Warfarin-related intraventricular hemorrhage: imaging and outcome

Abstract

Objective: Oral anticoagulation therapy (OAT) with warfarin increases mortality and disability after intracerebral hemorrhage (ICH), the result of increased ICH volume and risk of hematoma expansion. We investigated whether OAT also influences risk of development of intraventricular hemorrhage (IVH), the volume of IVH and IVH expansion, and whether IVH is a substantive mediator of the overall effect of OAT on ICH outcome.

Methods: We performed a retrospective analysis of a prospectively collected single-center cohort of 1,879 consecutive ICH cases (796 lobar, 865 deep, 153 cerebellar, 15 multiple location, 50 primary IVH) from 1999 to 2009. ICH and IVH volumes at presentation, as well as hematoma expansion (>33% or >6 mL increase) and IVH expansion (>2 mL increase), were determined using established semiautomated methods. Outcome was assessed at 90 days using either the modified Rankin Scale or Glasgow Outcome Scale.

Results: Warfarin use was associated with IVH risk, IVH volume at presentation, and IVH expansion in both lobar and deep ICH (all p < 0.05) in a dose-response relationship with international normalized ratio. Warfarin was associated with poor outcome in both lobar and deep ICH (p < 0.01), and >95% of this effect was accounted for by baseline ICH and IVH volumes, as well as ICH and IVH expansion.

Conclusion: Warfarin increases IVH volume and risk of IVH expansion in lobar and deep ICH. These findings (along with effects on ICH volume and expansion) likely represent the mechanisms by which anticoagulation worsens ICH functional outcome.

Figure 1. International normalized ratio (INR) and baseline intraventricular hemorrhage (IVH) volume

IVH volumes for lobar ICH (A) and deep ICH (B) are presented and analyzed only when IVH present (IVH volume >0.0 mL). All analyses adjusted for baseline ICH volume. Lobar ICH: p value for comparison across categories (trend-test) = 0.008, deep ICH: p value for comparison across categories (trend-test) = 0.01. * p < 0.05 for comparison with INR <2.0, ** p < 0.01 for comparison with INR <2.0.

Figure 2. International normalized ratio (INR) and intraventricular hemorrhage (IVH) expansion in lobar and deep intracerebral hemorrhage (ICH)

(A) IVH expansion risk for warfarin users (compared to nonusers) and by INR (compared to INR <1.2) for lobar ICH. p Value for comparison across categories (trend-test) = 0.011. (B) IVH expansion risk for warfarin users (compared to nonusers) and by INR (compared to INR <1.2) for deep ICH. p Value for comparison across categories (trend-test) = 0.006. All multivariate analyses adjusted for baseline ICH volume, baseline IVH volume, and ICH expansion. CI = confidence interval; OR = odds ratio.