Donor and unit factors associated with recipient RBC alloimmunization formation

与受者红细胞同种免疫形成相关的供者和单位因素

• 批准号: 10515205
• 负责人: Ronald G. Hauser
• 金额: $ 12.56万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10515205
• 关键词: Age; Alloimmunization; Antibodies; Antibody Formation; Antigens; Autoimmunity; Base Ratios; Blood; Blood Banks; Blood Donations; Blood Transfusion; Blood donor; Case-Control Studies; Categories; Characteristics; Chemicals; Communities; Complex Analysis; Cooley' s anemia; Dangerousness; Data; Data Set; Databases; Development; Diagnosis; Disease; Dysmyelopoietic Syndromes; Electronic Health Record; Erythrocyte Transfusion; Erythrocytes; Ethnic Origin; Event; Exposure to; Fetus; Funding; Goals; Health; Hospitals; Human; Incidence; Individual; Inpatients; Institution; Isoantibodies; Link; Modeling; Morbidity - disease rate; Mus; National Heart, Lung, and Blood Institute; Newborn Infant; Odds Ratio; Outcome; Outpatients; Patients; Pregnancy; Prevalence; Public Health; Race; Reaction; Research Design; Risk; Safety; Science; Services; Sickle Cell Anemia; Smoking History; Time; Transfusion; United States; Veins; Whole Blood; antibody detection; case control; cell injury; clinically significant; high risk; innovation; interest; irradiation; mortality; patient population; secondary analysis; sex; time interval

Red blood cell (RBC) alloimmunization is a leading cause of morbidity and mortality in transfusion and pregnancy settings, resulting in hemolytic reactions and other adverse sequelae. Alloimmunization occurs in up to 40% of some patient populations, including those with sickle cell disease (SCD); rates in patients with myelodysplastic syndrome, thalassemia major, and autoimmunity are also high. Most studies of RBC alloimmunization to date have focused on incidence/prevalence rates and recipient characteristics/diagnoses, and few studies have evaluated blood donor or blood unit contributions to RBC alloantibody formation. The National Heart, Lung, and Blood Institute (NHBLI) funded REDS-III vein-to-vein data set, available for public use through BioLINCC, allows a unique opportunity to evaluate RBC alloantibodies in diverse recipients across multiple institutions and to investigate potential blood donor and unit variables involved in transfusion associated alloantibody formation. This data set contains inpatient and outpatient electronic health information from four major blood centers and 12 community and academic hospitals in the United States, over a 4-year time-period from 2013-2017. A query of the data set has shown that there are 651 subjects with a new RBC antibody formed in the time interval (15 days to 16 weeks) following transfusion over which most antibodies would be expected to form. The innovation of the current proposal lies in the unique ability to link blood donor and blood unit characteristics to the recipient outcome of alloimmunization following RBC transfusion. Murine studies have shown that more rapid RBC clearance following transfusion is associated with a higher degree of RBC alloimmunization, regardless of whether that increased clearance is due to longer storage duration or other causes. As such, we hypothesize that factors associated with poorer RBC storage in humans, including red cell storage duration, donor sex, or irradiation, will impact the likelihood of alloantibody formation. We propose to complete a case: control (1:4) study, matching cases and controls for age, sex, diagnosis, race, and ethnicity. With this study design, we propose: Aim 1) To investigate blood donor characteristics associated with RBC alloimmunization in transfusion recipients and Aim 2) To investigate RBC unit characteristics associated with RBC alloimmunization in transfusion recipients. Long term, any blood donor or RBC unit characteristic associated with alloimmunization could be modified for RBC units intended for patients at highest risk of RBC alloimmunization. If new antibody formation could be minimized, transfusion safety will increase.

红细胞（RBC）同种异体免疫是输血中发病和死亡率的主要原因 怀孕环境，导致溶血反应和其他不良后遗症。同种免疫发生 最多40％的患者人群，包括患有镰状细胞病的患者（SCD）；患者的比率 骨髓增生综合征，thalassexya和自身免疫也很高。大多数RBC的研究 迄今 很少有研究评估了对RBC同种抗体形成的献血者或血液单位的贡献。 国家心脏，肺和血液研究所（NHBLI）资助了Reds-III静脉到素食数据集，可用于 通过Biolincc公开使用，允许一个独特的机会来评估RBC同种抗体 在多个机构之间，并研究参与输血的潜在献血者和单位变量 相关的同种抗体形成。该数据集包含住院和门诊电子健康 来自美国四个主要血液中心，12个社区和学术医院的信息 2013 - 2017年为期4年的时间。数据集的查询表明，有651个受试者 输血后，在时间间隔内（15天到16周）形成的RBC抗体大多数 预计将形成抗体。当前提案的创新在于独特的链接能力 rbc后，同种异体免疫的接受者结果的献血者和血单位特征 输血。 鼠研究表明，输血后更快的RBC清除率与较高 RBC的同种异体免疫度，无论清除是否增加是由于存储较长而引起的 持续时间或其他原因。因此，我们假设与RBC存储较差有关的因素 人类，包括红细胞存储持续时间，供体性别或辐照，会影响同种抗体的可能性 形成。我们建议完成一个案例：对照（1：4）研究，匹配案例和年龄，性别的对照 诊断，种族和种族。通过这项研究设计，我们建议：目标1）调查献血者 与输血受体中的RBC同种异体免疫相关的特征和目标2）研究RBC 与输血接受者中的RBC同种免疫相关的单位特征。 长期，可以修改与同种异体免疫相关的任何献血者或RBC单位特征 RBC单位适用于RBC同种免疫风险最高的患者。如果新的抗体形成可能是 最小化的输血安全将增加。