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

  1. Mark A. Crowther, MD, MSc;
  2. James D. Douketis, MD;
  3. Terri Schnurr, RN;
  4. Luigi Steidl, MD;
  5. Valentina Mera, MD;
  6. Carolina Ultori, MD;
  7. Achille Venco, MD; and
  8. Walter Ageno, MD
  1. From St. Joseph's Hospital, Hamilton, Ontario, Canada; and Ospedale di Circolo, Varese, Italy.

    Abstract

    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.

    Article and Author Information

    • 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.

    Summary for Patients

    • Summaries for Patients:Vitamin K Reverses Overanticoagulation with Warfarin More Quickly When Given by Mouth Than by Injection Ann Intern Med August 20, 2002 137:I-39
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    1. Ann Intern Med August 20, 2002 vol. 137 no. 4 251-254
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