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: 8534320
• 负责人: John D Roback
• 金额: $ 18.66万
• 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/8534320
• 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）： 这是针对RFA-HL-08-005（优先分数= 191）提交的修订申请。最近的证据表明，红细胞（RBC）与内皮细胞协同作用以调节组织血流。两种RBC（是局部O2需求的精细调整传感器）和内皮细胞释放介体，包括控制血管张力的一氧化氮（NO），从而使血流和O2递送。临床研究表明，RBC输血与受体的发病率和死亡率有关，并且这些事件在统计学上与使用“老化” RBC单位和增加输血体积有关。但是，这些事件及其表现形式的发生是可变的，这使研究它们的努力感到困惑。我们假设在FDA批准的血库条件下存储的捐赠的RBC降低了无合成和/或没有增加清除活动的能力，这两者都导致血管床中没有水平降低。此外，其他因素的集合（减少了2,3 DPG；内皮功能障碍；转移后血细胞比容水平升高）可能会进一步降低没有生物利用度，导致血管收缩，减少血液流量和减少组织O2的递送。没有足够的无生物利用度（INOBA）的假设汇集了先前未连接的数据，以提出一种在RBC输血接受者中与RBC单位和受体特异性因素联系起来的常见病理生理机制。该假设不仅说明了RBC输血后不良事件的可变性，而且还导致了许多易于测试的预测，这些预测将在AIMS 1-3中使用人类输血接受者进行详细分析。 公共卫生相关性： 红细胞输血代表了贫血患者的救生疗法。但是，输血与不良反应有关。这些研究将寻求确定为什么在输血后发生不良后果，并开发改善血液收集和储存的方法以最大程度地减少这些结果。