The safety of red blood cell transfusions

红细胞输注的安全性

• 批准号: 8919941
• 负责人: Eldad Arie Hod
• 金额: $ 39.4万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8919941
• 关键词: Acute; Address; Adherence; Adhesions; Adult; Age; Binding; Biological Assay; Blood; Blood Circulation; Childhood; Chronic; Communities; Controlled Study; Cross-Over Studies; Data; Erythrocyte Transfusion; Erythrocytes; Growth; Health; Healthcare; Hemoglobin; Hospitals; Host Defense; Human; In Vitro; Individual; Infection; Iron; Knowledge; Lead; Life; Literature; Medicine; Meta-Analysis; Microbial Biofilms; Modeling; Morbidity - disease rate; New York; Pathogenesis; Patients; Persons; Physiological; Plasma; Presbyterian Church; Production; Retrospective Studies; Risk; Risk Factors; Role; Safety; Sampling; Selection Bias; Serum; Staging; Stream; Surface; Swimming; System; Testing; Therapeutic Embolization; Time; Toxic effect; Transferrin; Transfusion; United States; Virulence Factors; cell injury; clinically relevant; design; extracellular; improved; innovation; macrophage; microbial; microorganism; mortality; pathogen; prevent; trend; uptake

DESCRIPTION (provided by applicant): This project will examine the effect of circulating iron produced from transfusions of older, stored red blood cells (RBCs) on biofilm-related infections. By FDA criteria, RBCs have a maximum refrigerated shelf life of 42 days. Studies suggest that transfusion of "older" versus "fresher" stored RBC units is associated with significantly increased risk of morbidity and mortality. RBCs are damaged progressively during refrigerator storage. After transfusion, storage-damaged RBCs are rapidly cleared from the circulation by macrophages. This RBC hemoglobin iron is then rapidly catabolized and returned to plasma at a pace that can exceed the rate of iron uptake by transferrin, the physiologic iron transporter, and thereby producing circulating non-transferrin- bound iron. Physiologically, virtually all circulating iron is transferrin-bound. In contrast, our human studies show that transfusion of even one unit of stored RBCs can acutely produce circulating non-transferrin-bound iron and enhance bacterial growth in post-transfusion serum samples in vitro. Because iron transport by transferrin is a critical host defense strategy that withholds iron from infectious pathogens, our innovative hypothesis is that release of iron after acute macrophage clearance of storage-damaged RBCs overwhelms the recipient's capacity for safe iron sequestration, thereby producing circulating non- transferrin-bound iron that then acts as a virulence factor by enhancing biofilm formation. Biofilms are aggregates of microorganisms growing in a community embedded in an extracellular polymeric substance. In many microbial systems, differentiation into a biofilm requires high levels of iron. Biofilm-related infections are responsible for importat healthcare-associated infections, such as central line-associated blood stream infections (CLABSI). This proposal will determine the extent to which circulating iron produced by clearance of transfused RBCs enhances biofilm formation of microbial pathogens. Aim #1 will use all pediatric and adult incident cases of CLABSI in our hospital system to conduct an innovative case-crossover and case- time-control retrospective study to determine the extent of the association between the duration of RBC storage prior to transfusion and CLABSI. In Aim #2, we will use static and dynamic in vitro biofilm assays to determine the contribution of non-transferrin-bound iron to biofilm formation of several relevant human pathogens. The current project will fill critical gaps in knowledge by providing evidence for a relationship between transfusions of stored RBCs and CLABSI, and determining the contribution of iron to the underlying mechanism(s) responsible for this effect. This will lead to innovative approaches for preventing production of circulating iron, thereby improving RBC transfusion safety in hospitalized patients.

描述（由申请人提供）：该项目将研究输注较旧的储存红细胞（RBC）产生的循环铁对生物膜相关感染的影响。根据 FDA 标准，红细胞的冷藏保质期最长为 42 天。研究表明，输注“较旧”与“较新鲜”储存的红细胞单位与发病率和死亡率风险显着增加相关。红细胞在冰箱储存过程中会逐渐受损。输血后，储存受损的红细胞会被巨噬细胞迅速从循环中清除。然后，红细胞血红蛋白铁被快速分解代谢并返回血浆，其速度可能超过转铁蛋白（生理性铁转运蛋白）吸收铁的速度，从而产生循环的非转铁蛋白结合铁。从生理学角度来说，几乎所有循环铁都与转铁蛋白结合。相比之下，我们的人体研究表明，即使输注一个单位的储存红细胞，也能迅速产生循环的非转铁蛋白结合铁，并增强体外输血后血清样本中的细菌生长。由于转铁蛋白的铁转运是一种关键的宿主防御策略，可阻止感染性病原体中的铁，因此我们的创新假设是，巨噬细胞急性清除储存受损的红细胞后释放的铁超过了受体安全铁隔离的能力，从而产生循环的非转铁蛋白结合铁，然后通过增强生物膜形成而充当毒力因子。生物膜是生长在嵌入细胞外聚合物的群落中的微生物聚集体。在许多微生物系统中，分化成生物膜需要高水平的铁。生物膜相关感染是重要的医疗保健相关感染的原因，例如中心静脉导管相关血流感染 (CLABSI)。该提案将确定通过清除输入的红细胞产生的循环铁增强微生物病原体生物膜形成的程度。目标#1将使用我们医院系统中所有儿童和成人CLABSI事件病例来进行创新的病例交叉和病例时间对照回顾性研究，以确定输血前红细胞储存时间与CLABSI之间的关联程度。在目标#2中，我们将使用静态和动态体外生物膜测定来确定非转铁蛋白结合铁对几种相关人类病原体生物膜形成的贡献。当前的项目将通过提供储存红细胞输注与 CLABSI 之间关系的证据，并确定铁对造成这种效应的潜在机制的贡献，来填补知识方面的关键空白。这将带来防止循环铁产生的创新方法，从而提高住院患者红细胞输注的安全性。