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.

Figure 1

Bright-field illuminated normal and rigidified erythrocytes undergoing shear at (A) 0 and (B) 1000 s⁻¹ for RBC deformability assessment using the Linkam Shearing Stage. Normal RBCs elongate becoming ellipsoidal under shear stress while the rigid cells remain circular.

Figure 2

(A) Blood of a calf implanted with a CAD (high RBC aggregation and high plasma fibrinogen concentration); (B) Blood of a control calf (no RBC aggregation and low fibrinogen concentration); (C) Control RBCs placed in the CAD animal’s plasma (no RBC aggregation at high fibrinogen concentration); and (D) CAD calf RBCs placed in the control calf plasma (high RBC aggregation despite low fibrinogen concentration) (43). The aggregation present in frames (A) and, especially, (D) indicate that there are RBC-specific changes directly induced by mechanical stress related to CAD support. Reprinted with permission from IOS Press (43).

Figure 3

Effect of suspension media with matched viscosities on bovine RBC mechanical fragility, highlighting the protective effects of plasma proteins and PEG versus Dextran-40 solution, adapted from Kameneva et al (72).