Cell Distributions and Segregation During Blood Flow within Curved and Bifurcated Vascular Geometries in Blood Disorders

The spatial distribution of blood cellular components is nontrivial. Red blood cells (RBCs) migrate toward vessel center leaving an RBC-depleted cell-free layer (CFL) near walls, while white blood cells and platelets reside in CFL, a flow-induced segregation termed margination. Margination is significant in blood disorders like sickle cell disease (SCD). A complication of SCD is that endothelial cells are dysfunctional and pro-inflammatory in circulation. One might hypothesize diseased cells strongly marginate, residing primarily in CFL, and generating physical interactions that damage endothelium.

We characterize cell distributions for mixtures of normal and aberrant RBC in various vascular geometries using an immersed boundary method. We test the hypothesis with a range of blood disorders, such as SCD, iron deficiency anemia, COVID-19, and spherocytosis. Smaller and stiffer aberrant RBCs strongly marginate due to contrasts in physical properties relative to normal cells. Marginated aberrant cells near walls causing large stresses fluctuation, potentially leading to increased vascular inflammation. In curved vessels, distribution of marginated cells is very heterogeneous, indicating importance of geometry. In addition, we examine modified Zweifach-Fung (Z-F) effect at vessel bifurcations in blood disorders. Cell segregation results in a thinner CFL, reducing Z-F effect and leads to higher-than-normal hematocrits in low-flow branches, an observation of clinical importance for SCD.