1. Home>
2. Specialties>
3. Emergency Medicine>
4. Summary and Comment

Warfarin Reversal: Another Door-to-Drug Time Goal

Shorter times to administration of vitamin K or fresh frozen plasma increase the chance for successful reversal of anticoagulation in patients with warfarin-associated intracerebral hemorrhage.

Intracerebral hemorrhage (ICH) accounts for roughly 10% of strokes and 1% of all deaths in the U.S. Patients taking warfarin have a sixfold increased risk for ICH and are likely to have ongoing bleeding. Reversal of anticoagulation is first-line therapy in such cases. To assess the timing and outcomes of therapy with vitamin K and fresh frozen plasma (FFP), these authors retrospectively reviewed all cases of nontraumatic warfarin-associated ICH that presented to a single emergency department from 1998 to 2004.

After exclusions for incomplete records, initial international normalized ratio (INR) 1.4, and do-not-resuscitate orders, 69 of 160 cases were included in the analysis. At 24 hours, 57 patients (83%) had adequate reversal (defined as INR 1.4). In multivariate analyses adjusting for disease severity, researchers found that shorter times to FFP administration and to vitamin K administration each were independently associated with the likelihood of successful reversal (odds ratio, 0.8 for both agents). Neither success of anticoagulation reversal nor dose of FFP or vitamin K affected clinical outcomes at 90 days.

Comment: These authors document delays in reversal of anticoagulation and a correlation between such delays and inadequate reversal at 24 hours. Although there is no direct evidence that reversal saves lives, reversal is certainly desirable in the context of intracranial or other serious hemorrhage.

Why the delays? FFP takes time to obtain, thaw, and hang. With vitamin K, concern about anaphylactoid reactions might result in delays. Although intravenous vitamin K is associated with rare anaphylactoid reactions, such concerns do not have a place in the treatment of life-threatening warfarin-associated hemorrhages. Only 27 deaths from vitamin K anaphylactoid reaction have ever been reported in the English-language literature. (See J Thromb Thrombolysis 2001; 11:175-83). If vitamin K cannot be given intravenously, it should be given orally.

— Daniel J. Pallin, MD, MPH

Dr. Pallin is an attending physician in the Department of Emergency Medicine at Brigham and Women's Hospital in Boston and in the Department of Emergency Medicine at Children's Hospital, Boston. He is also an Instructor in Medicine (Emergency Medicine) at Harvard Medical School.

Published in Journal Watch Emergency Medicine January 17, 2006

Citation(s):

Goldstein JN et al. Timing of fresh frozen plasma administration and rapid correction of coagulopathy in warfarin-related intracerebral hemorrhage. Stroke 2006 Jan; 37:151-5.

• Original article (Subscription may be required)
• Medline abstract (Free)