Defining the contribution of red blood cell mechanical properties to altered rheology in sickle cell disease

In sickle cell disease (SCD), polymerization of hemoglobin under deoxygenated conditions causes red blood cells (RBCs) to stiffen, resulting in aberrant blood flow. At the continuum level, deoxygenated blood in SCD exhibits increased shear-thinning and wall friction but it is not understood how the distribution of RBC properties contributes to whole-blood rheology. To this end, we developed an experimental-computational platform to probe the effect of oxygen-dependent RBC stiffness and volume fraction on blood properties. Simulations of mixed suspensions of healthy and stiff RBCs suggested that margination of stiff RBCs contributes to decreased RBC speeds near the wall and thus an increase in whole-blood wall friction. These predictions were tested experimentally using a method in which sickle RBCs were stained fluorescently and tracked in a mixture of healthy blood under deoxygenated conditions. At high stiff cell fractions, theory and experiments showed a decrease in mean RBC speed and therefore an increase in total flow resistance. Furthermore, we tested theoretically and experimentally how frictional forces between stiffened cells affect the observed blood rheology. Results from this work will advance our general understanding of particle suspension flows and help identify mechanisms that contribute to pathological blood flow in SCD.