Stroke Anticoagulation With the Oral Direct Thrombin Inhibitor Dabigatran Does Not Enlarge Hematoma Volume in Experimental Intracerebral Hemorrhage
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چکیده
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. Methods and 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 L in controls, 4.8 2.7 L in DE mice, and 14.5 11.8 L 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. (Circulation. 2011;124:1654-1662.)
منابع مشابه
Anticoagulation with the oral direct thrombin inhibitor dabigatran does not enlarge hematoma volume in experimental intracerebral hemorrhage.
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...
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Little is known about the pathophysiology of intracerebral haemorrhage that occurs during anticoagulant treatment. In observational studies, investigators have reported larger haematoma volumes and worse functional outcome in these patients than in those with intracerebral haemorrhage and a normal coagulation status. The need to prevent extensive haematoma enlargement by rapid reversal of the a...
متن کاملHemostatic therapy in experimental intracerebral hemorrhage associated with the direct thrombin inhibitor dabigatran.
BACKGROUND AND PURPOSE Dabigatran-etexilate (DE) recently has been approved for stroke prevention in atrial fibrillation. However, lack of effective antagonists represents a major concern in the event of intracerebral hemorrhage (ICH). The aims of the present study were to establish a murine model of ICH associated with dabigatran, and to test the efficacy of different hemostatic factors in pre...
متن کاملLetter by Moll regarding article, "Hemostatic therapy in experimental intracerebral hemorrhage associated with the direct thrombin inhibitor dabigatran".
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Secondary intracerebral hemorrhage due to early initiation of oral anticoagulation after ischemic stroke: an experimental study in mice.
BACKGROUND AND PURPOSE The uncertain risk of secondary intracerebral hemorrhage (sICH) frequently keeps clinicians from initiating oral anticoagulation (OAC) early after ischemic cardioembolic stroke. The goal of this experimental study was to determine the risk of sICH depending on the timing of OAC initiation relative to stroke onset and to address the role of hematogenous macrophages for rep...
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تاریخ انتشار 2011