title: Anticoagulation with the oral direct thrombin inhibitor dabigatran does not enlarge hematoma volume in experimental intracerebral hemorrhage.
abstract: BACKGROUND
  The direct thrombin inhibitor dabigatran etexilate (DE) may constitute a future replacement of vitamin K antagonists for long-term anticoagulation. Whereas warfarin pretreatment is associated with greater hematoma expansion after intracerebral hemorrhage (ICH), it remains unclear what effect direct thrombin inhibitors would have. Using different experimental models of ICH, this study compared hematoma volume among DE-treated mice, warfarin-treated mice, and controls.
  
  
  RESULTS
  CD-1 mice were fed with DE or warfarin. Sham-treated mice served as controls. At the time point of ICH induction, DE mice revealed an increased activated partial thromboplastin time compared with controls (mean±SD 46.1 ± 5.0 versus 18.0 ± 1.5 seconds; P=0.022), whereas warfarin pretreatment resulted in a prothrombin time prolongation (51.4 ± 17.9 versus 10.4 ± 0.3 seconds; P<0.001). Twenty-four hours after collagenase-induced ICH formation, hematoma volume was 3.8 ± 2.9 μL in controls, 4.8 ± 2.7 μL in DE mice, and 14.5 ± 11.8 μL in warfarin mice (n=16; Welch ANOVA between-group differences P=0.007; posthoc analysis with the Dunnett method: DE versus controls, P=0.899; warfarin versus controls, P<0.001; DE versus warfarin, P=0.001). In addition, a model of laser-induced cerebral microhemorrhage was applied, and the distances that red blood cells and blood plasma were pushed into the brain were quantified. Warfarin mice showed enlarged red blood cell and blood plasma diameters compared to controls, but no difference was found between DE mice and controls.
  
  
  CONCLUSIONS
  In contrast with warfarin, pretreatment with DE did not increase hematoma volume in 2 different experimental models of ICH. In terms of safety, this observation may represent a potential advantage of anticoagulation with DE over warfarin.
authors.affiliation: Department of Neurology, Johann Wolfgang Goethe-University, Frankfurt am Main, Germany.
authors.forename: Arne
authors.initials: A
authors.lastname: Lauer
authors.forename: Flor A
authors.initials: FA
authors.lastname: Cianchetti
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Van Cott
authors.forename: Frieder
authors.initials: F
authors.lastname: Schlunk
authors.forename: Elena
authors.initials: E
authors.lastname: Schulz
authors.forename: Waltraud
authors.initials: W
authors.lastname: Pfeilschifter
authors.forename: Helmuth
authors.initials: H
authors.lastname: Steinmetz
authors.forename: Chris B
authors.initials: CB
authors.lastname: Schaffer
authors.forename: Eng H
authors.initials: EH
authors.lastname: Lo
authors.forename: Christian
authors.initials: C
authors.lastname: Foerch
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000925:Anticoagulants / Q000008:administration & dosage*; D058833:Antithrombin Proteins / Q000008:administration & dosage*; D001562:Benzimidazoles / Q000008:administration & dosage*; D002543:Cerebral Hemorrhage / Q000139:chemically induced / Q000150:complications*; D017364:Collagenases / Q000008:administration & dosage; D000069604:Dabigatran; D006406:Hematoma / Q000175:diagnosis* / Q000209:etiology* / Q000503:physiopathology; D007267:Injections; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008856:Microscopy, Fluorescence; D010314:Partial Thromboplastin Time; D011725:Pyridines / Q000008:administration & dosage*; D013997:Time Factors; D014859:Warfarin / Q000008:administration & dosage
chemical_list: D000925:Anticoagulants; D058833:Antithrombin Proteins; D001562:Benzimidazoles; D011725:Pyridines; D014859:Warfarin; D017364:Collagenases; D000069604:Dabigatran