Download PDF
Thromb Haemost 1998; 79(06): 1116-1118
DOI: 10.1055/s-0037-1615026
Rapid Communication
Schattauer GmbH

Low-dose Oral Vitamin K Reliably Reverses Over-anticoagulation due to Warfarin

M. A. Crowther
1   From the Hamilton Civic Hospitals Research Centre, Henderson General Hospital, Hamilton, ON, Canada
,
D. Donovan
1   From the Hamilton Civic Hospitals Research Centre, Henderson General Hospital, Hamilton, ON, Canada
,
L. Harrison
1   From the Hamilton Civic Hospitals Research Centre, Henderson General Hospital, Hamilton, ON, Canada
,
J. McGinnis
1   McMaster University Medical Centre, Hamilton, ON, Canada
,
J. Ginsberg
1   McMaster University Medical Centre, Hamilton, ON, Canada
› Author Affiliations
Further Information

Publication History

Received 10 December 1997

Accepted after Revision 13 February 1998

Publication Date:
07 December 2017 (online)

    Permissions and Reprints

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.
    CrossrefPubMedGoogle Scholar
  • 2 Landefeld CS, Beyth RJ. Anticoagulant-related bleeding: clinical epidemiology, prediction, and prevention. American Journal of Medicine 1993; 95: 315-28.
    CrossrefPubMedGoogle Scholar
  • 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.
    CrossrefPubMedGoogle Scholar
  • 4 Hylek EM, Singer DE. Risk factors for intracranial hemorrhage in out-patients taking warfarin. Annals of Internal Medicine 1994; 120: 897-902.
    CrossrefPubMedGoogle Scholar
  • 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.
    CrossrefPubMedGoogle Scholar
  • 6 Hyers TM, Hull RD, Weg JG. Antithrombotic therapy for venous thromboembolic disease. Chest 1995; 108 (04) 335S-51S.
    CrossrefPubMedGoogle Scholar
  • 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.
    CrossrefPubMedGoogle Scholar
  • 8 Glover JJ, Morrill GB. Conservative treatment of overanticoagulated patients. Chest 1995; 108: 987-90.
    CrossrefPubMedGoogle Scholar
  • 9 Perry DJ, Kimball Jr. DB. Low dose vitamin K for excessively anticoagulated prosthetic valve patients. Military Medicine 1982; 147: 836-7.
    CrossrefPubMedGoogle Scholar
  • 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.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 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.
    PubMedGoogle Scholar
  • 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.
    PubMedGoogle Scholar
  • 13 Vermeer C, Hamulyak K. Pathophysiology of vitamin K-deficiency and oral anticoagulants. Thromb Haemost 1991; 66: 153-9.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 14 Tuppal R, Tremaine R. Cutaneous eruption from vitamin K1 injection. Journal of the American Academy of Dermatology 1992; 27: 105-6.
    CrossrefPubMedGoogle Scholar
  • 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).
    PubMedGoogle Scholar
  • 16 Joyce JP, Hood AF, Weiss MM. Persistent cutaneous reaction to intramuscular vitamin K injection. Archives of Dermatology 1988; 124: 27-8.
    CrossrefPubMedGoogle Scholar
  • 17 Kay MH, Duvic M. Reactive annular erythema after intramuscular vitamin K. Cutis 1986; 37: 445-8.
    PubMedGoogle Scholar
  • 18 Finkelstein H, Champion MC, Adam JE. Cutaneous hypersensitivity to vitamin K1 injection. Journal of the American Academy of Dermatology 1987; 16: 540-5.
    CrossrefPubMedGoogle Scholar
  • 19 Sanders MN, Winkelmann RK. Cutaneous reactions to vitamin K. Journal of the American Academy of Dermatology 1988; 19: 699-704.
    CrossrefPubMedGoogle Scholar
  • 20 Martinez-Abad M, Delgado F, Palop V, Morales-Olivas FJ. Vitamin K1 and anaphylactic shock. DICP 1991; 25: 871-2.
    PubMedGoogle Scholar
  • 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.
    CrossrefPubMedGoogle Scholar
  • 22 Martin JC. Anaphylactoid reactions and vitamin K. Medical Journal of Australia 1991; 155: 851.
    PubMedGoogle Scholar
  • 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.
    PubMedGoogle Scholar
  • 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.
    PubMedGoogle Scholar
  • 25 Porterfield LM. Watch for severe reactions to vitamin K. RN 1993; 56: 87.
    PubMedGoogle Scholar
  • 26 Martin JE, Lutomski DM. Warfarin resistance and enteral feedings. Jpen: Journal of Parenteral & Enteral Nutrition 1989; 13: 206-8.
    CrossrefPubMedGoogle Scholar
  • 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.
    CrossrefPubMedGoogle Scholar
  • 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.
    CrossrefPubMedGoogle Scholar
  • 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.
    CrossrefPubMedGoogle Scholar