Point-of-Care RBC Washing to Prevent Transfusion-Related Pulmonary Complications

描述(申请人提供)：与输血相关的呼吸道并发症、与输血相关的急性肺损伤(TRALI)和与输血相关的循环过载(TACO)是与输血相关的死亡的主要原因。目前，没有有效的策略来预防输注红细胞(RBC)后的这些并发症。尽管导致这些并发症的机制仍不完全清楚，但存在于RBC储存溶液中的可溶性生物反应调节剂(BRM)被认为起着重要作用。在输血前对异体红细胞进行护理点清洗可以去除这些BRM，从而减轻它们对术后呼吸道并发症的影响。我们的长期目标是开发能够预防TRALI和TACO的有效策略。这项建议的目的是评估使用FDA批准的自体输血系统对异基因白细胞减少(LR)红细胞进行护理点清洗的可行性、安全性、有效性和临床影响。我们将具体评估这种干预对接受高危心脏手术的患者输血相关呼吸道并发症的中间标记物的影响。我们的进一步目标是更好地了解这些并发症背后的机制。为了实现这些目标，本应用程序提出了以下具体目标。目标1：确定护理点的可行性、安全性和有效性 连续自体输血系统(CATS)在成人心脏手术患者输注同种异体LR-RBC中的应用目的2：证明与标准发行的同种异体LR-红细胞相比，同种异体LR-RBC的护理点清洗对RBC输注的受者反应的影响程度。目的3：评价同种异体异基因LR-RBC护理点洗对受者临床结局的影响。为了实现这些目标，我们提出了一项多中心I/II期随机临床试验。接受异基因LR-RBC输注的成人心脏手术患者将在手术当天随机接受护理点、使用CATS设备清洗的红细胞或标准发行的红细胞。将使用经过验证的风险预测模型来促进本次试验的定向登记。这项提案涉及这一筹资机会公告中的多个重点主题，包括但不限于：1)输血的非传染性并发症，包括TRALI；2)输血成分的免疫调节、炎症和血管调节特性；以及3)评估推出新的血液产品制剂或输血策略对输血相关不良事件和接受者的临床结果的影响。

DESCRIPTION (provided by applicant): The transfusion-related respiratory complications transfusion-related acute lung injury (TRALI) and transfusion- associated circulatory overload (TACO) are leading causes of transfusion-related death. At present, there are no effective strategies for the prevention of these complications following red blood cell (RBC) transfusion. Although the mechanisms that underlie these complications remain incompletely defined, soluble biological response modifiers (BRMs) residing within the RBC storage solution are believed to play an important role. Point-of-care washing of allogeneic RBCs prior to transfusion may remove these BRMs, thereby mitigating their impact on postoperative respiratory complications. Our long-range goals are to develop effective strategies that can prevent TRALI and TACO. The objective of this proposal is to evaluate the feasibility, safety, efficacy, and clinical impact of point-of-care washing for allogeneic leukocyte-reduced (LR) RBCs using an FDA-approved autotransfusion system. We will specifically evaluate the impact of this intervention on intermediate markers of transfusion-related respiratory complications in patients undergoing high-risk cardiac surgery. We further aim to better understand the mechanisms underlying these complications. To achieve these objectives, this application proposes the following specific aims. AIM 1: To determine the feasibility, safety, and efficacy of point-of-care RBC washing using the Continuous AutoTransfusion System (CATS) device in adult cardiac surgery patients receiving allogeneic LR-RBC transfusion. AIM 2: To demonstrate the extent to which point-of-care washing of allogeneic LR-RBCs impacts the recipient response to RBC transfusion when compared to standard-issue allogeneic LR-RBCs. AIM 3: To evaluate the impact of point-of-care washing of allogeneic LR-RBCs on recipient's clinical outcomes. To accomplish these aims, we proposed a multicenter phase I/II randomized clinical trial. Adult cardiac surgery patients receiving allogeneic LR-RBC transfusion will be randomized to receive either point-of-care, washed RBCs using the CATS device or standard-issue RBCs on the day of surgery. A validated risk prediction model will be used to facilitate targeted enrollment into this trial. This proposal addresses multiple highlighted topics in this funding opportunity announcement, including but not limited to: 1) non-infectious complications of blood transfusion including TRALI; 2) immunomodulatory, inflammatory and vasoregulatory properties of transfused blood components; and 3) evaluation of the impact of introducing a new blood product preparation or transfusion strategies on transfusion-associated adverse events and recipients' clinical outcomes.