The role of blood rheology in sickle cell disease

Abstract

Studies performed in the last decades have highlighted the need to better understand the contribution of the endothelium, vascular function, oxidative stress, inflammation, coagulation, hemolysis and vascular adhesion mechanisms to the pathophysiology of acute vaso-occlusive like events and chronic organ damages in sickle cell disease (SCD). Although SCD is a hemorheological disease, a few works focused on the contribution of blood viscosity, plasma viscosity, red blood cell deformability and aggregation in the pathophysiology of SCD. After a brief description of basic hemorheology, the present review focuses on the role of the hemorheological abnormalities in the causation of several SCD complications, mainly in sickle cell anemia and hemoglobin (Hb) SC disease. Several genetic and cellular modulators of blood rheology in SCD are discussed, as well as unresolved questions and perspectives.

Keywords: Blood viscosity; Red blood cell aggregation; Red blood cell deformability; Sickle cell disease; Vaso-occlusive crises.

Fig. 1

Effects of shear rate and red blood cell rheological properties on blood viscosity. This figure shows the shear-thinning properties of blood, with blood viscosity decreasing when shear rate increases. At low shear rates, blood viscosity mainly depends on red blood cell aggregation. As the shear rate increases, red blood cell aggregates progressively dissociate. At high shear rate, the ability of red blood cell to deform under shear affects blood viscosity. The figure also gives information about the shear rate values that can be found in the vascular system [–111]. In a given vessel, shear rate can be estimated by 8 * mean centerline blood velocity / diameter of the vessel. Photography (courtesy of Dr. Max R Hardeman): on the left = red blood cell aggregates; on the right: red blood cell in the process of deforming to pass through a micropore of 5 μm.

Fig. 2

Effects of time exposure at a fixed shear rate on blood viscosity. This figure shows the decrease over time (2 min) of blood viscosity when the fluid is sheared at 10 s⁻¹, which reflects the thixotropic property of blood. The progressive rupture of red blood cell aggregates over time makes the blood less viscous.

Fig. 3

Blood viscosity vs shear rate curves in healthy individuals, SC and SCA patients at adjusted hematocrit (40%). The second graphic (at the bottom) shows the same data than the first one (at the top) but shear rate values are log transformed to better see the difference at low shear rates. The two sickle cell groups exhibit higher blood viscosity at 40% hematocrit than the healthy population because of the presence of robust red blood cell aggregates and rigid red blood cells.