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

• 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
• 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

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 Medical Devices（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，以量化每个红细胞（RBC）单位的预期功效。由于供体间变异性、制造方法的差异和RBC储存时间延长，输注RBC的不良反应和不可预测的疗效决定了是否需要进行此类检测。重要数据表明，这些差异可能导致单个RBC单位质量的不确定性，仅凭时间无法充分反映。在美国，每年输注1500万单位的pRBC，次优疗效本身的成本估计约为170亿美元。RBC机械脆性（MF）反映了储存期间的一系列生化和生物力学变化，并跟踪红细胞在体内存活和有效输送氧气所需的可塑性损失。MF已被提议作为潜在预测输血结局的体外指标。然而，这种度量的临床相关性仍有待证明。I期研究的假设是，RBC MF可用作预测输血后RBC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I期具体目标1是建立RBC机械脆性的可靠性，作为通过增加患者红细胞压积和总血红蛋白测量的输血后性能指标（主要成果）;具体目标2是：建立RBC机械脆性作为通过血浆Hb，胆红素，结合珠蛋白和LDH（次要结局）。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机械脆性试验提供基础器械和耗材。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-通过利用其专利的光学和处理技术提供快速可靠的测试，只需很少的样品即可生成数据丰富的多维脆性曲线。该项目的长期目标是通过量化-并可能预测-输血过程中RBC活力的变化来提高输血的有效性和安全性。 存储.作为第一个商业应用，Blaze的测试将使医院血库库存的管理更加有效-例如，通过从当前的FIFO（先进先出）切换到SRSL（最短剩余保质期）方法。后续应用可以潜在地扩展到提供对具有“不可储存”血液的供体的选择和/或筛选，评估给定单元对于特定临床用途（例如，辐照）的适用性，或对于特定患者群体（例如，新生儿、创伤、慢性贫血）的适用性。