Sensitivity of Damage Markers for Mechanical Trauma to Erythrocytes in Mechanical Circulatory Support Devices: A Multispecies Study.

Mechanical circulatory support (MCS) advancement relies on fully understanding remaining hemocompatibility issues, including identifying and monitoring a variety of damage markers, as hemolysis alone is insufficient to understand the full scope of total blood damage. It is also important to understand how these alternative markers vary between species, as animal surrogates are often used in device development. This work focuses on evaluating erythrocyte-derived extracellular vesicles (ErEVs) released during MCS perfusion as an alternative marker for monitoring erythrocyte damage. Porcine, bovine, and human washed red blood cells (RBCs) were perfused through a blood circulatory loop using the CentriMag pump. Both hemolysis and ErEV production were monitored over time to compare the sensitivity of both to mechanically induced trauma and to observe species-dependent differences. All species produced significant increases in ErEV concentrations, while only human and bovine erythrocytes produced significant increases in free hemoglobin. There were no differences in the normalized index of hemolysis between species, but bovine RBCs produced significantly more ErEVs than human or porcine, which were similar. Regarding damage marker sensitivity, ErEV generation appears to be a promising complementary marker to hemolysis and potentially more sensitive for porcine and bovine models, while more testing is needed for human.