• Sae-Yeon Won, Frieder Schlunk, Julien Dinkel, Hulya Karatas, Wendy Leung, Kazuhide Hayakawa, Arne Lauer, Helmuth Steinmetz, Eng H Lo, Christian Foerch, and Rajiv Gupta.
• 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.).
• Stroke. 2013 Oct 1; 44 (10): 2883-90.

Background And PurposeContrast 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.MethodsCD1-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.ResultsThe 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).ConclusionsDual-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.

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