Validation of Red Blood Cell Mechanical Fragility as a Metric for Assessing Blood Damage Caused by Implantable Ventricular Assist DEvices

验证红细胞机械脆性作为评估植入性心室辅助装置引起的血液损伤的指标

• 批准号: 8902464
• 负责人: Francis D Pagani
• 金额: $ 15万
• 依托单位: BLAZE BIOMEDICAL DEVICES, LLC
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-15 至 2018-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8902464
• 关键词: Validation; Red; Blood; Cell; Mechanical

 DESCRIPTION (provided by applicant): Blaze Medical Devices (Blaze) is developing a rapid integrated test for RBC mechanical fragility (MF) as a potential indicator of safety and performance of blood-handling devices. The safety and performance of blood-handling devices such as VADs are evaluated by hemocompatibility testing to assess the damage they inflict upon red blood cells (RBC). The chief indicator of this damage is the amount of hemolysis induced by a device as it interacts with the blood. However, hemolysis alone fails to ascertain "sub-hemolytic" damage that is not cell-lethal, but is nevertheless important to know as it can reflect susceptibility to future hemolysis (in vivo) and its associated known problematic consequences. The mechanical fragility (MF) of the RBC has been recognized in the literature as a more sensitive metric of cell damage than hemolysis alone, but the lack of a standardized/well-accepted test for it has also been noted in the literature (and even cited by medical insurers). Blaze is providing the first rapid and convenient test for RBC MF, via a bench-top device using single-use consumable cartridges for each sample. The technological innovation of Blaze's product includes patented means to quantify hemolysis in a sample without the need to centrifuge or otherwise separate, as well as a patented approach to gathering fragility profiles via automated varying of multiple stress parameters. The long-term goal is to validate MF's use in assessing safety and performance of blood-handling devices. The hypothesis for the Phase I research is that RBC mechanical fragility will reflect differences in performance between the two mechanical assist devices (centrifugal LVAD HeartMate II and axial HeartWare HVAD), and that further it can be used to monitor the post-op performance of blood handling devices (based on the correlation between RBC MF and post-operative VAD implant outcomes). This project aims to preliminarily validate this hypothesis on a cohort of 20 patients scheduled for implantation (10 of each). Phase 1 Specific Aims: 1) Validate RBC mechanical fragility (MF) as a potential metric of blood damage caused by implantable blood-contacting devices; 2) Establish the differences in blood damage from an axial flow LVAD with bearing design (Thoratec HeartMate II) and a centrifugal flow LVAD with bearing-less design (HeartWare HVAD) by RBC MF; 3) Establish the variability in blood damage caused by implantable blood-contacting devices across different patients. Phase II research will include larger-scale follow-up work both quantitatively (e.g. sample sizes sufficient to evaluate MF changes as a predictor for thrombosis) and qualitatively (e.g. more devices tested and/or stratified patient groupings for more thorough analyses).

 描述（由申请人提供）：Blaze Medical Devices（Blaze）正在开发一种RBC机械脆性（MF）快速综合试验，作为血液处理器械安全性和性能的潜在指标。血液处理器械（如VAD）的安全性和性能通过血液相容性试验进行评价，以评估它们对红细胞（RBC）造成的损伤。这种损伤的主要指标是器械与血液相互作用时引起的溶血量。然而，单独的溶血不能确定不是细胞致死性的“亚溶血”损伤，但仍然重要的是要知道，因为它可以反映对未来溶血（体内）的易感性及其相关的已知问题后果。RBC的机械脆性（MF）在文献中被认为是比单独溶血更敏感的细胞损伤指标，但文献中也注意到缺乏标准化/公认的测试（甚至被医疗保险公司引用）。Blaze是第一个快速方便的RBC MF测试，通过一个台式设备使用一次性耗材盒为每个样本。Blaze产品的技术创新包括无需离心或以其他方式分离即可量化样品中溶血的专利方法，以及通过自动改变多个应力参数来收集脆性曲线的专利方法。长期目标是验证MF在评估血液处理器械安全性和性能方面的用途。I期研究的假设是，RBC机械脆性将反映两种机械辅助器械（离心式LVAD HeartMate II和轴向HeartWare HVAD）之间的性能差异，并且还可用于监测血液处理器械的术后性能（基于RBC MF与术后VAD植入结局之间的相关性）。本项目旨在对计划植入的20例患者（各10例）队列初步验证该假设。第1阶段具体目标：1）红细胞机械脆性（MF）作为植入式血液接触器械引起的血液损伤的潜在指标; 2）确定具有轴承设计的轴流式LVAD的血液损伤差异（Thoratec HeartMate II）和无轴承设计的离心式LVAD（HeartWare HVAD）; 3）确定不同患者之间植入式血液接触器械引起的血液损伤的变异性。II期研究将包括定量（例如，样本量足以评价MF变化作为血栓形成预测因素）和定性（例如，更多器械试验和/或分层患者分组以进行更全面的分析）的更大规模随访工作。