Recombinant Activated Coagulation Factor VII and Prothrombin Complex Concentrates Are Equally Effective in Reducing Hematoma Volume in Experimental Warfarin-Associated Intracerebral Hemorrhage

Background and Purpose-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. Methods-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. Results-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 mu L in the saline group (n=7), 8.6 +/- 4.3 mu L in the rFVIIa group (n=6), and 6.1 +/- 1.8 mu L 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. Conclusions-Our results suggest that PCC and rFVIIa are equally effective in restoring coagulation and preventing excessive hematoma growth in acute warfarin-associated intracerebral hemorrhage. (Stroke. 2012;43:246-249.)