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

描述(由申请人提供)：Blaze医疗设备(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)单位的预期疗效。由于供体间的差异、制造方法的差异和红细胞储存时间的延长，输注红细胞的不良反应和不可预测的疗效是需要进行这种测试的前提。大量数据表明，这些差异可能导致对单个红细胞单位质量的模棱两可，仅凭时间是不能充分反映的。在美国，每年输注1500万单位的pRBC，仅次优疗效本身的成本估计就约为170亿美元。红细胞机械脆性(Mf)反映了储存过程中的一系列生化和生物力学变化，并跟踪了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曾被建议作为一种潜在的预测输血结果的体外指标。然而，这一指标的临床相关性仍有待证实。第一阶段研究的假设是，RBC Mf可用作预测RBC输血后存活的综合参数，并且这至少部分与时间无关。在该项目的第一阶段中，BLAZE的具体目标1是确定红细胞机械脆性的可靠性，作为通过增加的患者红细胞压积和总血红蛋白(主要结果)衡量输血后表现的指标；具体目标2是：建立红细胞机械脆性作为通过体内血浆Hb、胆红素、结合珠蛋白和乳酸脱氢酶(次要结果)的溶血标志物衡量输血后表现的可靠性。第二阶段的研究将进一步验证RBC体外MF作为预测输血结果的指标，并优化该测试以用于临床。Blaze将为RBC机械脆性测试提供基本设备和消耗品。Blaze产品的创新可以解决长期存在的MF测试难以标准化以获得广泛接受的问题-利用其专利的光学和处理技术，提供快速可靠的测试，只需非常少的样本即可生成数据丰富的多维脆性轮廓。该项目的长期目标是通过量化-并潜在地预测-红细胞活性的变化来提高输血的有效性和安全性。 储藏室。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，通过从当前的先进先出(FIFO)方法切换到SRSL(最短剩余货架寿命)方法。后续应用可能会扩大，以提供选择和/或筛选具有“不可储存”血液的献血者，评估特定单位是否适合特定的临床用途(例如，g-辐射)，或是否适合特定的患者群体(例如，新生儿、创伤、慢性贫血)。

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).