Letter by Hifumi et al Regarding Article, “Management and Outcomes of Major Bleeding During Treatment With Dabigatran or Warfarin”
To the Editor:
The article titled “Management and Outcomes of Major Bleeding During Treatment With Dabigatran or Warfarin” by Majeed et al1 was interesting to read. The authors retrospectively reviewed bleeding reports from 5 phase III trials, comparing dabigatran with warfarin among 27 419 patients. They determined that the outcomes after major bleeding events were better in patients on dabigatran than in those on warfarin, as evidenced by a shorter stay in the intensive care unit (dabigatran, 1.6 nights; warfarin, 2.7 nights; P<0.01).
Majeed et al noted that vitamin K was administered in ≈30% patients in the warfarin group; however, details of the treatment received by this group were not described. Although this is an important omission, we have assumed that the treatment was initiated as per the guidelines of “American Heart Association/American College of Cardiology Foundation Guide to Warfarin Therapy.”2 Primarily, rapid reversal of anticoagulation caused by serious bleeding should be treated with a 10-mg dose of vitamin K1 by slow intravenous infusion, with additional doses every 12 hours as required, with supplementation with transfusions of fresh-frozen plasma or prothrombin complex concentrate according to the urgency of the situation.
Warfarin treatment undoubtedly increases the risk of hematoma expansion in patients with warfarin-related intracranial hemorrhage; therefore, it is related to functional outcome and mortality.3 Furthermore, early and persistent reversal of anticoagulation is required acutely to limit hematoma expansion. Majeed et al concluded that appropriate use of reversal agents such as prothrombin complex concentrate and fresh-frozen plasma can improve outcomes among warfarin-treated patients.1 However, if the vitamin K level is severely decreased, coagulopathy may recur within a short interval, despite clotting factor supplementation.
We recently reported a case of absolute vitamin K deficiency diagnosed by measuring serum vitamin K levels in an elderly woman undergoing warfarin therapy for atrial fibrillation.4 She was initially administered intravenous vitamin K (20 mg) and 4 U fresh-frozen plasma, followed by vitamin K (20 mg/d) for 6 days, and her international normalized ratio settled.
Although difficult to distinguish clinically, vitamin K deficiency is classified as either absolute (decreased levels) or relative (normal levels). Warfarin-treated patients with severe coagulopathy are considered to have a relative vitamin K deficiency. However, warfarin-related absolute vitamin K deficiency must be suspected when the international normalized ratio fails to improve with intravenous vitamin K. It is possible that in the absence of aggressive vitamin K supplementation, absolute vitamin K deficiency causes longer intensive care unit stays and greater mortality. Therefore, specific treatment is necessary when absolute vitamin K deficiency is associated with major bleeding.
We believe that serum vitamin K levels should be measured and absolute vitamin K deficiency should be initially treated with aggressive vitamin K administration and supplementation with reversal agents such as prothrombin complex concentrate.
Toru Hifumi, MD
Emergency Medical Center
Kagawa University Hospital
Hiroaki Takada, MD
Nobuaki Kiriu, MD
Division of Critical Care Medicine and Trauma
National Hospital Organization Disaster Medical Center
- © 2014 American Heart Association, Inc.
- Majeed A,
- Hwang HG,
- Connolly SJ,
- Eikelboom JW,
- Ezekowitz MD,
- Wallentin L,
- Brueckmann M,
- Fraessdorf M,
- Yusuf S,
- Schulman S
- Hirsh J,
- Fuster V,
- Ansell J,
- Halperin JL