Early hemostatic therapy using recombinant factor VIIa in a collagenase-induced intracerebral hemorrhage model in rats

Abstract

Neurological deterioration during the first day after intracerebral hemorrhage (ICH) is associated with early hematoma growth in 18 to 38% of patients. While clinical studies continue to evaluate efficacy of activated recombinant factor VII (rFVIIa) for reducing frequency of early hematoma growth, there have been no studies investigating the effect of rFVIIa on early hematoma growth. We used a collagenase-induced ICH model in the rat to evaluate the effects of rFVIIa on early hematoma growth. Two hours after injection of 0.14 U of type IV bacterial collagenase in 10 μL of saline into the basal ganglia, a small amount of blood collected in the striatum. The ICH gradually increased in size, extending posteriorly to the thalamus by 24 hours after injection. Intravenous administration of rFVIIa immediately after collagenase injection decreased average hematoma volume at 24 hours compared with vehicle-treated group (168.1 ± 13.4 mm3 vs. 118.3 ± 23.0 mm3, p < 0:01). There was also a decrease in total hemoglobin content in rats treated with rFVIIa compared with vehicletreated rats (optical density at 550 nm: 0.87 ± 0.08 vs. 0.71 ± 0.09, p < 0:05). There was no difference in cortical brain water content overlying the hematoma between the rFVIIa- and vehicle-treated groups (81.4 ± 0.7% vs. 81.7 ± 0.4%). Our study indicates that treatment with rFVIIa may be useful in reducing the frequency of early hematoma growth in ICH patients. © 2006 Springer-Verlag.