 90 days in patients with warfarin-associated coagulopathy.
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.
14 anticoagulant therapy clinics in Canada, the United States, and Italy.
Nonbleeding patients with INR values of 4.5 to 10.0.
Oral vitamin K, 1.25 mg (355 patients randomly assigned; 347 analyzed), or matching placebo (369 patients randomly assigned; 365 analyzed).
Bleeding events (primary outcome), thromboembolism, and death (secondary outcomes).
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, âˆ’0.5 percentage point [95% CI, âˆ’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, âˆ’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, âˆ’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 (PÂ < 0.001).
Patients who were actively bleeding were not included, and warfarin dosing after enrollment was not mandated or followed.
Low-dose oral vitamin K did not reduce bleeding in warfarin recipients with INRs of 4.5 to 10.0.
Canadian Institutes of Health Research and Italian Ministry of Universities and Research.
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Hematology/Oncology, Hospital Medicine, Coagulopathies, Prevention/Screening.
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