Department of Neurology, Goethe-University, Schleusenweg 2-16, 60528 Frankfurt am Main, Germany.
Stroke. 2012 Jan;43(1):246-9. doi: 10.1161/STROKEAHA.111.629360. Epub 2011 Oct 13.
Based on an experimental model of warfarin-associated intracerebral hemorrhage, we investigated whether the rapid reversal of anticoagulation using prothrombin complex concentrates (PCC) or recombinant activated coagulation factor VII (rFVIIa) reduces hematoma volume.
Mice were orally pretreated with warfarin (2 mg/kg). Intracerebral hemorrhage was induced by collagenase injection into the right striatum. Forty-five minutes later, PCC (100 IE/kg), rFVIIa (1 mg/kg), or an equal volume of saline was administered intravenously. Hematoma volume after 24 hours was quantified using a photometric hemoglobin assay.
International normalized ratio was 4.3±0.4 in saline-treated mice, 0.9±0.1 in rFVIIa mice, and 1.4±0.2 in PCC mice. Intracerebral hemorrhage volume was 29.0±19.7 μL in the saline group (n=7), 8.6±4.3 μL in the rFVIIa group (n=6), and 6.1±1.8 μL in the PCC group (n=7; analysis of variance between-group differences P=0.004; post hoc rFVIIa versus saline P=0.021; PCC versus saline P=0.007). No significant difference was found between PCC- and rFVIIa-treated animals.
Our results suggest that PCC and rFVIIa are equally effective in restoring coagulation and preventing excessive hematoma growth in acute warfarin-associated intracerebral hemorrhage.
基于华法林相关性脑出血的实验模型，我们研究了使用凝血酶原复合物浓缩物（PCC）或重组活化凝血因子 VII（rFVIIa）快速逆转抗凝是否能减少血肿体积。
小鼠经口给予华法林（2mg/kg）预处理。通过将胶原酶注入右侧纹状体诱导脑出血。45 分钟后，静脉内给予 PCC（100IE/kg）、rFVIIa（1mg/kg）或等量生理盐水。使用比色法血红蛋白测定法在 24 小时后定量血肿体积。
在生理盐水处理的小鼠中，国际标准化比值为 4.3±0.4，rFVIIa 小鼠为 0.9±0.1，PCC 小鼠为 1.4±0.2。在生理盐水组（n=7）、rFVIIa 组（n=6）和 PCC 组（n=7）中，脑出血体积分别为 29.0±19.7μL、8.6±4.3μL 和 6.1±1.8μL。组间差异的方差分析 P=0.004；rFVIIa 与生理盐水相比 P=0.021；PCC 与生理盐水相比 P=0.007。PCC 和 rFVIIa 治疗的动物之间未发现显著差异。
我们的结果表明，PCC 和 rFVIIa 在恢复凝血和预防急性华法林相关性脑出血中过量血肿增长方面同样有效。
