title: Does dabigatran increase the risk of delayed hematoma expansion in a rat model of collagenase-induced intracerebral hemorrhage?
abstract: 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 remains unclear. This study aims to clarify whether dabigatran increases the risk of delayed hematoma expansion in a rat ICH model.
  
  
  METHODS
  Male Wistar rats were treated with 2 dosages of dabigatran etexilate (DE: 10 mg/kg, n = 4; 20 mg/kg, n = 3) 30 minutes before ICH induction using intraparenchymal collagenase infusion. 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 hematoma 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 ± 3.3 in the control group, 14.9 ± 2.0 in the 10 mg/kg DE group, and 18.9 ± 7.6 in the 20 mg/kg DE group with no significant intergroup differences (P = .26). The mean hematoma volumes at 48 hours (mm(3)) were 21.7 ± 4.9 in the control group, 22.1 ± 5.0 in the 10 mg/kg DE group, and 23.4 ± 5.8 in the 20 mg/kg DE group with no significant intergroup differences (P = .90). Consequently, there were no significant intergroup differences in the hematoma expansion rates (P = .33).
  
  
  CONCLUSIONS
  This experimental study of a rat ICH model indicates that dabigatran-related ICH may not increase the risk of delayed hematoma expansion.
authors.affiliation: Department of Neurosurgery, Fujita Health University School of Medicine, Toyoake, Japan; Department of Neurosurgery, Self-Defense Forces Central Hospital, Tokyo, Japan.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Tanoue
authors.affiliation: Department of Neurosurgery, Fujita Health University School of Medicine, Toyoake, Japan. Electronic address: inamasu@fujita-hu.ac.jp.
authors.forename: Joji
authors.initials: J
authors.lastname: Inamasu
authors.affiliation: Department of Radiology, Fujita Health University School of Medical Sciences, Toyoake, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yamada
authors.affiliation: Department of Radiology, Fujita Health University School of Medicine, Toyoake, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Toyama
authors.affiliation: Department of Neurosurgery, Fujita Health University School of Medicine, Toyoake, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Hirose
mesh_terms: D000818:Animals; D000991:Antithrombins / Q000009:adverse effects*; D001562:Benzimidazoles / Q000009:adverse effects*; D002543:Cerebral Hemorrhage / Q000139:chemically induced* / Q000473:pathology; D017364:Collagenases; D000069604:Dabigatran; D004195:Disease Models, Animal; D006406:Hematoma / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D015091:beta-Alanine / Q000009:adverse effects / Q000031:analogs & derivatives*
chemical_list: D000991:Antithrombins; D001562:Benzimidazoles; D015091:beta-Alanine; D017364:Collagenases; D000069604:Dabigatran
keywords: Dabigatran; delayed hematoma expansion; intracerebral hemorrhage; magnetic resonance imaging; warfarin