Red Cell Survival Following Transfusion in Infants

项目1的主要目标是改善贫血的红细胞(RBC)输注实践， 危重婴儿，接受多次红细胞输注的高危患者组。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大量悬而未决的问题 红细胞输注实践，例如，使用21-42d储存的成人同种异体红细胞(与单独使用新鲜的 RBC&lt；7 d)和使用自体胎盘RBC，这可能是一个更安全的选择，通过护理点使其可行 测试设备。我们的提案扩展了我们之前的PPG的工作，第一次考虑到 婴儿储存对输血后红细胞恢复和存活的影响，考虑到独一无二 以及扰乱RBC存活率测量的关键因素。项目一：S总决赛 假说是异体和自体红细胞在输血后的存活率可以准确地 利用基于生物素标记红细胞的新生羔羊模型对贫血婴儿进行量化 结合数学建模对混杂变量进行普遍补偿 在新生儿早期遇到(例如，由于静脉切开导致的RBC损失，由于 由于贫血和血液增加而产生的红细胞生成引起的输血和红细胞稀释 成交量快速增长)。临床上有用的红细胞恢复和存活参数，我们称之为 “红细胞动力学”(即输血后24小时的短期恢复(“PTR24”)和长期平均值 潜在寿命(“MPL”))将使用我们的 之前的PPG。项目1提出了四个具体目标：1)在成年绵羊身上开发和验证 在高达5个离散密度下生物素化红细胞的能力，以确定多个红细胞的“红细胞动力学” 2)应用目标1中的RBC生物素化方法来测量 应激性红细胞生成对正常成年绵羊稳态红细胞存活率的影响 在新生羔羊中使用来自目标1的RBC生物素化方法来制定一种符合伦理道德的 可接受的、数学上准确的模型，以唯一地补偿上述因素 危重病儿输血后红细胞动力学的影响 在AIMS#1和AIMS#3中验证的生物素化和数学建模方法 测量输注新鲜自体血液的贫血新生儿的输血后红细胞动力学， 新鲜同种异体红细胞和储存的同种异体红细胞。生物素的使用，一种无毒、无放射性的B族维生素， 用流式细胞术同时区分不同的红细胞群体是关键 完成项目一S的目标和与其他红细胞标记方法相比在这两方面都具有明显的优势 安全性和准确性。在利用四个具体目标实现我们的目标时，建立更有效的 通过确定用于贫血婴儿的最佳红细胞输注产品的输血实践， 项目1支持我们的PPG调查机制和优化管理的主题 新生儿贫血。

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.