Subscribe to RSS
Download PDF
DOI: 10.1055/s-0037-1615026
Low-dose Oral Vitamin K Reliably Reverses Over-anticoagulation due to Warfarin
Publication History
Received
10 December 1997
Accepted after Revision
13 February 1998
Publication Date:
07 December 2017 (online)
Summary
Background: Patients receiving long-term warfarin frequently develop asymptomatic excessive prolongation of their international normalized ratio (INR) results. The most appropriate management strategy in these patients is unknown. This prospective cohort study was designed to address whether 1 mg of oral vitamin K effectively reduces the INR value of such patients. Methods: A prospective cohort study was performed in two tertiary care teaching hospitals, in which 62 patients receiving warfarin who had INR values between 4.5 and 10.0 received 1 mg of oral vitamin K. All patients had daily INR values and clinical assessments performed. Results: The mean INR value at presentation was 5.79 (95% confidence interval (CI) 5.48 to 6.09, range 4.5 to 9.5). Sixteen hours after receiving the 1 mg of oral vitamin K, the mean INR was 2.86 (95% CI 2.50 to 3.23). On the second and third days after vitamin K, the mean INR values were 2.20 (1.93 to 2.47) and 2.14 (1.85 to 2.44), respectively. No adverse events or bleeding complications were observed. In three patients (6%) the INR value rose between the time of vitamin K administration and the next INR determination; two patients received a further 2 mg dose of subcutaneous vitamin K. Conclusions: In patients receiving warfarin who have asymptomatic excessive prolongations in their INR results, 1 mg of oral vitamin K reliably reduces the INR to the therapeutic range within 24 h. This therapy is more convenient, less expensive, and might be safer than parenteral vitamin K. Thus, it should be considered in all non-bleeding patients receiving warfarin, who present with INR results of 4.5 to 9.5.
Dr. Crowther is the recipient of a Medical Research Council of Canada Research Fellowship.
Dr. Ginsberg is a Career Investigator of the Heart and Stroke Foundation of Ontario.
-
References
- 1 Landefeld CS, Goldman L. Major bleeding in outpatients treated with warfarin: incidence and prediction by factors known at the start of outpatient therapy. American Journal of Medicine 1989; 87: 144-52.
- 2 Landefeld CS, Beyth RJ. Anticoagulant-related bleeding: clinical epidemiology, prediction, and prevention. American Journal of Medicine 1993; 95: 315-28.
- 3 Fihn SD, McDonell M, Martin D, Henikoff J, Vermes D, Kent D, White RH. Risk factors for complications of chronic anticoagulation. A multi-center study. Warfarin Optimized Outpatient Follow-up Study Group. Annals of Internal Medicine 1993; 118: 511-20.
- 4 Hylek EM, Singer DE. Risk factors for intracranial hemorrhage in out-patients taking warfarin. Annals of Internal Medicine 1994; 120: 897-902.
- 5 Anonymous. Bleeding during antithrombotic therapy in patients with atrial fibrillation. The Stroke Prevention in Atrial Fibrillation Investigators. Archives of Internal Medicine 1996; 156: 409-16.
- 6 Hyers TM, Hull RD, Weg JG. Antithrombotic therapy for venous thromboembolic disease. Chest 1995; 108 (04) 335S-51S.
- 7 Turpie AG, Gent M, Laupacis A, Latour Y, Gunstensen J, Basile FKM, Hirsh J. A comparison of aspirin with placebo in patients treated with warfarin after heart-valve replacement. New England Journal of Medicine 1993; 329: 524-9.
- 8 Glover JJ, Morrill GB. Conservative treatment of overanticoagulated patients. Chest 1995; 108: 987-90.
- 9 Perry DJ, Kimball Jr. DB. Low dose vitamin K for excessively anticoagulated prosthetic valve patients. Military Medicine 1982; 147: 836-7.
- 10 Shetty HG, Backhouse G, Bentley DP, Routledge PA. Effective reversal of warfarin-induced excessive anticoagulation with low dose vitamin K1. Thromb Haemost 1992; 67: 13-5.
- 11 Andersen P, Godal HC. Predictable reduction in anticoagulant activity of warfarin by small amounts of vitamin K. Acta Medica Scandinavia 1975; 198: 269-70.
- 12 Taberner DA, Thomson JM, Poller L. Comparison of prothrombin complex concentrate and vitamin K1 in oral anticoagulant reversal. British Medical Journal 1976; 76 6027 83-5.
- 13 Vermeer C, Hamulyak K. Pathophysiology of vitamin K-deficiency and oral anticoagulants. Thromb Haemost 1991; 66: 153-9.
- 14 Tuppal R, Tremaine R. Cutaneous eruption from vitamin K1 injection. Journal of the American Academy of Dermatology 1992; 27: 105-6.
- 15 Tsuboi R, Ogawa H. Skin eruption caused by fat-soluble vitamin K injection. Journal of the American Academy of Dermatology. 1988 18 (2 Pt).
- 16 Joyce JP, Hood AF, Weiss MM. Persistent cutaneous reaction to intramuscular vitamin K injection. Archives of Dermatology 1988; 124: 27-8.
- 17 Kay MH, Duvic M. Reactive annular erythema after intramuscular vitamin K. Cutis 1986; 37: 445-8.
- 18 Finkelstein H, Champion MC, Adam JE. Cutaneous hypersensitivity to vitamin K1 injection. Journal of the American Academy of Dermatology 1987; 16: 540-5.
- 19 Sanders MN, Winkelmann RK. Cutaneous reactions to vitamin K. Journal of the American Academy of Dermatology 1988; 19: 699-704.
- 20 Martinez-Abad M, Delgado F, Palop V, Morales-Olivas FJ. Vitamin K1 and anaphylactic shock. DICP 1991; 25: 871-2.
- 21 Lemlich G, Green M, Phelps R, Lebwohl M, Don P, Gordon M. Cutaneous reactions to vitamin K1 injections. Journal of the American Academy of Dermatology 1993; 28: 345-7.
- 22 Martin JC. Anaphylactoid reactions and vitamin K. Medical Journal of Australia 1991; 155: 851.
- 23 de la Rubia J, Grau E, Montserrat I, Zuazu I, Paya A. Anaphylactic shock and vitamin K1. Annals of Internal Medicine 1989; 110: 943.
- 24 Havel M, Muller M, Graninger W, Kurz R, Lindemayr H. Tolerability of a new vitamin K1 preparation for parenteral administration to adults: one case of anaphylactoid reaction. Clinical Therapeutics 1987; 9: 373-9.
- 25 Porterfield LM. Watch for severe reactions to vitamin K. RN 1993; 56: 87.
- 26 Martin JE, Lutomski DM. Warfarin resistance and enteral feedings. Jpen: Journal of Parenteral & Enteral Nutrition 1989; 13: 206-8.
- 27 Cosgriff SW. The effectiveness of an oral vitamin K1 in controlling excessive hypoprothrombinemia during anticoagulant therapy. Annals of Internal Medicine 1956; 45: 14-22.
- 28 Weibert R, Le DT, Kayser SR, Rapaport SI. Correction of excessive anticoagulation with low-dose oral vitamin K1. Annals of Internal Medicine 1997; 126 (12) 959-62.
- 29 Pengo V, Banzato A, Garelli E, Zasso A, Biasiolo A. Reversal of excessive effect of regular anticoagulation: low oral dose of phytonadione (vitamin K1) compared with warfarin discontinuation. Blood Coagulation & Fibrinolysis 1993; 4: 739-41.