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

护理点红细胞清洗以预防输血相关的肺部并发症

基本信息

批准号：
8611159
负责人：
Daryl J Kor
金额：
$ 65.55万
依托单位：
MAYO CLINIC ROCHESTER
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-09-15 至 2019-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8611159
关键词：
Acute Acute Lung Injury Address Adoption Adult Adverse event Allogenic Autologous Blood Transfusion Biological Markers Biological Response Modifiers Blood Blood Banks Blood Platelets Blood Transfusion CD40 Ligand Cardiac Surgery procedures Cardiopulmonary Bypass Cells Cellular Structures Cessation of life Childhood Clinical Clinical Trials Data Day Surgery Devices Enrollment Environment Equipoise Erythrocyte Transfusion Erythrocytes FDA approved Functional disorder Funding Opportunities Goals Hemoglobin IL8 gene Impact evaluation Inflammatory Infusion procedures Intercellular adhesion molecule 1 Interleukin-6 Intervention Knowledge Left Leukocytes Life Lipids Lung Measures Mechanical ventilation Modeling Morbidity - disease rate Operative Surgical Procedures Organ Outcome Oxygen Patients Perioperative Peripheral Resistance Phase Physiological Plasma Plasminogen Activator Inhibitor 1 Play Population Populations at Risk Postoperative Period Preparation Prevention strategy Preventive Intervention Property Pulmonary Capillary Wedge Pressure Pulmonary Surfactant-Associated Protein D RANTES Randomized Randomized Clinical Trials Reaction Research Research Infrastructure Risk Risk Factors Role Safety Small Inducible Cytokine A3 Solutions Stimulus Supplementation System Testing Time Transfusion United States Ursidae Family VWF gene Ventricular blood product clinical efficacy cohort experience high risk improved inflammatory marker injury prevention innovation lung injury multidisciplinary patient oriented point of care pressure prevent protocol violation public health relevance respiratory response success

项目摘要

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.

描述（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）和输血相关循环超负荷（TACO）是输血相关死亡的主要原因。目前，尚无有效的策略来预防红细胞（RBC）输注后的这些并发症。尽管这些并发症的机制尚未完全确定，但红细胞储存溶液中的可溶性生物反应调节剂 (BRM) 被认为发挥着重要作用。输血前对同种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系统并发症的影响。我们的长期目标是制定有效的策略来预防 TRALI 和 TACO。该提案的目的是评估使用 FDA 批准的自体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。我们将专门评估这种干预措施对接受高危心脏手术的患者输血相关呼吸系统并发症中间标志物的影响。我们进一步的目标是更好地了解这些并发症的机制。为了实现这些目标，本申请提出以下具体目标。目标 1：确定现场护理的可行性、安全性和有效性使用连续自动输血系统 (CATS) 装置对接受同种异体 LR-RBC 输注的成人心脏手术患者进行红细胞清洗。目标 2：与标准同种异体 LR-RBC 相比，证明同种异体 LR-RBC 的护理点清洗对受体对红细胞输注的反应的影响程度。目标 3：评估同种异体 LR-RBC 的即时清洗对受者临床结果的影响。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。接受同种异体 LR-RBC 输注的成人心脏手术患者将被随机分配接受使用 CATS 装置冲洗的护理点红细胞或手术当天接受标准红细胞。将使用经过验证的风险预测模型来促进有针对性地参加该试验。该提案涉及本次融资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）输注血液成分的免疫调节、炎症和血管调节特性； 3) 评估引入新的血液制品制剂或输血策略对输血相关不良事件和接受者临床结果的影响。