Erythrocyte contribution to coagulopathy and cerebral oxygenation after intracerebral hemorrhage

红细胞对脑出血后凝血障碍和脑氧合的贡献

• 批准号: 10472458
• 负责人: David Roh
• 金额: $ 19.06万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10472458
• 关键词: Activated Partial Thromboplastin Time measurement; Acute; Admission activity; Affect; Anemia; Animal Experimentation; Animals; Antifibrinolytic Agents; Back; Binding; Blood Coagulation Disorders; Blood Coagulation Factor; Blood Platelets; Blood Tests; Blood coagulation; Brain; Cerebral Hypoxia; Cerebral hemisphere hemorrhage; Cerebrum; Cessation of life; Clinical; Clinical Trials; Coagulation Process; Data; Endothelium; Erythrocyte Transfusion; Erythrocytes; Fibrinogen; Future; Hematoma; Hemorrhage; Hemostatic function; Hour; Human; Impairment; Injury; Knowledge; Literature; Measures; Mediating; Methodological Studies; Monitor; Morbidity - disease rate; Observational Study; Outcome; Oxygen; Patient-Focused Outcomes; Patients; Plasma; Platelet Count measurement; Platelet Transfusion; Play; Prothrombin time assay; Radial; Research; Risk; Risk Factors; Role; Rotation; Scalp structure; Stroke; Subarachnoid Hemorrhage; Testing; Thrombelastography; Tissues; Training; Transfusion; Traumatic Brain Injury; Venous; Whole Blood; base; bench to bedside; cerebral oxygenation; clinically relevant; disability; human study; improved; improved outcome; innovation; insight; interstitial; mortality; mouse model; novel; patient population; prevent; prospective; stroke patient; tissue oxygenation; tool; translational scientist

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.

项目概要： 脑出血 (ICH) 在所有卒中亚型中发病率和死亡率最高，原因是 初始损伤和持续出血，也称为血肿扩张 (HE)，可能会发生 然后。高达 30% 的 ICH 患者会在 24 小时内急性发生 HE，并且是最强烈的驱动因素 该患者群体的结果更糟。因此，急性脑出血治疗范式主要集中于 利用基于快速输血的方法来预防 HE，以努力改善结果。然而，最近 使用基于凝血因子或血小板的通用快速输血治疗方法的试验 预防 HE 的输血并未取得改善的结果。这强调了关键的知识差距 HE的治疗方法和目标。 较低的红细胞 (RBC) 水平与出血有关，其机制如下 血小板和内皮结合的次优径向位移。虽然 ICH 中的证据一致 揭示了低红细胞水平与较差结果的关联，这很大程度上归因于受损 脑氧合而不是凝血障碍。这推断低红细胞水平与 蛛网膜下腔出血和脑外伤导致脑氧合受损和临床结果不佳 伤害患者群体，因为尚未在 ICH 中进行此类研究。然而，有证据表明 基线红细胞较低的 ICH 患者基线血肿量较大，最近 HE 增加 水平表明凝血障碍与这些患者的红细胞水平相关。 ICH后红细胞对功能性凝血和脑氧合的作用将通过a)进行研究 贫血、ICH 和红细胞输血的还原论小鼠模型和 b) 前瞻性观察人类 ICH 研究评估红细胞水平和红细胞输注与独立变化之间的关系 功能性凝血和脑氧合。该项目将填补ICH治疗的重要空白 通过建立新的工具来研究红细胞水平对 ICH 结果的影响机制，从而建立新的范式 最终为脑出血患者未来基于输血的临床治疗方法提供信息，以改善他们的病情 结果。