Published Online
on November 23, 2005

A more recent version of this article appeared on January 1, 2006

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Submitted on June 30, 2005
Revised on July 19, 2005
Accepted on July 27, 2005

Timing of Fresh Frozen Plasma Administration and Rapid Correction of Coagulopathy in Warfarin-Related Intracerebral Hemorrhage

Joshua N. Goldstein MD, PhD^*; Stephen H. Thomas MD, MPh; Virginia Frontiero; Annelise Joseph; Chana Engel BA; Ryan Snider BA; Eric E. Smith MD, MPH; Stephen M. Greenberg MD, PhD; and Jonathan Rosand MD, MSc

From the Department of Emergency Medicine (J.N.G., V.F., A.J.), Brigham & Women’s Hospital; and the Department of Emergency Medicine (S.H.T.), Vascular and Critical Care Neurology (J.N.G., C.E., R.S., E.E.S., S.M.G., J.R.), and Center for Human Genetic Research (J.R.), Massachusetts General Hospital, Boston, Mass.

^* To whom correspondence should be addressed. E-mail: jgoldstein{at}partners.org.

Background and Purpose--Anticoagulation-related intracerebral hemorrhage (ICH) is often fatal, and rapid reversal of anticoagulation is the most appealing strategy currently available for treatment. We sought to determine whether particular emergency department (ED) interventions are effective in reversing coagulopathy and improving outcome.

Methods--Consecutive patients with warfarin-related ICH presenting to an urban tertiary care hospital from 1998 to 2004 were prospectively captured in a database. ED records were retrospectively reviewed for dose and timing of fresh-frozen plasma (FFP) and vitamin K, as well as serial coagulation measures. After excluding patients with incomplete ED records, do-not-resuscitate orders established in the ED, initial international normalized ratio (INR) 1.4, and for whom no repeat INR was performed, 69 patients were available for analysis. The primary outcome was a documented INR 1.4 within 24 hours of ED presentation.

Results--Patients whose INR was successfully reversed within 24 hours had a shorter median time from diagnosis to first dose of FFP (90 minutes versus 210 minutes; P=0.02). In multivariable analysis, shorter time to vitamin K, as well as FFP, predicted INR correction. Every 30 minutes of delay in the first dose of FFP was associated with a 20% decreased odds of INR reversal within 24 hours (odds ratio, 0.8; 95% CI, 0.63 to 0.99). Dosing of FFP and vitamin K had no effect. No ED intervention was associated with improved clinical outcome.

Conclusions--Time to treatment is the most important determinant of 24-hour anticoagulation reversal. Although additional study is required to determine the clinical benefit of rapid reversal of anticoagulation, minimizing delays in FFP administration is a prudent first step in emergency management of warfarin-related ICH.

Key words: anticoagulants • emergency medicine • intracerebral hemorrhage • warfarin

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J. Claude Hemphill, III
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