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).
Proposed project aims to preliminary validate in-vitro Red Blood Cell membrane Mechanical Fragility (MF) as evaluated through MF profiles - e.g., induced hemolysis vs. applied stress duration/magnitude - as a candidate metric predictive of safety and performance of blood- handling devices. While current assessments of induced blood damage by blood-handling devices rely primarily on hemolysis, they do not account for possible 'sub-hemolytic' RBC damage, which can significantly impact devices' performance and thus outcomes, hence the need for more 'comprehensive' assessment of induced blood damage.
