title: Imaging of contrast medium extravasation in anticoagulation-associated intracerebral hemorrhage with dual-energy computed tomography.
abstract: OBJECTIVE
  Contrast medium extravasation (CE) in intracerebral hemorrhage (ICH) is a marker of ongoing bleeding and a predictor of hematoma expansion. The aims of the study were to establish an ICH model in which CE can be quantified, characterized in ICH during warfarin and dabigatran anticoagulation, and to evaluate effects of prothrombin complex concentrates on CE in warfarin-associated ICH.
  
  
  METHODS
  CD1-mice were pretreated orally with warfarin, dabigatran, or vehicle. Prothrombin complex concentrates were administered in a subgroup of warfarin-treated mice. ICH was induced by stereotactic injection of collagenase VIIs into the right striatum. Contrast agent (350 μL Isovue 370 mg/mL) was injected intravenously after ICH induction (2-3.5 hours). Thirty minutes later, mice were euthanized, and CE was measured by quantifying the iodine content in the hematoma using dual-energy computed tomography.
  
  
  RESULTS
  The optimal time point for contrast injection was found to be 3 hours after ICH induction, allowing detection of both an increase and a decrease of CE using dual-energy computed tomography. CE was higher in the warfarin group compared with the controls (P=0.002). There was no significant difference in CE between dabigatran-treated mice and controls. CE was higher in the sham-treated warfarin group than in the prothrombin complex concentrates-treated warfarin group (P<0.001).
  
  
  CONCLUSIONS
  Dual-energy computed tomography allows quantifying CE, as a marker of ongoing bleeding, in a model of anticoagulation-associated ICH. Dabigatran induces less CE in ICH than warfarin and consequently reduces risks of hematoma expansion. This constitutes a potential safety advantage of dabigatran over warfarin. Nevertheless, in case of warfarin anticoagulation, prothrombin complex concentrates reduce this side effect.
authors.affiliation: From the Department of Neurology, Goethe-University, Frankfurt am Main, Germany (S.-Y.W., F.S., A.L., H.S., C.F.); Neuroprotection Research Laboratory, Massachusetts General Hospital, Charlestown (S.-Y.W., F.S., H.K., W.L., K.H., E.L.); and Department of Radiology, Massachusetts General Hospital, Boston (J.D., R.G.).
authors.forename: Sae-Yeon
authors.initials: SY
authors.lastname: Won
authors.forename: Frieder
authors.initials: F
authors.lastname: Schlunk
authors.forename: Julien
authors.initials: J
authors.lastname: Dinkel
authors.forename: Hulya
authors.initials: H
authors.lastname: Karatas
authors.forename: Wendy
authors.initials: W
authors.lastname: Leung
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Hayakawa
authors.forename: Arne
authors.initials: A
authors.lastname: Lauer
authors.forename: Helmuth
authors.initials: H
authors.lastname: Steinmetz
authors.forename: Eng H
authors.initials: EH
authors.lastname: Lo
authors.forename: Christian
authors.initials: C
authors.lastname: Foerch
authors.forename: Rajiv
authors.initials: R
authors.lastname: Gupta
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000009:adverse effects* / Q000494:pharmacology; D000991:Antithrombins / Q000009:adverse effects* / Q000494:pharmacology; D001562:Benzimidazoles / Q000009:adverse effects* / Q000494:pharmacology; D001779:Blood Coagulation Factors / Q000494:pharmacology*; D002543:Cerebral Hemorrhage / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000188:drug therapy; D003287:Contrast Media / Q000494:pharmacology*; D000069604:Dabigatran; D007479:Iopamidol / Q000494:pharmacology*; D008297:Male; D051379:Mice; D015900:Radiography, Dual-Energy Scanned Projection / Q000379:methods*; D013997:Time Factors; D014859:Warfarin / Q000009:adverse effects* / Q000494:pharmacology; D015091:beta-Alanine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000925:Anticoagulants; D000991:Antithrombins; D001562:Benzimidazoles; D001779:Blood Coagulation Factors; D003287:Contrast Media; D015091:beta-Alanine; C025667:prothrombin complex concentrates; D014859:Warfarin; D000069604:Dabigatran; D007479:Iopamidol
keywords: PCC treatment; anticoagulation; contrast extravasation; dabigatran; dual-energy CT; hematoma expansion; intracerebral hemorrhage; warfarin
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