Does dabigatran increase the risk of delayed hematoma expansion in a rat model of collagenase-induced intracerebral hemorrhage?

Shunsuke Tanoue, Joji Inamasu, Masayuki Yamada, Hiroshi Toyama, Yuichi Hirose

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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 (mm3) 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 (mm3) 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.

Original languageEnglish
Pages (from-to)374-380
Number of pages7
JournalJournal of Stroke and Cerebrovascular Diseases
Volume24
Issue number2
DOIs
Publication statusPublished - 01-02-2015

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Cerebral Hemorrhage
Collagenases
Hematoma
Warfarin
Dabigatran
Control Groups
Natural History
Wistar Rats
Magnetic Resonance Imaging

All Science Journal Classification (ASJC) codes

  • Surgery
  • Rehabilitation
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

Cite this

@article{7fe363d878b948fb8e8e87ed80776111,
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 (mm3) 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 (mm3) 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.",
author = "Shunsuke Tanoue and Joji Inamasu and Masayuki Yamada and Hiroshi Toyama and Yuichi Hirose",
year = "2015",
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T1 - Does dabigatran increase the risk of delayed hematoma expansion in a rat model of collagenase-induced intracerebral hemorrhage?

AU - Tanoue, Shunsuke

AU - Inamasu, Joji

AU - Yamada, Masayuki

AU - Toyama, Hiroshi

AU - Hirose, Yuichi

PY - 2015/2/1

Y1 - 2015/2/1

N2 - 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 (mm3) 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 (mm3) 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.

AB - 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 (mm3) 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 (mm3) 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.

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