Idarucizumab Improves Outcome in Murine Brain Hemorrhage Related to Dabigatran

Ann Neurol. 2015 Jul;78(1):137-41. doi: 10.1002/ana.24421.

Abstract

Lack of specific antidotes is a major concern in intracerebral hemorrhage (ICH) related to direct anticoagulants including dabigatran (OAC-ICH). We examined the efficacy of idarucizumab, an antibody fragment binding to dabigatran, in a mouse model of OAC-ICH. Dabigatran etexilate (DE) dose-dependently prolonged diluted thrombin time and tail-vein bleeding time, which were reversed by idarucizumab. Pretreatment with DE increased intracerebral hematoma volume and cerebral hemoglobin content. Idarucizumab in equimolar dose prevented excess hematoma expansion for both DE doses. In more extensive ICH, idarucizumab significantly reduced mortality. Thus, idarucizumab prevents excess intracerebral hematoma formation in mice anticoagulated with dabigatran and reduces mortality.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal, Humanized / pharmacology*
  • Anticoagulants / pharmacology
  • Antithrombins / adverse effects*
  • Benzimidazoles / adverse effects
  • Benzimidazoles / antagonists & inhibitors*
  • Bleeding Time
  • Blood Coagulation / drug effects*
  • Brain / drug effects*
  • Brain / pathology
  • Cerebral Hemorrhage / chemically induced*
  • Dabigatran
  • Disease Models, Animal
  • Hematoma / pathology
  • Mice
  • Thrombin Time
  • Warfarin / pharmacology
  • beta-Alanine / adverse effects
  • beta-Alanine / analogs & derivatives*
  • beta-Alanine / antagonists & inhibitors

Substances

  • Antibodies, Monoclonal, Humanized
  • Anticoagulants
  • Antithrombins
  • Benzimidazoles
  • beta-Alanine
  • Warfarin
  • idarucizumab
  • Dabigatran