Rapid reversal of anticoagulation reduces hemorrhage volume in a mouse model of Warfarin-associated intracerebral hemorrhage
Rapid reversal of anticoagulation reduces hemorrhage volume in a mouse model of Warfarin-associated intracerebral hemorrhage
复制标题
DOI：
10.1038/jcbfm.2009.27
复制
发表时间：
2009-05-01
影响因子：
6.3
通讯作者：
Lo, Eng H.
中科院分区：
文献类型：
--
作者：
Foerch, Christian;Arai, Ken;Lo, Eng H.
华法林相关性脑出血（W-ICH）是一种严重类型的卒中。对于W-ICH的最佳治疗方法尚无共识。使用小鼠模型，我们测试了使用人凝血酶原复合物浓缩物（PCC）快速逆转抗凝是否可以减少出血量。雄性CD-1小鼠用华法林（2 mg/kg，24小时）处理，得到平均（+/- s.d.）国际标准化比率为3.5 +/- 0.9。首先，我们发现静脉注射人PCC可以迅速逆转小鼠的抗凝作用。第二，立体定向注射胶原酶诱导右侧纹状体出血。45分钟后，动物随机接受PCC（100 U/kg）或生理盐水IV给药（每组n = 12）。出血诱导后24小时，使用血红蛋白光度测定法定量出血量。与生理盐水对照组（15.3 +/- 11.2 μ L，P = 0.015）相比，PCC治疗组动物的平均出血量（6.5 +/- 3.1 μ L）减少。在盐水组中，45%的小鼠出现大血肿（即，> 15 μ L）。相反，在PCC组中从未发现如此广泛的病变。我们提供的实验数据表明，PCC是一种有效的急性治疗W-ICH方面减少出血量。未来的研究需要评估我们发现的人类W-ICH的治疗潜力。脑血流与代谢杂志（2009）29，1015-1021; doi：10.1038/jcbfm.2009.27; 2009年3月25日在线发表
Warfarin-associated intracerebral hemorrhage (W-ICH) is a severe type of stroke. There is no consensus on the optimal treatment for W-ICH. Using a mouse model, we tested whether the rapid reversal of anticoagulation using human prothrombin complex concentrate (PCC) can reduce hemorrhagic blood volume. Male CD-1 mice were treated with warfarin (2 mg/kg over 24 h), resulting in a mean (+/- s.d.) International Normalized Ratio of 3.5 +/- 0.9. First, we showed that an intravenous administration of human PCC rapidly reversed anticoagulation in mice. Second, a stereotactic injection of collagenase was administered to induce hemorrhage in the right striatum. Forty-five minutes later, the animals were randomly treated with PCC (100 U/kg) or saline IV (n = 12 per group). Twenty-four hours after hemorrhage induction, hemorrhagic blood volume was quantified using a photometric hemoglobin assay. The mean hemorrhagic blood volume was reduced in PCC-treated animals (6.5 +/- 3.1 mu L) compared with saline controls (15.3 +/- 11.2 mu L, P = 0.015). In the saline group, 45% of the mice developed large hematomas (i.e., > 15 mu L). In contrast, such extensive lesions were never found in the PCC group. We provide experimental data suggesting PCC to be an effective acute treatment for W-ICH in terms of reducing hemorrhagic blood volume. Future studies are needed to assess the therapeutic potential emerging from our finding for human W-ICH. Journal of Cerebral Blood Flow & Metabolism (2009) 29, 1015-1021; doi:10.1038/jcbfm.2009.27; published online 25 March 2009