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

简介（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，以量化每个红细胞（RBC）单位的预期功效。由于供者之间的差异、制造方法的差异和红细胞储存时间的延长，输血红细胞的副作用和不可预测的疗效是需要这种检测的。重要的数据表明，这些差异可能导致个体红细胞单位质量的模糊，单凭时间无法充分反映。在美国，每年输注1500万单位的pRBC，其效果欠佳的成本估计约为170亿美元。红细胞机械脆弱性（MF）反映了储存过程中的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已被提议作为一种体外指标，可能预测输血结果。然而，这种指标的临床相关性仍有待证实。I期研究的假设是，RBC MF可以用作预测输血后红细胞存活的综合参数，并且至少部分与时间无关。在该项目中，Blaze的I期具体目标1是通过增加患者红细胞压积和总血红蛋白（主要结果），建立RBC机械脆弱性作为输血后表现指标的可靠性；具体目标2是：通过血浆Hb、胆红素、触珠蛋白和LDH的体内溶血标志物（次要结局），建立红细胞机械脆弱性作为输血后表现指标的可靠性。II期研究将进一步验证红细胞体外MF作为预测输血结果的指标，并优化临床使用的测试。Blaze将提供RBC机械易碎性测试的基础设备和耗材。Blaze产品的创新可以解决长期存在的MF测试难以标准化的问题，通过提供快速可靠的测试，只需很少的样本就可以生成数据丰富的多维脆弱性剖面，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和潜在地预测输血过程中红细胞活力的变化来提高输血的有效性和安全性

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).