Red Cell Survival Following Transfusion in Infants

婴儿输血后红细胞的存活率

• 批准号: 7217657
• 负责人: JOHN Andrew WIDNESS
• 金额: $ 49.86万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7217657
• 关键词: anemia; autologous transplantation; biotin; biotinylation; blood transfusion; cell age; cell population study; cell senescence; disease /disorder model; erythrocytes; erythropoiesis; flow cytometry; homologous transplantation; human subject; mathematical model; newborn animals; newborn human (0-6 weeks); premature infant human; sheep; stress

The primary goal of Project 1 is to improve red blood cell (RBC) transfusion practices for anemic, critically ill infants, a high-risk patient group given multiple RBC transfusions. The newborn infant and lamb studies proposed are timely because they address substantive unresolved issues in neonatal RBC transfusion practices, e.g., use of 21-42 d stored adult allogeneic RBCs (vs. exclusive use of fresh RBCs <7 d) and use of autologous placental RBCs, potentially a safer option made feasible by point-ofcare testing devices. Our proposal extends our previous PPG's work by considering for the first time in infants the effect of storage on RBC post-transfusion recovery and survival, taking into account unique and critical factors that perturb, thereby confounding, RBC survival measurements. Project 1's overall hypothesis is that post-transfusion survival of allogeneic and autologous erythrocytes can be accurately quantified in anemic human infants using a newborn lamb model based on biotin-labeled RBCs combined with mathematical modeling to compensate for confounding variables commonly encountered in the early newborn period (e.g., RBC loss due to phlebotomy, RBC gain due to transfusion, and RBC dilution due to erythropoiesis both in response to anemia and to increased blood volume with rapid growth). Clinically useful RBC recovery and survival parameters, which we refer to as "RBC kinetics" (i.e., short-term post-transfusion recovery at 24 hr ("PTR24") and long-term mean potential life span ("MPL")) will be determined using RBC biotinylation methodologies developed in our previous PPG. Project 1 proposes, in four specific aims, to: 1) develop and validate in adult sheep the ability to biotinylate RBCs at up to 5 discrete densities to determine "RBC kinetics" of multiple RBC populations simultaneously; 2) apply the RBC biotinylation methodology from Aim #1 to measure the effect of stress erythropoiesis on RBC survival in normal adult sheep in steady-state erythropoiesis; 3) utilize in newborn lambs the RBC biotinylation methodology from Aim #1 to develop an ethically acceptable, mathematically accurate model to compensate for the above-noted factors uniquely influencing measurements of posttransfusion RBC Kinetics in critically ill infants; and 4) use the RBC biotinylation and mathematical modeling methodologies validated in Aims #1 and #3 to accurately measure post-transfusion RBC kinetics in anemic newborn infants transfused with fresh autologous, fresh allogeneic and stored allogeneic RBCs. The use of biotin, a non-toxic, non- radioactive B vitamin, to distinguish among different RBC populations simultaneously by flow cytometry is critical for accomplishing Project 1's aims and holds clear advantages over other RBC labeling methods in both safety and accuracy. In utilizing the four Specific Aims to achieve our goal of establishing more effective transfusion practices by identifying the optimal RBC transfusion product for use in anemic infants, Project 1 supports our PPG's themes of investigating the mechanisms and optimizing the management of neonatal anemia.

项目1的主要目标是改善贫血的红细胞（RBC）输血实践， 重病的婴儿，一个高危患者组，分别输注了多次RBC。新生婴儿和 提出的羔羊研究是及时的，因为它们解决了新生儿中实质性未解决的问题 RBC输血实践，例如，使用21-42 d存储的成人同种异体RBC（相对于独家使用新鲜 RBC <7 d）和自体胎盘RBC的使用，这可能是可行的可行选择 测试设备。我们的建议首次考虑在 婴儿考虑到独特 以及扰乱的关键因素，因此，RBC生存测量值。项目1的整体 假设是同种异体和自taulogus红细胞的转移后灌注存活率可以准确 使用基于生物素标记的RBC的新生羔羊模型在贫血的人类婴儿中量化 与数学建模相结合以补偿通常的混杂变量 在新生儿早期遇到（例如，由于静脉切开术引起的RBC损失，RBC的增益 输血，以及由于贫血而引起的红细胞生成引起的RBC稀释，并增加了血液 体积随着快速增长）。临床上有用的RBC恢复和生存参数，我们称为 “ RBC动力学”（即24小时（“ PTR24”）和长期平均值的短期输血后恢复 潜在的寿命（“ MPL”）将使用我们在我们的RBC生物素化方法中确定 以前的ppg。项目1在四个具体目标中提出：1）在成年绵羊中发展和验证 能够以多达5个离散密度生物素化RBC确定多个RBC的“ RBC动力学” 人口同时； 2）从目标1应用RBC生物素化方法来测量 稳态促红细胞生成的正常成年绵羊RBC生存的胁迫性红细胞生存的影响； 3） 利用新生羔羊的RBC生物素化方法从AIM＃1进行道德发展 可以接受，数学准确的模型，以弥补上述因素的独特因素 影响重症婴儿中输血后RBC动力学的测量； 4）使用RBC 在目标＃1和＃3中验证的生物素化和数学建模方法准确 在贫血的新生婴儿中测量输血后的RBC动力学 新鲜的同种异体和储存的同种异体RBC。生物素的使用，一种无毒的，非放射性B维生素， 通过流式细胞术同时区分不同的RBC种群对于 完成项目1的目标并具有与其他RBC标签方法相比的明确优势 安全性和准确性。利用四个特定目标来实现我们的目标，以建立更有效的目标 通过识别用于贫血婴儿的最佳RBC输血产品，通过输血做法 项目1支持我们PPG调查机制和优化管理的主题 新生儿贫血。