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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

Mark A. Crowther, MD, MSc; James D. Douketis, MD; Terri Schnurr, RN; Luigi Steidl, MD; Valentina Mera, MD; Carolina Ultori, MD; Achille Venco, MD; and Walter Ageno, MD
[+] Article, Author, and Disclosure Information

From St. Joseph's Hospital, Hamilton, Ontario, Canada; and Ospedale di Circolo, Varese, Italy.

Grant Support: Dr. Crowther holds a Research Scholarship from the Canadian Institutes for Health Research. Dr. Douketis holds a Research Scholarship from the Heart and Stroke Foundation of Canada.

Requests for Single Reprints: Mark A. Crowther, MD, MSc, St. Joseph's Hospital, Room L208, 50 Charlton Avenue East, Hamilton, Ontario L8N 4A6, Canada; e-mail, crowthrm@mcmaster.ca.

Potential Conflicts of Interest: None disclosed.

Current Author Addresses: Drs. Crowther and Douketis and Ms. Schnurr: St. Joseph's Hospital, 50 Charlton Avenue East, Hamilton, Ontario L8N 4A6, Canada.

Drs. Steidl, Mera, Ultori, Venco, and Ageno: Ospedale di Circolo, Medicina Interna, Viale Borri 57, 21100 Varese, Italy.

Author Contributions: Conception and design: M.A. Crowther, J.D. Douketis, T. Schnurr.

Analysis and interpretation of the data: M.A. Crowther, L. Steidl, V. Mera, C. Ultori, A. Venco, W. Ageno.

Drafting of the article: M.A. Crowther, J.D. Douketis.

Critical revision of the article for important intellectual content: M.A. Crowther, J.D. Douketis, L. Steidl, V. Mera, C. Ultori, A. Venco, W. Ageno.

Final approval of the article: M.A. Crowther, J.D. Douketis, V. Mera, C. Ultori, A. Venco, W. Ageno.

Provision of study materials or patients: M.A. Crowther, J.D. Douketis, T. Schnurr, L. Steidl, V. Mera, C. Ultori, A. Venco, W. Ageno.

Statistical expertise: M.A. Crowther.

Administrative, technical, or logistic support: M.A. Crowther, T. Schnurr.

Collection and assembly of data: M.A. Crowther, J.D. Douketis, T. Schnurr, L. Steidl, V. Mera, C. Ultori, A. Venco, W. Ageno.

Ann Intern Med. 2002;137(4):251-254. doi:10.7326/0003-4819-137-4-200208200-00009
Text Size: A A A

Background: Excessive anticoagulation due to warfarin use is associated with hemorrhage. Subcutaneously administered vitamin K has not been evaluated for the treatment of warfarin-associated coagulopathy, yet it is widely used.

Objective: To show that oral vitamin K is more effective than subcutaneous vitamin K in the treatment of warfarin-associated coagulopathy.

Design: Randomized, controlled trial.

Setting: Two teaching hospitals.

Patients: Patients with an international normalized ratio (INR) between 4.5 and 10.0.

Intervention: Warfarin therapy was withheld, and 1 mg of vitamin K was given orally or subcutaneously.

Measurements: The primary outcome measure was the INR on the day after administration of vitamin K. Secondary outcome measures were hemorrhage and thrombosis during a 1-month follow-up period.

Results: 15 of 26 patients receiving oral vitamin K and 6 of 25 patients receiving subcutaneous vitamin K had therapeutic INRs on the day after study drug administration (P = 0.015; odds ratio, 4.32 [95% CI, 1.13 to 17.44]).

Conclusion: Oral vitamin K lowers INR more rapidly than subcutaneous vitamin K in asymptomatic patients who have supratherapeutic INR values while receiving warfarin.


Grahic Jump Location
Appendix Figure. INR = international normalized ratio.
Flow of patients through the study.
Grahic Jump Location
Grahic Jump Location
International normalized ratio (INR) of patients receiving oral (left) and subcutaneous (right) vitamin K.

More patients who received oral vitamin K than those who received subcutaneous vitamin K had INR values in the range of 1.8 to 3.2. In addition, 1 mg of oral vitamin K lowers the INR more rapidly than does subcutaneous vitamin K.

Grahic Jump Location




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Summary for Patients

Vitamin K Reverses Overanticoagulation with Warfarin More Quickly When Given by Mouth Than by Injection

The summary below is from the full report titled “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.” It is in the 20 August 2002 issue of Annals of Internal Medicine (volume 137, pages 251-254). The authors are MA Crowther, JD Douketis, T Schnurr, L Steidl, V Mera, C Ultori, A Venco, and W Ageno.


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