Article    Table of Contents                    Full Text of this article    PDF of this article (PDFs free after 6 months)    Summary for Patients    Summary for Patients (PDF)    Figures/Tables List    Related articles in Annals  Services    Send comment/rapid response letter    Notify a friend about this article    Alert me when this article is cited    Add to Personal Archive    Download to Citation Manager    ACP Search                            Get Permissions  Google Scholar    Search for Related Content  PubMed Articles in PubMed by Author:    Crowther, M. A.    Ageno, W.    Related Articles in PubMed    PubMed Citation    PubMed

BRIEF COMMUNICATION

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.

Related articles in Annals:

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

Annals 2002 137: I-39. [Full Text]  

Letters
Oral Vitamin K for Warfarin-Associated Coagulopathy
Rick Weideman AND Amit P. Patel

Annals 2003 138: 610. [Full Text]  

Letters
Oral Vitamin K for Warfarin-Associated Coagulopathy
Elin Ringstrom AND Heather Long

Annals 2003 138: 610-611. [Full Text]  

Letters
Oral Vitamin K for Warfarin-Associated Coagulopathy
Mark A. Crowther

Annals 2003 138: 611. [Full Text]  

This article has been cited by other articles:

				J. Ansell, J. Hirsh, E. Hylek, A. Jacobson, M. Crowther, and G. Palareti Pharmacology and Management of the Vitamin K Antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition) Chest, June 1, 2008; 133(6_suppl): 160S - 198S. [Abstract] [Full Text] [PDF]

				F. Dentali and M. A. Crowther Management of Excessive Anticoagulant Effect Due to Vitamin K Antagonists Hematology, January 1, 2008; 2008(1): 266 - 270. [Abstract] [Full Text] [PDF]

				B. E. Ickx and A. Steib Perioperative management of patients receiving vitamin K antagonists: [Prise en charge perioperatoire des patients traites aux antagonistes de la vitamine K] Can J Anesth, June 1, 2006; 53(6_suppl): S113 - S122. [Abstract] [Full Text] [PDF]

				K. J. DeZee, W. T. Shimeall, K. M. Douglas, N. M. Shumway, and P. G. O'Malley Treatment of Excessive Anticoagulation With Phytonadione (Vitamin K): A Meta-analysis. Arch Intern Med, February 27, 2006; 166(4): 391 - 397. [Abstract] [Full Text] [PDF]

				D. A. Garcia, S. Regan, M. Crowther, and E. M. Hylek The Risk of Hemorrhage Among Patients With Warfarin-Associated Coagulopathy J. Am. Coll. Cardiol., February 21, 2006; 47(4): 804 - 808. [Abstract] [Full Text] [PDF]

				J. N. Goldstein, S. H. Thomas, V. Frontiero, A. Joseph, C. Engel, R. Snider, E. E. Smith, S. M. Greenberg, and J. Rosand Timing of Fresh Frozen Plasma Administration and Rapid Correction of Coagulopathy in Warfarin-Related Intracerebral Hemorrhage Stroke, January 1, 2006; 37(1): 151 - 155. [Abstract] [Full Text] [PDF]

				M. A. Smythe, W. E. Dager, and N. M. Patel Managing Complications of Anticoagulant Therapy Journal of Pharmacy Practice, October 1, 2004; 17(5): 327 - 346. [Abstract] [PDF]

				J. Ansell, J. Hirsh, L. Poller, H. Bussey, A. Jacobson, and E. Hylek The Pharmacology and Management of the Vitamin K Antagonists: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy Chest, September 1, 2004; 126(3_suppl): 204S - 233S. [Abstract] [Full Text] [PDF]

				S. E. Wilson, H. G. Watson, and M. A. Crowther Low-dose oral vitamin K therapy for the management of asymptomatic patients with elevated international normalized ratios: a brief review Can. Med. Assoc. J., March 2, 2004; 170(5): 821 - 824. [Abstract] [Full Text] [PDF]

				A. Lubetsky, H. Yonath, D. Olchovsky, R. Loebstein, H. Halkin, and D. Ezra Comparison of Oral vs Intravenous Phytonadione (Vitamin K1) in Patients With Excessive Anticoagulation: A Prospective Randomized Controlled Study Arch Intern Med, November 10, 2003; 163(20): 2469 - 2473. [Abstract] [Full Text] [PDF]

				J. Hirsh, V. Fuster, J. Ansell, and J. L. Halperin American Heart Association/American College of Cardiology Foundation guide to warfarin therapy J. Am. Coll. Cardiol., May 7, 2003; 41(9): 1633 - 1652. [Full Text] [PDF]

				R. Weideman and A. P. Patel Oral Vitamin K for Warfarin-Associated Coagulopathy Ann Intern Med, April 1, 2003; 138(7): 610 - 610. [Full Text] [PDF]

				E. Ringstrom and H. Long Oral Vitamin K for Warfarin-Associated Coagulopathy Ann Intern Med, April 1, 2003; 138(7): 610 - 611. [Full Text] [PDF]

				J. Hirsh, V. Fuster, J. Ansell, and J. L. Halperin American Heart Association/American College of Cardiology Foundation Guide to Warfarin Therapy Circulation, April 1, 2003; 107(12): 1692 - 1711. [Full Text] [PDF]

				POEM: Vitamin K works faster orally than subcutaneously BMJ, February 1, 2003; 326(7383): 0 - 0. [Full Text] [PDF]

				ADDITIONAL ARTICLES ABSTRACTED IN ACP JOURNAL CLUB Evid. Based Med., January 1, 2003; 8(1): 3 - 3. [Full Text] [PDF]

				I. Malik JournalScan Heart, December 1, 2002; 88(5): 551 - 552. [Full Text]

				Oral or Subcutaneous Vitamin K for Elevated INR? Journal Watch Cardiology, September 27, 2002; 2002(927): 2 - 2. [Full Text]

				Oral vs. Subcutaneous Vitamin K for Elevated INRs Journal Watch (General), September 10, 2002; 2002(910): 2 - 2. [Full Text]