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：
9066789
负责人：
Daryl J Kor
金额：
$ 62.47万
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/9066789
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 Health Hemoglobin IL8 gene Impact evaluation Inflammatory Infusion procedures Intercellular adhesion molecule 1 Interleukin-6 Intervention Knowledge Left Leukocytes Life Lipids Lung Measures Mechanical ventilation 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 Factors Role Safety Small Inducible Cytokine A3 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 predictive modeling pressure prevent protocol violation 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（由申请人提供）：输血相关的呼吸并发症与输血相关的急性肺损伤（TRALI）和输血相关的循环超负荷（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红细胞（RBC）输血后这些并发症。尽管这些并发症基础的机制仍未完全定义，但据信驻留在RBC存储解决方案中的可溶性生物反应修饰剂（BRMS）起着重要作用。在输血前对同种异体RBC的护理点洗涤可能会消除这些BRM，从而减轻它们对术后呼吸并发症的影响。我们的远程目标是制定可以防止Trali和Taco的有效策略。该提案的目的是使用FDA批准的自发灌注系统来评估护理点洗涤对同种异体白细胞减少（LR）RBC的可行性，安全性，功效和临床影响。我们将专门评估这种干预措施对接受高危心脏手术患者的输血相关呼吸并发症中间标记的影响。我们进一步旨在更好地了解这些并发症的基础机制。为了实现这些目标，本应用程序提出了以下特定目标。目标1：确定护理点的可行性，安全性和功效使用连续自动输血系统（CATS）装置在接受同种异体LR-RBC输血的成人心脏手术患者中洗涤RBC。 AIM 2：与标准发行的同种异体同种异体LR-RBC相比，要证明同种异体LR-RBC的护理点洗涤点在多大程度上影响对RBC输血的受体反应。目标3：评估同种异体LR-RBC的护理点洗涤对受体临床结果的影响。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输血的成年心脏手术患者将随机分配，以在手术当天使用CATS设备或标准 - 发行的RBC接收护理点，洗涤的RBC。经过验证的风险预测模型将用于促进该试验的有针对性入学。该提案介绍了此资助机会公告中的多个突出的主题，包括但不限于：1）包括Trali在内的血液输血的非感染并发症； 2）输血的血液成分的免疫调节，炎症和血管调节特性； 3）评估引入新的血液产品制备或输血策略对输血相关的不良事件和接受者的临床结果的影响。