Abstract WP460: Use of Red Cell Microparticles to Limit Hematoma Growth Following Intracerebral Hemorrhage

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Currently there is no effective treatment for spontaneous intracerebral hemorrhage (sICH). Limiting hematoma extension in sICH is an attractive therapeutic target. Earlier studies demonstrated that red blood cell-derived microparticles (RMP) enhance platelet function and accelerate coagulation, augmenting both primary and secondary hemostasis. In the present study, we determined the efficacy of RMP in reducing hematoma expansion in a rat model of collagenase-induced sICH. RMPs were prepared from human RBCs using a high-pressure extrusion method. At ~24 hours post-collagenase injection, neurological scores were evaluated, rats were sacrificed, and the hematoma areas on images of brain sections were measured. In an earlier study (presented in an abstract form) we determined optimal RMP dose required to lower hematoma growth following sICH. The hematoma volume was lower by 17, 40 (p<0.001 vs placebo group), and 6% in low dose (7.19 x 10 9 particles / kg b.w.), medium dose (2.55 x 10 10 particles / kg b.w.), and high dose (9.48 x 10 10 particles / kg b.w.) treated groups when compared to placebo group, respectively. For those experiments, total RMP dose was delivered over 2 hours using continuous infusion starting 1 h post-collagenase injection. In the present study we evaluated optimal treatment paradigm using optimal protective (medium) dose as identified above. We evaluated the efficacy of RMP when delivered starting at 1 h post-collagenase injection either via four bolus injections (6.375 x 10 9 particles / kg b.w. per injection) 30 min apart (paradigm B) and when delivered using continuous infusion (2.55 x 10 10 particles / kg b.w.) over 1 hour (paradigm C), and compared with when RMP dose was delivered (2.55 x 10 10 particles / kg b.w.) over 2 hours using continuous infusion (paradigm A). We observed that hematoma volume (mm 3 ) for vehicle, and paradigm A, B and C was 71 ± 3 (n = 35), 43 ± 2 (n = 10, p<0.001 vs vehicle), 60 ± 4 (n = 15, p = 0.057 vs vehicle), and 61 ± 4 (n = 15, p = 0.073 vs vehicle), respectively. We observed that neurological score was lower (all p<0.001) in paradigm A (9.3 ± 0.4, n = 10), B (8.7 ± 0.3, n = 15), and C (9.5 ± 0.4, n = 15) groups as compared to placebo group (10.9 ± 0.1, n = 35). Our results indicate that RMPs have potential to lower hematoma growth in sICH patients.