Journal of Clinical Trials
Open Access

Abstract

Use of Packed Red Blood Cell Mechanical Fragility to Indicate Transfusion Outcomes

Tarasev M*, Chakraborty S, Alfano K, Muchnik M, Gao X and Davenport R

Objective: The hypothesis for this study was that packed Red Blood Cell (pRBC) Mechanical Fragility (MF) could be an aggregate in vitro property predictive of transfused pRBC 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).

Methods: A total of 52 transfusion events in 32 different patients recruited from the University of Michigan were included in this study, with the primary outcome being the change in patient hemoglobin per pRBC unit transfused (adjusted to the patient blood and transfused pRBC volumes). Results were assessed using mixed effects and linear regression models.

Results: RBC MF, as determined at some parameter variations, was shown to predict about 15% of transfusion associated changes in patient hemoglobin concentration. RBC MF had no significance as a predictor of transfusion associated changes in LDH and HAP; however, under some testing configurations, it was a strong predictor of changes in serum Hb (p<0.05; R²=0.42). These results were affected by several factors that were not fully accounted for, including variability in post-transfusion time until sample collection from patients, and variability in transfused volume of pRBC across blood units. Inclusion of the number of units transfused per transfusion event showed the potential to raise the test’s predictive capability up to about 30%, thus highlighting the potential importance of underlying patient condition necessitating the second-unit transfusion.

Conclusion: RBC MF (reflecting a lack or limit of cell stability under external mechanical stress) can be predictive of packed red cell survival in vivo after transfusion. Certain ways of applying bead-induced mechanical stress show MF results more suitable for predicting transfusion outcomes than others, indicating a potential significance of flow stress type for assessing storage-induced RBC membrane damage. That highlights an opportunity for improvement of the potential for using MF metrics, through identification of optimal stress application parameters (possibly by further varying parameters used here, as well as others) for assessing the contribution of storage-lesion-associated RBC damage on transfused RBC performance.

Published Date: 2022-08-03; Received Date: 2022-07-03