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.

项目摘要： 脑内出血（ICH）携带所有中风亚型的发病率和死亡率最高 最初的损伤和正在进行的出血，也称为血肿膨胀（HE），可能发生 然后。他在24小时内急性地发生ICH患者，是 该患者人群的结果更糟。因此，急性ICH治疗范例在很大程度上关注 防止他利用基于快速输血的方法来改善结果。但是，最近 使用具有凝结因子或血小板的广义，快速输血的治疗方法的试验 输血以防止他产生改善的预后。这强调了批判性的知识差距 HE的方法和治疗目标。 较低的红细胞（RBC）水平与提议的机制有关 为血小板和内皮结合的次优位移。虽然ICH中的证据一直持续 揭示了低RBC水平的关联，结果较差，这在很大程度上归因于受损 脑充氧而不是凝血病。这推断了低RBC水平与 蛛网膜下腔出血和创伤性大脑的脑充氧和临床结果不佳 损伤患者人群尚未在ICH中进行此类研究。但是，有证据表明 较大的基线血肿体积，最近，ICH基线rbc的ICH患者的HE增加了 表明这些患者与RBC水平相关的凝血病的作用的水平。 RBC将通过A进行ICH后功能性凝血和脑氧合的作用。 还原主义的贫血，IC​​H和RBC输血的鼠模型以及b）前瞻性观察性人 ICH研究评估了RBC水平和RBC输血与独立变化的关系 功能性凝血和脑充氧。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RBC水平在ICH结果上的机制来范式 最终告知ICH患者的未来基于临床输血的治疗方法，以改善其 结果。