Erythrocyte contribution to coagulopathy and cerebral oxygenation after intracerebral hemorrhage

项目概要： 脑出血（ICH）是所有卒中亚型中发病率和死亡率最高的， 初始损伤和持续出血，也称为血肿扩大（HE），可能发生 事后在高达30%的ICH患者中，HE在24小时内急性发生，并且是ICH的最强驱动因素。 这一患者人群的预后更差。因此，急性ICH治疗模式主要集中在 利用基于快速输血的方法预防HE，努力改善结局。但最近的 使用广泛的、基于快速输血的凝血因子或血小板治疗方法的试验 输血预防肝性脑病并没有产生改善的结果。这突出表明， 肝性脑病的治疗途径和治疗目标。 较低的红细胞（RBC）水平与出血有关， 血小板和内皮结合的次优径向位移。虽然ICH中的证据一直 揭示了低RBC水平与更差结果的相关性，这在很大程度上归因于受损 脑氧合而不是凝血功能障碍。这推断了低RBC水平与 蛛网膜下腔出血和脑外伤导致的脑氧合受损和临床结局不良 由于尚未在ICH中进行此类研究，因此，然而，有证据表明， 在基线RBC较低的ICH患者中，基线血肿体积较大，最近HE增加 水平，以表明这些患者中与RBC水平相关的凝血病的作用。 将通过以下方式研究RBC在ICH后功能性凝血和脑氧合中的作用：a） 贫血、ICH和RBC输注的还原论小鼠模型和B）前瞻性观察人类 ICH研究，评价RBC水平和RBC输注对独立变化的关系， 功能性凝血和脑氧合。该项目将填补ICH治疗的一个重要空白 通过建立新的工具来研究RBC水平对ICH结局的机制， 最终为ICH患者未来基于输血的临床治疗方法提供信息， 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.