Red blood cell partitioning and segregation through vascular bifurcations in a model of sickle cell disease

Abstract

The impact of cell segregation and margination in blood disorders on microcirculatory hemodynamics within bifurcated vessels are physiologically significant, yet poorly understood. This study presents a comprehensive computational investigation of red blood cell (RBC) suspension dynamics, with a focus on a model of sickle cell disease (SCD) as an example of a disorder associated with subpopulations of aberrant RBCs. The findings reveal how cell margination influences cellular partitioning and distributions as well as vessel wall shear stress (WSS) at vascular bifurcations. Normal RBCs, which migrate toward the channel center, exhibit the Zweifach-Fung effect, preferentially entering high-flow-rate branches. In contrast, sickle cells, which marginate near the vessel wall, demonstrate an \textit{anti}-Zweifach-Fung effect, favoring lower-flow-rate branches due to their position within the cell-free layer (CFL). The upstream segregation of cells remains downstream through the bifurcation, where sickle cells accumulate along the outer branch walls. This accumulation of sickle cells increases the frequency of high WSS events via direct physical interactions, particularly on the outer side of high-velocity branches, potentially contributing to the vascular damage and endothelial disruption observed in many disorders that affect RBCs. In geometrically asymmetric bifurcations, cells preferentially enter branches with larger radii, underscoring the influence of geometric complexity on microcirculatory blood flow. These findings provide insights into microvascular hemodynamics in SCD and other blood disorders.