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Outcome Following Warfarin-Associated Intracerebral Hemorrhage

What factors affect outcome, and which patients with WICH should be restarted on warfarin?

In the setting of atrial fibrillation or a mechanical heart valve, warfarin use is effective for preventing ischemic stroke, but it produces a small increase in risk for intracranial hemorrhage. With warfarin use increasing and the population aging, warfarin-associated intracerebral hemorrhage (WICH) is becoming more common.

In a retrospective series of 88 patients with WICH and international normalized ratios (INR) of 1.5 or greater, investigators identified predictors of poor clinical outcome and hematoma expansion. In univariate analyses, lower initial Glasgow Coma Scale score, larger initial hematoma volume, elevated blood glucose, and hematoma expansion each predicted mortality within both 7 days and 1 year and poor functional outcomes at both hospital discharge and at 1 year. In multivariate analysis (excluding 22 patients with early withdrawal of care), Glasgow Coma Scale score and initial hematoma volume remained significant predictors of mortality. Neither initial INR nor time to INR reversal influenced risk for hematoma expansion.

In a second study, the same authors addressed the important question of when, if ever, warfarin should be restarted for patients who have had WICH. Of 52 WICH patients who survived to hospital discharge, 23 (44%) were restarted on warfarin. During a mean follow-up of 43 months, a nonsignificant trend emerged toward increased early mortality among patients not receiving warfarin. Of the patients who restarted warfarin, five had serious hemorrhages; three of these were fatal. Of those who did not restart warfarin, five had thromboembolic events; one of these was fatal. The incidence of both endpoints combined was similar between groups.

Comment: The predictors of poor outcome following WICH identified in this study are consistent with findings from other studies of intracerebral hemorrhage. Although neither initial INR nor time to INR reversal was associated with hematoma growth, the multivariate analysis excluded patients with low INR or early withdrawal of care. Recent data from the CHANT trial support the commonly held belief that warfarin use increases risk for hematoma expansion (Stroke 2008; 39:2993).

Whether to restart warfarin following WICH is a dilemma, and the second study demonstrates risk with either strategy. For patients with atrial fibrillation who have WICH, a separate decision analysis (Stroke 2003; 34:1710, and JW Neurol Sep 5 2003) remains extremely valuable, despite its overestimation of recurrence risk following lobar hemorrhage. The current evidence suggests that, for patients at highest risk for thromboembolism (e.g., high-risk heart valves or prior thromboembolism attributed to atrial fibrillation), resumption of warfarin should be considered.

— Matthew L. Flaherty, MD

Dr. Flaherty is Assistant Professor of Neurology, University of Cincinnati Academic Health Center, Cincinnati.

Published in Journal Watch Neurology February 10, 2009

Citation(s):

Zubkov AY et al. Predictors of outcome in warfarin-related intracerebral hemorrhage. Arch Neurol 2008 Oct; 65:1320.

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• Medline abstract (Free)

Claassen DO et al. Restarting anticoagulation therapy after warfarin-associated intracerebral hemorrhage. Arch Neurol 2008 Oct; 65:1313.

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• Medline abstract (Free)