warfarin overdose

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An algorithm for the management of bleeding and excessive anticoagulation was devised (3):

  • if 3.0 < INR < 6.0 (target INR 2.5) then:
    • reduce warfarin dose/stop warfarin
    • restart warfarin when INR < 5.0
  • if 4.0 < INR < 6.0 (target INR 3.5)
    • reduce warfarin/stop warfarin
    • restart warfarin when INR < 5.0
  • if 6.0 < INR < 8.0 and no bleeding or minor bleeding then:
    • stop warfarin
    • restart when INR < 5.0
  • if INR > 8.0 and no bleeding or minor bleeding then:
    • stop warfarin
    • restart warfarin when INR < 5.0
    • if other risk factors for bleeding then give 0.5-2.5mg of oral vitamin K

  • if major bleeding then:
    • stop warfarin
    • managing bleeding and excessive anticoagulation
      • reversal of anticoagulation with vitamin K is achieved more rapidly with intravenous administration than oral administration
      • in the original guideline an option of 5 mg of vitamin K orally or intravenously was recommended for patients with major bleeding (1), in addition to factor replacement therapy with either a factor concentrate or fresh frozen plasma (FFP). Subsequent guidance (5) now considers that, in patients with major bleeding, reversal with intravenous vitamin K is preferable. A dose of either 5 or 10 mg is recommended.
        • complete and rapid reversal of over-anticoagulation is more readily achieved with a factor concentrate than with FFP
        • intravenous vitamin K should be given if reversal is to be sustained
      • the guidance recommends (5,6)
        • reversal of anticoagulation in patients with major bleeding requires administration of a factor concentrate (prothrombin factor concentrate) in preference to FFP, when this is available and administration of intravenous rather than oral vitamin K

Unexpected bleeding at therapeutic levels:

  • investigate for possible cause e.g. alimentary or renal disease

Notes:

  • there is evidence that in patients receiving warfarin and who had an INR between 4.5 and 10.0, low dose vitamin K lowered the INR to between 1.8 and 3.2 the day after administration (2)
    • however a more recent large randomized controlled trail including more than 700 patients with INR values between 4.5 and 10.0 failed to show a statistically significant reduction in major bleeding events in the group of patients randomized to 1.25 mg of oral vitamin K compared with the group of patients randomized to placebo (3)

Reference:

  1. Guidelines on oral anticoagulation: third edition . British Journal of Haematology 1998;101 (2): 374-387
  2. Crowther MA et al. Treatment of warfarin-associated coagulopathy with oral vitamin K: a randomised controlled trial. Lancet 2000; 356: 1551-3.
  3. Crowther MA, Ageno W, Garcia D, et al. Effectiveness of low dose oral vitamin K for patients with elevated INR values: results of randomized trial examining clinical outcomes. J Thromb Haemost 2007;5 Suppl 2:P-S-219
  4. MeReC Bulletin (1997); 8(1): 1-4.
  5. Guidelines on oral anticoagulation (warfarin): third edition - 2005 update. British Journal of Haematol 2006; 132(3): 277-85
  6. NICE (November 2015). Blood transfusion

Last reviewed 01/2018

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