Suspension physics govern the multiscale dynamics of blood flow in sickle cell disease

From diabetes to malaria, altered blood flow contributes to poor clinical outcomes. Heterogeneity in red blood cell (RBC) properties within and across individuals has hindered our ability to establish the multiscale mechanisms driving pathological flow dynamics in such diseases. To address this, we develop microfluidic platforms to measure RBC properties and flow dynamics in the same blood samples from patients with sickle cell disease (SCD). We find that effective blood viscosity across individuals is explained by the proportion of stiff RBCs, exhibiting qualitative similarities to rigid-particle suspensions, despite considerable mechanical heterogeneity. By combining simulations with spatially resolved measurements of cell dynamics, we show how features of emergent rheology are governed by spatiotemporal cell organization, via margination at intermediate oxygen tensions, and localized jamming caused by spatial hematocrit variations under hypoxia. Our work defines the suspension physics underlying pathological blood flow in SCD and, more broadly, emergent rheology in heterogeneous particle suspensions.