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）：大火医疗设备（Blaze）致力于提高国家血液供应的安全性和功效。 Blaze正在开发一项测试，以量化每个红细胞（RBC）单元的前瞻性功效。这种测试的需求是基于由于抑制性变异性，制造方法的差异和延长的RBC存储而导致的不良反应和不可预测的RBC疗效。重要的数据表明，这些差异可能会导致关于单独时间无法充分反映单个RBC单元质量的歧义。对于美国，每年1500万单位的PRBC输血，次优疗效的成本本身估计约为170亿美元。 RBC机械脆性（MF）反映了储存过程中的一系列生化和生物力学变化，并跟踪红细胞在体内生存所需的可塑性丧失并有效地输送氧气。已提出MF作为体外度量，潜在地预测输血结果。但是，这种度量指标的临床相关性仍然有待证明。第一阶段研究的假设是，RBC MF可以用作转移后RBC存活的总参数，并且至少在部分时间无关。在这个项目中，Blaze的I期特异性目标1是建立RBC机械脆性的可靠性，作为通过渐进的患者血细胞比容和总血红蛋白（主要结果）测量的转移后灌注性能的度量。具体目的2是：建立RBC机械脆性作为通过血浆HB的体内溶血标记，胆红素，Haptoglobin和LDH（次要结果）测量的转移后性能的度量。第二阶段的研究将进一步验证RBC在体外MF中，作为预测输血结果的指标，并优化了临床使用测试。 Blaze将为RBC机械脆弱性测试提供基础设备和消耗品。 Blaze产品的创新可以解决MF测试的长期问题，难以对广泛的可接受性进行标准化 - 通过提供快速可靠的测试，该测试几乎不需要样品来生成富含数据的多维脆性曲线，并利用其专利的光学和处理技术。该项目的长期目标是通过量化（有可能预测）在RBC生存能力的变化来提高输血的功效和安全性 贮存。作为第一个商业应用程序，Blaze的测试将使医院血库清单更有效地管理 - 例如，通过从当前的FIFO（首先）切换到SRSL（剩余的保质期最短）方法。可以潜在地扩展随访应用，以提供“不可遗传”血液的选择和/或筛查供体，评估给定单位对特定临床使用的适用性（例如G-irradiation）或适合特定患者群体（例如新生儿，创伤，创伤，慢性贫血）。