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 preventing hematoma growth. Methods-In C57BL/6 mice receiving DE (4.5 or 9.0 mg/kg), in vivo and in vitro coagulation assays and dabigatran plasma levels were measured repeatedly. Thirty minutes after inducing ICH by striatal collagenase injection, mice received an intravenous injection of saline, prothrombin complex concentrate (PCC; 100 U/kg), murine fresh-frozen plasma (200 L), or recombinant human factor VIIa (8.0 mg/kg). ICH volume was quantified on brain cryosections 24 hours later. Results-DE substantially prolonged tail vein bleeding time and ecarin clotting time for 4 hours corresponding to dabigatran plasma levels. Intracerebral hematoma expansion was observed mainly during the first 3 hours on serial T2* MRI. Anticoagulation with high doses of DE increased the hematoma volume significantly. PCC and, less consistently, fresh-frozen plasma prevented excess hematoma expansion caused by DE, whereas recombinant human factor VIIa was ineffective. Prevention of hematoma growth and reversal of tail vein bleeding time by PCC were dose-dependent. Conclusions-The study provides strong evidence that PCC and, less consistently, fresh-frozen plasma prevent excess intracerebral hematoma expansion in a murine ICH model associated with dabigatran. The efficacy and safety of this strategy must be further evaluated in clinical studies. Key Words: anticoagulation Ⅲ factor VIIa Ⅲ fresh-frozen plasma Ⅲ prothrombin complex concentrate Ⅲ stroke I mproving treatment strategies to prevent stroke in atrial fibrillation (AF) represents a key medical challenge worldwide. Oral anticoagulation (OAC) with vitamin K antagonists reduces the relative stroke risk by Ͼ60%, 1 but vitamin K antagonist have multiple undesirable properties that have resulted in undertreatment of patients at risk. 2 Consequently, new oral anticoagulants have been developed that directly inhibit the key coagulation factors thrombin or factor Xa, respectively. 3 The direct thrombin inhibitor dabigatranetexilate (DE) was recently approved for stroke prevention in AF after the RE-LY trial had shown that DE is not inferior or even superior to warfarin in preventing stroke without compromising bleeding. 4 -6 Although the benefits of OAC outweigh the risk in AF by several fold, 7 intracerebral hemorrhage (ICH) remains the most serious and lethal complication of long-term use of OAC. 8 The mortality for oral anticoagulant-associated ICH (OAC-ICH) is substantially higher than that of spontaneous ICH. 9,10 A major goal of ICH management is to prevent secondary hematoma growth because hematoma size affects outcome after ICH substantially. 11 Current guidelines for managing OAC-IC...

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Background and Purpose— The accuracy of diffusion-weighted imaging (DWI) for the diagnosis of acute cerebral ischemia among patients with suspected ischemic stroke arriving to an emergency room has not been studied in depth. Methods— DWI was performed in 712 patients with acute or subacute focal symptoms that suggested an acute ischemic stroke (AIS), 609 of them with AIS. Results— DWI demonstrated a sensitivity of 90% and specificity of 97%, a positive likelihood ratio of 31 and a negative likelihood ratio of 0.1 for detecting AIS. The overall accuracy was 95%. Of those patients who demonstrated abnormal DWI studies, 99.5% were AIS patients, and of those patients with normal DWI studies 63% were stroke mimics. Conclusions— DWI is accurate in detecting AIS in unselected patients with suspected AIS; a negative study should alert for nonischemic conditions.