The hypothesis for this study was that RBC mechanical fragility (MF) could be an aggregate in vitro property predictive of transfused RBC performance in vivo. Various MF values were obtained via MF profiling, based on several variations of testing parameters, using both a "legacy" approach (with a commercial, cam-based vertical bead mill and a spectrophotometer) and a more proprietary approach (with a custom-developed, electromagnetic horizontal bead mill combined with proprietary optics and analysis). A total of 52 transfusion events in 32 different patients recruited from the University of Michigan were included in this study. Results were assessed using mixed effects and linear regression models. RBC MF was shown to predict about 15% of transfusion-associated changes in patient hemoglobin concentration, but not of secondary hemolysis-associated metrics (serum hemoglobin, HAP, and LDH). This result was affected by several factors that were not fully accounted for, including variability in post-transfusion blood collection time and variability in each blood unit volumes. Inclusion of the number of units transfused showed the potential to improve predictive capability, thus highlighting the potential importance of underlying patient condition necessitating the second unit transfusion. Certain ways of applying the bead-induced mechanical stress showed MF results more suitable for predicting transfusion outcomes than others indicating potential significance of flow stress type for assessing storage-induced RBC membrane damage. That highlights an opportunity for improvement of the potential for use of MF metrics, through identification of optimal stress application parameters (possibly by further varying parameters used here, as well as others) for assessing contribution of storage-lesion-associated RBC damage on transfused RBC performance.

Authors Tarasev, Chakraborty, Alfano, and Muchnik were employed during this work by Blaze Medical Devices, a company that developed the RBC MF testing technology used in this work. Authors Tarasev, Chakraborty, and Alfano own equity in Blaze. Author Alfano contributed to the work solely in his capacity with Blaze. Authors Tarasev and Gao are presently employed with Functional Fluidics, a company that now holds exclusive rights in the technology developed by Blaze, and which has performed further analysis of the study data after the initial work was complete.

This work was funded by a Phase 1 SBIR grant from NIH/NHLBI (#1R43HL121865-01A1)to Blaze Medical Devices.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

University of Michigan Institutional Review Board gave ethical approval for this work.

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All data produced in the present study are available upon reasonable request to the authors