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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

20 August 2002 | Volume 137 Issue 4 | Pages 251-254

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.

Editors' Notes Context Giving vitamin K when stopping warfarin increases the rate at which the international normalized ratio (INR) returns to normal. Although many clinicians give vitamin K subcutaneously, it appears that oral vitamin K reduces INR more rapidly. Contribution This randomized, controlled trial compared oral with subcutaneous vitamin K for patients receiving warfarin who had an INR of 4.5 to 10.0 but no bleeding. Oral administration normalized the INR faster than the subcutaneous route. Clinical Implications Clinicians should consider oral administration when prescribing vitamin K for patients who become overanticoagulated while receiving warfarin. This study had limited power to evaluate bleeding or thrombotic episodes and did not include a group that simply discontinued warfarin. –The Editors

 

Author and Article 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{at}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.

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