Flow-induced segregation and dynamics of red blood cells in sickle cell disease

TL;DR

This study uses boundary integral simulations to analyze how sickle cell and healthy red blood cells behave under flow, revealing that sickle cells tend to marginate and cause increased shear stress near vessel walls, which may contribute to endothelial dysfunction.

Contribution

The paper introduces a detailed simulation model comparing sickle and healthy RBCs, highlighting the margination and shear stress effects unique to sickle cells in flow.

Findings

Sickle cells marginate and aggregate near vessel walls.

Sickle cells induce large peaks in wall shear stress.

Healthy RBCs tend to stay centered in the flow.

Abstract

Blood flow in sickle cell disease (SCD) can substantially differ from normal blood flow due to significant alterations in the physical properties of the red blood cells (RBCs). Chronic complications, such as inflammation of the endothelial cells lining blood vessel walls, are associated with SCD, for reasons that are unclear. Here, detailed boundary integral simulations are performed to investigate an idealized model flow flow in SCD, a binary suspension of flexible biconcave discoidal fluid-filled capsules and stiff curved prolate capsules that represent healthy and sickle RBCs, respectively, subjected to pressure-driven flow in a planar slit. The key observation is that, unlike healthy RBCs that concentrate around the center of the channel and form an RBC-depleted layer (i.e. cell-free layer) next to the walls, sickle cells are largely drained from the bulk of the suspension and aggregate inside the cell-free layer, displaying strong margination. These cells are found to undergo a rigid-body-like rolling orbit near the walls. Furthermore, the additional shear stress on the walls induced by the presence of marginated cells is computed. Compared to the small fluctuations in wall shear stress for a suspension of healthy RBCs, large local peaks in wall shear stress are observed for the binary suspensions, due to the proximity of the marginated stiff cells to the walls. As endothelial cells are known to mechanotransduce physical forces such as aberrations in shear stress and convert them to physiological processes such as activation of inflammatory signals, these results may aid in understanding mechanisms for endothelial dysfunction associated with SCD.