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;44(10):2883-90. doi: 10.1161/STROKEAHA.113.001224. Epub 2013 Aug 6.
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.
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.
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).
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.
脑内出血（ICH）中的对比剂外渗（CE）是持续出血的标志物，也是血肿扩大的预测因子。本研究旨在建立一种可定量评估 CE 的 ICH 模型，分析华法林和达比加群抗凝治疗ICH 时的 CE 特征，并评估凝血酶原复合物浓缩物对与华法林相关 ICH 中 CE 的影响。
CD1 小鼠经口预先给予华法林、达比加群或载体处理。在华法林治疗的亚组小鼠中给予凝血酶原复合物浓缩物。立体定向将 VII 型胶原蛋白酶注入右侧纹状体以诱导 ICH。ICH 诱导后（2-3.5 小时）经静脉注射对比剂（350 μL Isovue 370 mg/mL）。30 分钟后处死小鼠，通过使用双能量 CT 定量血肿中的碘含量来测量 CE。
发现对比剂注射的最佳时间点是 ICH 诱导后 3 小时，这使得使用双能量 CT 可以检测到 CE 的增加和减少。与对照组相比，华法林组的 CE 更高（P=0.002）。达比加群治疗的小鼠与对照组之间的 CE 无显著差异。与未接受治疗的华法林组相比，接受凝血酶原复合物浓缩物治疗的华法林组的 CE 更高（P<0.001）。
双能量 CT 允许定量评估抗凝相关 ICH 模型中作为持续出血标志物的 CE。达比加群引起的 ICH 中的 CE 低于华法林，从而降低了血肿扩大的风险。这构成了达比加群相对于华法林的潜在安全优势。然而，在华法林抗凝的情况下，凝血酶原复合物浓缩物可减少这种副作用。
