Does Dabigatran Increase the Risk of Delayed Hematoma Expansion in a Rat Model of Collagenase-induced Intracerebral Hemorrhage? Shunsuke Tanoue, MD,*† Joji Inamasu, MD, PhD,* Masayuki Yamada, PhD,‡ Hiroshi Toyama, MD, PhD,x and Yuichi Hirose, MD, PhD* Background: Delayed hematoma expansion is common in intracerebral hemorrhage (ICH) patients using warfarin. Dabigatran induces fewer hemorrhagic complications compared with warfarin. However, the natural history of dabigatran-related ICH re- mains unclear. This study aims to clarify whether dabigatran increases the risk of de- layed hematoma expansion in a rat ICH model. Methods: Male Wistar rats were treated with 2 dosages of dabigatran etexilate (DE: 10 mg/kg, n 5 4; 20 mg/kg, n 5 3) 30 minutes before ICH induction using intraparenchymal collagenase infu- sion. Five rats that received saline were used as controls. Magnetic resonance imaging was performed 24 and 48 hours after ICH induction, and serial hematoma volume measurements were obtained using T2-weighted images. Expanded hema- toma volumes were calculated by subtracting hematoma volumes at 48 hours from those at 24 hours; the hematoma expansion rate was defined as the ratio of the expanded hematoma volume to that at 24 hours. Results: The mean hematoma volumes (mm 3 ) at 24 hours were 13.3 6 3.3 in the control group, 14.9 6 2.0 in the 10 mg/kg DE group, and 18.9 6 7.6 in the 20 mg/kg DE group with no significant intergroup differences (P 5 .26). The mean hematoma volumes at 48 hours (mm 3 ) were 21.7 6 4.9 in the control group, 22.1 6 5.0 in the 10 mg/kg DE group, and 23.4 6 5.8 in the 20 mg/kg DE group with no significant intergroup differences (P 5 .90). Consequently, there were no significant intergroup differences in the hematoma expansion rates (P 5 .33). Conclusions: This experimental study of a rat ICH model indicates that dabigatran-related ICH may not increase the risk of de- layed hematoma expansion. Key Words: Dabigatran—delayed hematoma expansion—intracerebral hemorrhage—magnetic resonance imaging—warfarin. Ó 2015 by National Stroke Association The number of patients with embolic stroke because of atrial fibrillation (AF) is increasing in accordance with the rapidly aging general population. 1-3 Oral anticoagulant therapy has been the mainstay of preventive treatment against primary or secondary stroke in AF patients, and until recently, only warfarin, a vitamin K inhibitor, has From the *Department of Neurosurgery, Fujita Health University School of Medicine, Toyoake; †Department of Neurosurgery, Self- Defense Forces Central Hospital, Tokyo; ‡Department of Radiology, Fujita Health University School of Medical Sciences, Toyoake; and xDepartment of Radiology, Fujita Health University School of Medi- cine, Toyoake, Japan. Received July 10, 2014; revision received September 1, 2014; accepted September 3, 2014. Sources of funding: J.I. received financial support from the Japan Brain Foundation and Fujita Research Foundation. Disclosure/conflict of interest: None of the authors have conflict of interests with Boehringer Ingelheim, the manufacturer of DE (Pra- zaxa). DE capsules were provided by the manufacturer. All the au- thors who are members of the Japan Stroke Society have submitted the conflict of interest statement form to the Society. Address correspondence to Joji Inamasu, MD, PhD, Department of Neurosurgery, Fujita Health University School of Medicine, 1-98 Kut- sukake, Toyoake 470-1192, Japan. E-mail: inamasu@fujita-hu.ac.jp. 1052-3057/$ - see front matter Ó 2015 by National Stroke Association http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2014.09.010 374 Journal of Stroke and Cerebrovascular Diseases, Vol. 24, No. 2 (February), 2015: pp 374-380