title: Idarucizumab Improves Outcome in Murine Brain Hemorrhage Related to Dabigatran.
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.
authors.affiliation: Department of Neurology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Shin-Young
authors.initials: SY
authors.lastname: Na
authors.affiliation: Department of Neurology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Mracsko
authors.affiliation: Department of Cardiometabolic Research, Boehringer Ingelheim, Biberach, Germany.
authors.forename: Joanne
authors.initials: J
authors.lastname: van Ryn
authors.affiliation: Department of Neurology, University of Heidelberg, Heidelberg, Germany.|Division of Brain Sciences, Imperial College London, London, United Kingdom.
authors.forename: Roland
authors.initials: R
authors.lastname: Veltkamp
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology*; D000925:Anticoagulants / Q000494:pharmacology; D000991:Antithrombins / Q000009:adverse effects*; D001562:Benzimidazoles / Q000009:adverse effects / Q000037:antagonists & inhibitors*; D001760:Bleeding Time; D001777:Blood Coagulation / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D002543:Cerebral Hemorrhage / Q000139:chemically induced*; D000069604:Dabigatran; D004195:Disease Models, Animal; D006406:Hematoma / Q000473:pathology; D051379:Mice; D013918:Thrombin Time; D014859:Warfarin / Q000494:pharmacology; D015091:beta-Alanine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000925:Anticoagulants; D000991:Antithrombins; D001562:Benzimidazoles; D015091:beta-Alanine; D014859:Warfarin; C000594745:idarucizumab; D000069604:Dabigatran