Introduction: Severe anemia causes hematoma expansion (HE) after intracerebral hemorrhage (ICH) in murine models. It is unclear whether mild anemia impacts HE and whether red blood cell (RBC) transfusions improve these outcomes. We hypothesized that mild anemia causes HE and RBC infusions improve these outcomes. Given that RBC transfusion efficacy may be impacted by donor characteristics, we explored whether donor sex or age impacted outcomes. Methods: Mild anemia was induced in 26 8-week-old C57/BL6 mice via iron-deficient chow. RBC infusion units were created via separate colonies of male and female C57/BL6 mice, ranging from 7-27 weeks old. Anemic mice were randomized to receive 800 uL at 60% hematocrit fresh RBC vs sham saline infusions intraperitoneally prior to collagenase ICH induction, with hemoglobin (Hb) concentrations verified post-infusion using Drabkin’s assay. ICH volume and HE were quantified using serial T2-weighed MRI at 1, 4, and 24 hours after ICH. Correlations of Hb concentrations with ICH volume and HE were assessed. Intergroup differences of radiographic outcomes between RBC-infused and non-infused animals were assessed using non-parametric Mann-Whitney U tests. Subgroup analyses were performed amongst RBC-infused animals to examine whether donor sex or age impacted radiographic outcomes and post-infusion Hb recoveries. Results: RBC infusion resulted in higher Hb concentrations compared to sham-treated anemic mice (18.7g/dL vs 12.5g/dL; p<0.001). We identified inverse correlations of lower Hb with larger final ICH volume (rho: -0.42; p=0.04) and HE (rho: -0.47; p=0.02). Trends toward less HE in RBC-infused ICH mice were seen compared to non-infused animals (0.5mm3 vs 2.1mm3; p=0.06). No significant differences in final ICH volume were seen (4.3mm3 vs 5.4mm3; p=0.35). Among RBC-infused animals only, mice receiving infusions from female donors trended toward lower post-transfusion Hb recoveries (16.9g/dL vs 19.2g/dL; p=0.06). Separately, infusions from older donors correlated with increased Hb recoveries (sigma: 0.9; p=0.001). These RBC-infusion characteristics did not relate to ICH volumes or HE. Conclusions: In mildly anemic mice, lower Hb concentrations associated with larger lesion volume and greater HE after ICH. While RBC transfusions may abrogate HE burden in this setting, further work is required to verify these findings and assess whether certain transfusion characteristics can optimize treatment effects.
Fliginger et al. (Thu,) studied this question.