Warfarin, hematoma expansion, and outcome of intracerebral hemorrhage

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Abstract
Background: Warfarin increases mortality of intracerebral hemorrhage (ICH). The authors investigated whether this effect reflects increased baseline ICH volume at presentation or increased ICH expansion. Methods: Subjects were drawn from an ongoing prospective cohort study of ICH outcome. The effect of warfarin on baseline ICH volume was studied in 183 consecutive cases of supratentorial ICH age ≥ 18 years admitted to the emergency department over a 5-year period. Baseline ICH volume was determined using computerized volumetric analysis. The effect of warfarin on ICH expansion (increase in volume ≥ 33% of baseline) was analyzed in 70 consecutive cases in whom ICH volumes were measured on all subsequent CT scans up to 7 days after admission. Multivariable analysis was used to determine warfarin’s influence on baseline ICH, ICH expansion, and whether warfarin’s effect on ICH mortality was dependent on baseline volume or subsequent expansion. Results: There was no effect of warfarin on initial volume. Predictors of larger baseline volume were hyperglycemia (p < 0.0001) and lobar hemorrhage (p < 0.0001). Warfarin patients were at increased risk of death, even when controlling for ICH volume at presentation. Warfarin was the sole predictor of expansion (OR 6.2, 95% CI 1.7 to 22.9) and expansion in warfarin patients was detected later in the hospital course compared with non-warfarin patients (p < 0.001). ICH expansion showed a trend toward increased mortality (OR 3.5, 95% CI 0.7 to 8.9, p = 0.14) and reduced the marginal effect of warfarin on ICH mortality. Conclusions: Warfarin did not increase ICH volume at presentation but did raise the risk of in-hospital hematoma expansion. This expansion appears to mediate part of warfarin’s effect on ICH mortality.