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

TL;DR

This study uses computational modeling to explore how sickle and normal red blood cells distribute and affect vessel wall shear stress at bifurcations, revealing effects relevant to blood disorders like sickle cell disease.

Contribution

It provides a detailed computational analysis of RBC segregation and margination in bifurcated vessels, highlighting their impact on hemodynamics in sickle cell disease.

Findings

Sickle cells marginate near vessel walls, favoring low-flow branches.

Normal RBCs follow the Zweifach-Fung effect, entering high-flow branches.

Sickle cell accumulation increases high shear stress events, potentially damaging vessels.

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 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.