Rapid Reversal of Anticoagulation Reduces Hemorrhage Volume in a Mouse Model of Warfarin-Associated Intracerebral Hemorrhage
Open Access
- 25 March 2009
- journal article
- Published by SAGE Publications in Journal of Cerebral Blood Flow & Metabolism
- Vol. 29 (5) , 1015-1021
- https://doi.org/10.1038/jcbfm.2009.27
Abstract
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 μL) compared with saline controls (15.3 ± 11.2 μL, P = 0.015). In the saline group, 45% of the mice developed large hematomas (i.e., > 15 μL). 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.Keywords
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