Determinants of blood viscosity in SCD. In vitro models have demonstrated higher whole blood viscosity in SCD blood samples compared with non-SCD samples. The viscosity of sickle blood increases with deoxygenation, low shear rates, and higher HbS concentration, which cause increased HbS polymerization and sickling. Less deformable and denser red cells, as well as increased cellular adhesivity, also raise the viscosity of sickle blood. Additionally, in vivo, vasculopathy and endothelial dysfunction may contribute to increased blood viscosity and vaso-occlusion in the microcirculation.