Validation of packed Red Blood Cell Mechanical Fragility to Indicate Transfusion Outcomes

验证浓缩红细胞机械脆性以指示输血结果

基本信息

批准号：
8830110
负责人：
ROBERTSON D DAVENPORT
金额：
$ 21.26万
依托单位：
BLAZE BIOMEDICAL DEVICES, LLC
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：
2014-12-01 至 2017-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8830110
关键词：
Accounting Adoption Adverse effects Adverse event Age Anemia Area Basic Science Bilirubin Biochemical Biomechanics Blood Blood Banks Blood Transfusion Capital Cell Survival Cell membrane Cells Chronic Clinical Clinical Research Data Devices Diagnostic Dialysis procedure Donor Selection Double Effect Equipment and supply inventories Erythrocyte Transfusion Erythrocytes Evaluation Feedback Funding Goals Haptoglobins Hematocrit procedure Hemoglobin Hemolysis Hospital Administration In Vitro Individual Investments Legal patent Length of Stay Lesion Life Market Research Marketing Measurement Measures Mechanics Medical Device Medicine Membrane Methods Microcirculation Neonatal Optics Outcome Oxygen Pathway interactions Patients Performance Phase Plasma Procedures Process Property Research Safety Sales Sampling Sickle Cell Anemia Stress System Techniques Technology Testing Time Transfusion Trauma Triage Validation Vascular blood supply base clinically relevant cohort commercial application cost follow-up improved in vivo innovation interest irradiation phase 1 study primary outcome product development prospective public health relevance research and development secondary outcome success technological innovation

项目摘要

DESCRIPTION (provided by applicant): Blaze Medical Devices (Blaze) is dedicated to improving the safety and the efficacy of the nation's blood supply. Blaze is developing a test to quantify the prospective efficacy of each Red Blood Cell (RBC) unit. The need for such testing is predicated upon the adverse effects and unpredictable efficacy of transfused RBC due to inter-donor variability, differences in manufacturing methods and prolonged RBC storage. Significant data show that these differences can cause ambiguities about the quality of individual RBC units that time alone cannot adequately reflect. For 15 million units of pRBC transfused annually in the US, the cost of suboptimal efficacy by itself has been estimated at about $17 billion. RBC mechanical fragility (MF) reflects an array of biochemical and biomechanical changes during storage, and tracks the loss of plasticity that red blood cells need to survive in vivo and to deliver oxygen effectively. MF had been proposed as an in-vitro metric potentially predictive of transfusion outcomes. However, the clinical relevance of such a metric still remains to be demonstrated. The hypothesis of the Phase I research is that RBC MF can be used as an aggregate parameter predictive of RBC survival post-transfusion, and that this is at least partially time-independent. In this project Blaze's Phase I Specific Aim 1 is to establish the reliability of RBC mechanical fragility as a metric of post-transfusion performance measured through incremental patient hematocrit and total hemoglobin (primary outcomes); and Specific Aim 2 is: to establish the reliability of RBC mechanical fragility as a metric of post-transfusion performance measured through in vivo hemolysis markers of plasma Hb, bilirubin, haptoglobin and LDH (secondary outcomes). Phase II research will further validate the RBC in vitro MF as a metric to predict transfusion outcomes, and optimize the test for clinical use. Blaze will provide base devices and consumables for RBC mechanical fragility testing. The innovation of Blaze's product can solve the longstanding problem of MF testing being difficult to standardize for wide acceptability - by offering a rapid and reliable test that requires very little sample to generate data- rich multi-dimensional fragility profiles, by utilizing its patented optical and processing techniques. The long-term goal of the project is to improve the efficacy and safety of blood transfusions through quantifying - and potentially predicting - the changes in RBC viability during storage. As a first commercial application, Blaze' test will enable more efficient management of Hospital Blood Bank inventories - for example, by switching from the current FIFO (First-In-First-Out) to a SRSL (Shortest Remaining Shelf Life) approach. Follow-up applications can be potentially expanded to provide for selection and/or screening of donors with "non-storable" blood, assessing a given unit's suitability for a particular clinical use (e.g. g-irradiation), or suitability for particular patient groups (e.g. neonatal, trauma, chronic anemia).

描述（由申请人提供）：Blaze 医疗器械（Blaze）致力于提高国家血液供应的安全性和有效性。 Blaze 正在开发一种测试来量化每个红细胞 (RBC) 单位的预期功效。进行此类测试的必要性在于，由于捐赠者之间的差异、制造方法的差异和红细胞储存时间延长，输注红细胞会产生不良影响和不可预测的功效。重要数据表明，这些差异可能会导致单个红细胞单位质量的模糊性，而仅凭时间无法充分反映这一点。美国每年输注 1500 万单位的 pRBC，其疗效不佳本身的成本估计约为 170 亿美元。红细胞机械脆性 (MF) 反映了储存过程中一系列生化和生物力学变化，并追踪红细胞在体内生存和有效输送氧气所需的可塑性的丧失。 MF 被提议作为一种可能预测输血结果的体外指标。然而，这种指标的临床相关性仍有待证明。 I 期研究的假设是，红细胞 MF 可用作预测输血后红细胞存活率的综合参数，并且这至少部分与时间无关。在该项目中，Blaze 的第一阶段具体目标 1 是确定红细胞机械脆性的可靠性，作为通过增量患者血细胞比容和总血红蛋白（主要结果）测量的输血后性能指标；具体目标 2 是：确定红细胞机械脆性的可靠性，作为通过血浆 Hb、胆红素、触珠蛋白和 LDH 等体内溶血标志物测量的输血后性能指标（次要结果）。 II 期研究将进一步验证 RBC 体外 MF 作为预测输血结果的指标，并优化临床使用的测试。 Blaze 将为 RBC 机械脆性测试提供基础设备和耗材。 Blaze 产品的创新可以解决 MF 测试难以标准化以获得广泛接受的长期问题 - 通过提供快速可靠的测试，只需很少的样本即可生成数据丰富的多维易碎性曲线，利用其专利光学和加工技术。该项目的长期目标是通过量化并可能预测输血期间红细胞活力的变化来提高输血的有效性和安全性。贮存。作为第一个商业应用，Blaze 的测试将能够更有效地管理医院血库库存，例如，从当前的 FIFO（先进先出）方法切换到 SRSL（最短剩余保质期）方法。后续应用可以潜在地扩展，以提供“不可储存”血液供体的选择和/或筛选，评估给定单位对特定临床用途（例如 g 辐射）的适用性，或对特定患者群体的适用性（例如新生儿、外伤、慢性贫血）。