Journal of the Neurological Sciences 337 (2014) 238

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Letter to the Editor Does a location predilection exist for warfarin associated intracerebral hemorrhage? I have read, with great interest, a recently published article in the Journal of Neurological Sciences by Ma et al. titled ‘Warfarin-associated intracerebral hemorrhage: Volume, anticoagulation intensity and location’ [1]. In this retrospective analysis, the authors sought to identify clinical and radiographic factors associated with intracerebral hemorrhage (ICH) in patients taking warfarin. A total of 404 patients were included in the study comprised of 69 patients on warfarin therapy (17%) and 335 patients not taking warfarin (83%). The baseline medical comorbidities, including diabetes (P = 0.004), ischemic heart disease (P b 0.001), atrial fibrillation (P b 0.001), and previous ischemic stroke (P b 0.001), of the patients in the warfarin cohort were more severe than those in the non-warfarin cohort, and the patients in the warfarin cohort were older (P = 0.031). The patients taking warfarin had significantly larger ICH volumes than those who were not (P = 0.046), and the mortality rate in the warfarin cohort was significantly higher than in the non-warfarin cohort (P = 0.003). There was no significant association between admission international normalized ratio (INR) and ICH volume (P = 0.120). However, there were more brainstem ICHs in the warfarin cohort than in the nonwarfarin cohort (P = 0.012). Furthermore, multivariate analysis identified INR greater than 3.0 to be an independent predictor of infratentorial ICH (P = 0.004). The authors conclude that poorer ICH outcomes in patients on warfarin therapy were secondary to not only larger hematoma volumes, but also to a preponderance of infratentorial ICH location. While the aim of the study is well-intentioned, I believe the results of the statistical analysis are over-interpreted. The number of the patients on warfarin with infratentorial ICHs was only 15, including five located in the cerebellum and 10 located in the brainstem. To infer a predilection of warfarin-associated ICH for the posterior fossa based on such a few number of cases may be too bold. The ICH score is the most widely utilized grading system for predicting ICH patient outcomes [2]. Comprised of the factors patient age, patient Glasgow Coma Scale at presentation, ICH volume, supratentorial versus infratentorial ICH location, and presence of intraventricular hemorrhage, the ICH score estimates 30-day mortality. Posterior circulation strokes are generally more devastating than their anterior circulation counterparts due to the highly eloquent nature of the brainstem. The relatively restricted anatomy of the posterior fossa

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further increases the relative risk of neurological deterioration from infratentorial compared to supratentorial ICHs. Additionally, the only class I evidence for the surgical evacuation of ICH remains for those located in the cerebellum which are resulting in neurological dysfunction secondary to local mass effect or obstructive hydrocephalus [3]. However, due to the significantly increased surgical complication rates with patients fully anticoagulated on warfarin and the poorer overall medical condition of the warfarin cohort patients in this study, surgical evacuation may have been deemed too dangerous in cerebellar ICH patients taking warfarin. Therefore cerebellar ICH patients not taking warfarin may have been preferentially treated with emergent surgical evacuation at referring institutions while anticoagulated cerebellar ICH patients were transferred to the authors' institution, a stroke center, for management of a more complex cerebrovascular pathology. This referral bias may have artificially increased the proportion of infratentorial ICHs in patients on warfarin as observed in this study. In summary, the authors should be congratulated for rigorous, multivariate statistical analysis of a large number of ICH patients. Future studies are needed to determine whether ICHs affecting patients taking anticoagulant medications, such as warfarin, are truly predisposed to a specific location. Furthermore, it remains to be determined whether findings such as these will impact management strategies and, ultimately, clinical outcomes for patients afflicted with warfarin-associated ICH. References [1] Ma M, Meretoja A, Churilov L, Sharma GJ, Christensen S, Liu X, et al. Warfarinassociated intracerebral hemorrhage: volume, anticoagulation intensity and location. J Neurol Sci 2013;332(1–2):75–9. [2] Hemphill, III JC, Bonovich DC, Besmertis L, Manley GT, Johnston SC. The ICH score: a simple, reliable grading scale for intracerebral hemorrhage. Stroke 2001;32(4):891–7. [3] Morgenstern LB, Hemphill III JC, Anderson C, Becker K, Broderick JP, Connolly Jr ES, et al. Guidelines for the management of spontaneous intracerebral hemorrhage: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2010;41(9):2108–29.

Dale Ding University of Virginia, Department of Neurological Surgery, P.O. Box 800212, Charlottesville, VA 22908, United States Tel.: +1 434 924 2203; fax: +1 434 243 6726. E-mail address: [email protected]

27 September 2013

Does a location predilection exist for warfarin associated intracerebral hemorrhage?

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