title: Rapid reversal of anticoagulation reduces hemorrhage volume in a mouse model of warfarin-associated intracerebral hemorrhage.
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 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.
authors.affiliation: Neuroprotection Research Laboratory, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA. foerch@em.uni-frankfurt.de
authors.forename: Christian
authors.initials: C
authors.lastname: Foerch
authors.forename: Ken
authors.initials: K
authors.lastname: Arai
authors.forename: Elizabeth Merrill
authors.initials: EM
authors.lastname: Van Cott
authors.forename: Klaus
authors.initials: K
authors.lastname: van Leyen
authors.forename: Eng H
authors.initials: EH
authors.lastname: Lo