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Foerch C, Arai K, Van Cott EM, van Leyen K, Lo EH: Rapid reversal of anticoagulation reduces hemorrhage volume in a mouse model of warfarin-associated intracerebral hemorrhage. J Cereb Blood Flow Metab. 2009 May;29(5):1015-21. Epub 2009 Mar 25.
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 i.v. (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 microL) compared with saline controls (15.3+/-11.2 microL, P=0.015). In the saline group, 45% of the mice developed large hematomas (i.e., > 15 microL). 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. |
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