Erythrocyte contribution to coagulopathy and cerebral oxygenation after intracerebral hemorrhage

项目总结： 脑出血(ICH)是所有卒中亚型中发病率和死亡率最高的，原因是 最初的损伤和持续的出血，也称为血肿扩张(HE)，可能会发生 之后。在高达30%的脑出血患者中，他在24小时内发生急性发作，是导致 在这一患者群体中，结果更差。因此，急性脑出血的治疗模式主要集中在 利用基于快速输血的方法努力改善预后以预防HE。然而，最近 使用凝血因子或血小板的普遍、快速输血治疗方法的试验 预防HE的输血并没有产生改善的结果。这强调了一个关键的知识鸿沟 慢性肝病的治疗途径和治疗靶点。 红细胞(RBC)水平降低与出血有关，已提出的机制是由于 导致血小板的径向位移和内皮结合处于次优状态。而非物质文化遗产中的证据一直 发现低红细胞水平与更差的结果有关，这在很大程度上被归因于受损 脑氧合而不是凝血障碍。这推断出低RBC水平与 蛛网膜下腔出血和创伤性脑损伤的脑氧合功能受损和不良的临床转归 伤害患者群体，因为还没有在ICH中进行这样的研究。然而，有证据表明 基线RBC较低的脑出血患者基础血肿量较大，最近出现HE升高 提示凝血障碍在这些患者中与红细胞水平有关的作用。 红细胞在脑出血后功能性凝血和脑氧合中的作用将通过a) 贫血、脑出血和红细胞输注的简约主义小鼠模型和b)一个预期的观察人 ICH研究评估RBC水平与RBC输注之间的关系 功能性凝血和脑氧合。该项目将填补脑出血治疗方面的一个重要空白。 通过建立新的工具来研究红细胞水平对脑出血预后的影响机制，以期 最终为脑出血患者未来的临床输血治疗方法提供参考，以改善他们的 结果。

PROJECT SUMMARY: Intracerebral hemorrhage (ICH) carries the highest morbidity and mortality of all stroke subtypes due to the initial injury and the ongoing bleeding, otherwise known as hematoma expansion (HE), which can occur afterwards. HE occurs acutely within 24 hours in up to 30% of patients with ICH and is the strongest driver of worse outcomes in this patient population. Consequently, acute ICH treatment paradigms largely focus on preventing HE utilizing rapid transfusion based approaches in efforts to improve outcome. However, recent trials using generalized, rapid transfusion based treatment approaches with coagulation factors or platelet transfusions to prevent HE have not yielded improved outcomes. This emphasizes a critical knowledge gap in approaches and treatment targets of HE. Lower red blood cell (RBC) levels have been associated with bleeding with proposed mechanisms being due to suboptimal radial displacement of platelets and endothelial binding. While evidence in ICH has consistently revealed an association of low RBC levels with worse outcomes, this has largely been attributed to impaired cerebral oxygenation rather than coagulopathy. This extrapolates the associations of low RBC levels with impaired cerebral oxygenation and poor clinical outcomes from subarachnoid hemorrhage and traumatic brain injury patient populations as no such studies have yet been performed in ICH. However, there is evidence of larger baseline hematoma volumes and more recently, increased HE in ICH patients with lower baseline RBC levels to suggest a role of coagulopathy related to RBC levels in these patients. The role of RBCs on functional coagulation and cerebral oxygenation after ICH will be investigated via a) reductionist murine models of anemia, ICH and RBC transfusions and b) a prospective observational human ICH study evaluating the relationship of RBC levels and RBC transfusions on independent changes in functional coagulation and cerebral oxygenation. This project will fill an important gap in ICH treatment paradigms by establishing novel tools to investigate mechanisms of RBC levels on ICH outcomes in order to ultimately inform future clinical transfusion based treatment approaches in patients with ICH to improve their outcomes.