Microcirculatory blood flow with aberrant levels of red blood cell aggregation

Abstract: Recent clinical results indicate that aberrant erythrocyte aggregation in hematological disorders is accompanied by endothelial damage and glycocalyx disruption, but the underlying biophysical mechanisms remain unclear. This study uses direct computational modeling to explore how red blood cell (RBC) aggregation impacts shear stress in small blood vessels, highlighting the increased risk of vascular damage. RBC aggregation creates a heterogeneous distribution, leading to variations in the cell-free layer thickness and fluctuating wall shear stress, especially near vessel walls. This effect aligns with experimental findings on endothelial disruption linked to RBC clustering near the wall, potentially reducing the protective glycocalyx layer. The power spectral density analysis of wall shear stress fluctuations reveals that, with RBC aggregation, there is a distinct peak near frequency f = 0.04, indicating increased fluctuations due to aggregated RBC clusters traveling close to the vessel wall. The presence of aberrant cells in blood disorders, modeled here by sickle cells, further amplifies these effects, as aggregation-enhanced margination drives sickle cells closer to vessel walls, exacerbating shear stress fluctuations and increasing the likelihood of vascular injury and inflammation. Simulations show that curved vascular geometry, with curvature accentuating RBC clustering near vessel walls, intensifies aggregation-induced wall shear stress fluctuations and increases the risk of vascular damage, particularly in sickle cell disease where sickle cells marginate closer to the wall.