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

描述（由申请人提供）：输血相关呼吸并发症、输血相关急性肺损伤（TRALI）和输血相关循环超负荷（TACO）是输血相关死亡的主要原因。目前，没有有效的策略来预防这些并发症后的红细胞（RBC）输注。虽然这些并发症的机制仍然不完全确定，可溶性生物反应调节剂（BRM）驻留在红细胞储存溶液中被认为发挥了重要作用。在输血前对同种异体RBC进行护理点清洗可以去除这些BRM，从而减轻其对术后呼吸并发症的影响。我们的长期目标是制定有效的战略，可以防止TRALI和TACO。本提案的目的是评价使用FDA批准的自体输血系统对同种异体白细胞减少（LR）RBC进行床旁清洗的可行性、安全性、有效性和临床影响。我们将专门评估这种干预对接受高风险心脏手术的患者中输血相关呼吸并发症的中间标志物的影响。我们进一步的目标是更好地了解这些并发症的机制。为了实现这些目的，本申请提出了以下具体目标。目的1：确定床旁技术的可行性、安全性和有效性 在接受同种异体LR-RBC输注的成人心脏手术患者中使用连续自动输血系统（CATS）器械进行RBC清洗。目标2：证明与标准同种异体LR-RBC相比，同种异体LR-RBC的床旁清洗对受体RBC输注反应的影响程度。目的3：评估同种异体LR-RBC的床旁清洗对受体临床结局的影响。为了实现这些目标，我们提出了一个多中心I/II期随机临床试验。接受同种异体LR-RBC输注的成人心脏手术患者将在手术当天随机接受使用CATS器械的床旁清洗RBC或标准问题RBC。将使用经验证的风险预测模型促进本试验的目标入组。该提案涉及本资助机会公告中的多个重点主题，包括但不限于：1）输血的非感染性并发症，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）评估引入新的血液制品制备或输血策略对输血的影响-相关的不良事件和接受者的临床结果。

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.