Adverse effects of RBC transfusions: A unifying hypothesis

红细胞输注的不良反应：统一假设

• 批准号: 8294549
• 负责人: John D Roback
• 金额: $ 33.71万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-17 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8294549
• 关键词: Accounting; Adverse effects; Adverse event; Age; Biochemical; Biological Assay; Biological Availability; Biological Markers; Blood; Blood Banks; Blood Vessels; Blood capillaries; Blood flow; Carbon Dioxide; Cardiovascular Diseases; Cell Volumes; Cellular Structures; Clinical; Clinical Research; Collection; Data; Data Set; Defect; Electron Spin Resonance Spectroscopy; Endothelial Cells; Erythrocyte Transfusion; Erythrocytes; Event; Exercise; FDA approved; Fluorometry; Functional disorder; Hematocrit procedure; Hemoglobin; Human; In Vitro; Individual; Laboratories; Lead; Lesion; Link; Mediating; Mediator of activation protein; Methods; Microcirculation; Modeling; Modification; Monitor; Morbidity - disease rate; Nitric Oxide; Organ; Outcome; Oxygen; Patients; Perfusion; Physiological; Play; Predictive Factor; Process; Production; Public Health; Rattus; Rejuvenation; Risk; Role; Screening procedure; System; Testing; Time; Tissues; Transfusion; Ultrasonography; Vasodilation; Work; adverse outcome; aged; arteriole; capillary; healthy volunteer; improved; in vivo; irradiation; mortality; novel; prevent; public health relevance; remediation; response; sensor; tissue oxygenation; vascular bed; vasoconstriction; venule

DESCRIPTION (provided by applicant): This is a revised application submitted in response to RFA-HL-08-005 (Priority score = 191). Recent evidence suggests that red blood cells (RBCs) work in concert with endothelial cells to regulate tissue blood flow. Both RBCs (which are finely-tuned sensors of local O2 demand) and endothelial cells release mediators including nitric oxide (NO) that control vascular tone and thus blood flow and O2 delivery. Clinical studies suggest that RBC transfusions are associated with morbidity and mortality in recipients, and that these events are statistically associated with the use of "aged" RBC units and increased transfusion volumes. However, the occurrence of these events and their manifestations are variable, which has confounded efforts to study them. We hypothesize that donated RBCs stored under FDA-approved blood bank conditions have reduced capacity for NO synthesis and/or increased NO scavenging activity, both leading to reduced NO levels in vascular beds. Furthermore, a collection of other factors (reduced 2,3 DPG; endothelial dysfunction; elevated post-transfusion hematocrit levels) may further reduce NO bioavailability, leading to vasoconstriction, decreased blood flow, and reduced tissue O2 delivery. This hypothesis of insufficient NO bioavailability (INOBA) brings together previously unconnected data to suggest a common pathophysiologic mechanism linking RBC unit- and recipient-specific factors in the occurrence of morbidity/mortality in RBC transfusion recipients. This hypothesis not only accounts for the variability of adverse events following RBC transfusion, but also leads to a number of readily testable predictions that will be investigated in Aims 1-3 using detailed analyses of human transfusion recipients. PUBLIC HEALTH RELEVANCE: Red blood cell transfusions represent lifesaving therapies for anemic patients. However, transfusions are associated with adverse effects. These studies will seek to determine why adverse outcomes happen after transfusion, and develop ways to improve blood collection and storage to minimize these outcomes.

描述（由申请人提供）： 这是根据 RFA-HL-08-005 提交的修订申请（优先级评分 = 191）。最近的证据表明，红细胞 (RBC) 与内皮细胞协同调节组织血流。红细胞（局部 O2 需求的微调传感器）和内皮细胞都会释放包括一氧化氮 (NO) 在内的介质，控制血管张力，从而控制血流和 O2 输送。临床研究表明，红细胞输注与受者的发病率和死亡率相关，并且这些事件在统计上与使用“老化”红细胞单位和增加输血量相关。然而，这些事件的发生及其表现形式各不相同，这使得研究它们的努力变得混乱。我们假设，在 FDA 批准的血库条件下储存的捐赠红细胞会降低 NO 合成能力和/或增加 NO 清除活性，从而导致血管床中 NO 水平降低。此外，一系列其他因素（2,3 DPG 减少、内皮功能障碍、输血后血细胞比容水平升高）可能进一步降低 NO 生物利用度，导致血管收缩、血流量减少和组织 O2 输送减少。这种一氧化氮生物利用度不足的假设 (INOBA) 汇集了以前未关联的数据，提出了一种常见的病理生理机制，该机制将红细胞单位和接受者特异性因素与红细胞输血受者发病/死亡的发生联系起来。这一假设不仅解释了红细胞输血后不良事件的变异性，而且还导致了许多易于测试的预测，这些预测将在目标 1-3 中使用对人类输血受者的详细分析进行研究。 公共卫生相关性： 红细胞输注代表了贫血患者的救命疗法。然而，输血会带来不良反应。这些研究将试图确定为什么输血后会发生不良后果，并开发改进血液采集和储存的方法，以尽量减少这些后果。