Susceptibility of density-fractionated erythrocytes to subhaemolytic mechanical shear stress

Abstract

Red blood cell populations respond differently to mechanical stimuli: older (more dense) cells are highly susceptible to sublethal mechanical trauma, while cell age (density) does not appear to alter the magnitude of improved cell deformability following low-shear conditioning.

Mechanical sensitivity of red blood cells improves in individuals with hemochromatosis following venesection therapy

“…20 It is possible that venesection treatment positively affects the subhemolytic threshold of RBCs by increasing RBC turnover and thus also reducing the relative proportion of older and oxidatively damaged RBC, which have reduced mechanical properties. 28 It has been reported that venesection therapy decreased oxidative stress markers and increased the bioavailability of various antioxidants 23 ; these findings support that the improved mechanical properties in the present study subsequent to venesection therapy may be related to an improved redox state of RBCs. Although speculative, it is important to consider that serum ferritin is considered an important inflammatory marker, 34 and thus the decrease in serum ferritin observed in the current study may also suggest a decrease in systemic inflammation of volunteers, potentially contributing to the improved cell mechanics.…”

“…Additionally, while a single venesection may remove longer circulating (ie, older) RBCs, decreases in blood volume concurrently increase circulating levels of erythropoietin (ie, the hormonal stimulus for erythropoiesis), 27 thus triggering increased synthesis of younger RBC with improved mechanical capabilities. 28 Collectively, our data suggest that venesection therapy is effective at improving cellular deformability in HH; however, it may be of clinical value to examine whether these improvements translate to enhanced microcirculatory function in individuals with HH. Given that it has been recently demonstrated that impaired cell mechanics, at least in sickle cell disease, negatively impacts microcirculatory function and tissue oxygenation, 16 this area of investigation appears meaningful.…”

“…Given that venesection therapy has been reported to decrease markers of oxidative stress in individuals with HH, 23 it is possible that decreased oxidative damage of RBC may explain, at least in part, the presently observed improvement in RBC deformability with follow‐up venesection treatments. Additionally, while a single venesection may remove longer circulating (ie, older) RBCs, decreases in blood volume concurrently increase circulating levels of erythropoietin (ie, the hormonal stimulus for erythropoiesis), 27 thus triggering increased synthesis of younger RBC with improved mechanical capabilities 28 . Collectively, our data suggest that venesection therapy is effective at improving cellular deformability in HH; however, it may be of clinical value to examine whether these improvements translate to enhanced microcirculatory function in individuals with HH.…”

Sublethal mechanical shear stress increases the elastic shear modulus of red blood cells but does not change capillary transit velocity

“…This heterogenic response for the shear elastic modulus of single RBCs following exposure to sublethal mechanical stress has not been previously reported, and precise mechanisms dictating (non)response to shear damage remain to be elucidated. Recent work 34 presents a plausible explanation, however, for such disparity in the present individual cell responses: Subpopulations that arise due to physiological “aging” respond differently to mechanical shear, where the most dense RBCs (older cells) accumulate shear rigidification at more than twice the rate of the less dense counterparts (younger cells).…”

Blood damage in ventricular assist devices

“…Recent observations in erythrocyte responses to shear stress suggest that not all blood cells respond equally to The International Journal of Artificial Organs 42 (3) shear history; the working hypothesis of this observation is that older cells may be more susceptible to the effects of shear exposure when compared with younger cells. McNamee et al 7 thus contributed a simple experimental model of erythrocyte response to shear stresses known to impact cellular deformability, with a novel approach to explore whether the least dense (young) or most dense (old) cells respond equivalently. These authors present findings supporting that older cells tend to demonstrate higher levels of impaired cell deformability following sublethal shear exposure, and with substantially shorter exposure durations.…”