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

描述（由申请人提供）：输血相关呼吸系统并发症、输血相关急性肺损伤（TRALI）和输血相关循环负荷（TACO）是输血相关死亡的主要原因。目前，还没有有效的策略来预防红细胞（RBC）输血后这些并发症。尽管这些并发症的机制仍不完全明确，但存在于红细胞储存溶液中的可溶性生物反应调节剂（BRMs）被认为起着重要作用。在输血前的护理点清洗异体红细胞可以清除这些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，以防止TRALI和TACO。本提案的目的是评估使用fda批准的自身输血系统对同种异体白细胞减少（LR）红细胞进行即时清洗的可行性、安全性、有效性和临床影响。我们将特别评估这种干预对高危心脏手术患者输血相关呼吸并发症中间标志物的影响。我们的进一步目标是更好地了解这些并发症的机制。为了实现这些目标，此应用程序提出了以下具体目标。目的1：确定即时护理的可行性、安全性和有效性

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.