Mechanical Blood Trauma in Assisted Circulation: Sublethal RBC Damage Preceding Hemolysis

Abstract

After many decades of improvements in mechanical circulatory assist devices (CADs), blood damage remains a serious problem during support contributing to variety of adverse events, and consequently affecting patient survival and quality of life. The mechanisms of cumulative cell damage in continuous-flow blood pumps are still not fully understood despite numerous in vitro, in vivo, and in silico studies of blood trauma. Previous investigations have almost exclusively focused on lethal blood damage, namely hemolysis, which is typically negligible during normal operation of current generation CADs. The measurement of plasma free hemoglobin (plfHb) concentration to characterize hemolysis is straightforward, however sublethal trauma is more difficult to detect and quantify since no simple direct test exists. Similarly, while multiple studies have focused on thrombosis within blood pumps and accessories, sublethal blood trauma and its sequelae have yet to be adequately documented or characterized. This review summarizes the current understanding of sublethal trauma to red blood cells (RBCs) produced by exposure of blood to flow parameters and conditions similar to those within CADs. It also suggests potential strategies to reduce and/or prevent RBC sublethal damage in a clinically-relevant context, and encourages new research into this relatively uncharted territory.

Evaluation of energy dissipation rate as a predictor of mechanical blood damage

“…For comparison, the von-Mises-like scalar stress 19,34 is Comparing Equations (16) and (17) reveals that the energy dissipation rate-based scalar stress lacks the normal stress cross-product terms, but weighs the squared normal stress components more heavily than does the von-Mises-like scalar stress. The result is that for 2-D laminar extensional flow, in which σ xx = -σ yy are the only nonzero stress components, e = s .…”

“…Blood flow is mostly laminar in normal physiological conditions, but may become turbulent in larger arteries such as the ascending aorta . Turbulence is arguably more common in mechanical blood‐contacting devices . Therefore, the ideal hemolysis model would seamlessly address laminar and turbulent flow even if both occur in a single device.…”

“…13 Turbulence is arguably more common in mechanical blood-contacting devices. [14][15][16][17] Therefore, the ideal hemolysis model would seamlessly address laminar and turbulent flow even if both occur in a single device.…”

Apheresis red blood cells associated with repeated hemolysis during blood priming of the Cellex Photopheresis System

“…We hypothesize that A‐RBC may exhibit “sublethal” RBC damage following prior exposure to centrifugal shear and negative pressures during collection . Sublethal RBC damage is a recognized phenomenon in extracorporeal circuits and is associated with a decrease in red cell deformability and increased susceptibility to hemolysis, even after exposure to relatively modest shear forces . Sublethal RBC damage, with a 3‐fold increase in mechanical fragility, is also observed after washing RBC with the COBE 2991 cell processor .…”

“…5 damage is a recognized phenomenon in extracorporeal circuits and is associated with a decrease in red cell deformability and increased susceptibility to hemolysis, even after exposure to relatively modest shear forces. 5,6 Sublethal RBC damage, with a 3-fold increase in mechanical fragility, is also observed after washing RBC with the COBE 2991 cell processor. 7 Likewise, Fenwal Alyx A-RBC are reported to have higher free hemoglobin, lower ATP content, and increased membrane rigidity at the time of collection when compared with WB-RBC.…”