Patient-specific blood rheology in sickle-cell anaemia

Abstract

Sickle-cell anaemia (SCA) is an inherited blood disorder exhibiting heterogeneous cell morphology and abnormal rheology, especially under hypoxic conditions. By using a multiscale red blood cell (RBC) model with parameters derived from patient-specific data, we present a mesoscopic computational study of the haemodynamic and rheological characteristics of blood from SCA patients with hydroxyurea (HU) treatment (on-HU) and those without HU treatment (off-HU). We determine the shear viscosity of blood in health as well as in different states of disease. Our results suggest that treatment with HU improves or worsens the rheological characteristics of blood in SCA depending on the degree of hypoxia. However, on-HU groups always have higher levels of haematocrit-to-viscosity ratio (HVR) than off-HU groups, indicating that HU can indeed improve the oxygen transport potential of blood. Our patient-specific computational simulations suggest that the HVR level, rather than the shear viscosity of sickle RBC suspensions, may be a more reliable indicator in assessing the response to HU treatment.

Keywords: blood rheology; dissipative particle dynamics; hydroxyurea; sickle-cell anaemia.

Figure 1.

(a) Shear viscosity of healthy blood at Hct = 45% and (b) sickle RBC suspensions at Hct = 40% with different cell morphology. For comparison, the experimental measured shear viscosity of whole blood in health at Hct = 45% by Chien et al. [34] and in SCA at Hct = 40% by Kaul et al. [4], and previous computational simulations of sickle RBC suspensions at Hct = 40% by Lei et al. [23] are shown in these figures. The dashed line in panel (a) represents the fitted curve to the simulation result by , where is the shear rate; a, b and c are 6.6 × 10⁻³, −2374.7 and 2378.0, respectively. (Online version in colour.)

Figure 2.

Functional dependence of shear viscosity of sickle RBC suspensions on the normalized shear modulus obtained from DPD simulations.

Figure 3.

(a) sickle RBCs separated by different cell densities. Sickle blood is separated into four major cell subpopulations (fractions I–IV, SS1–SS4). (b) Typical shapes of sickle RBCs at each subpopulation under Oxy and DeOxy states. A1–A4 show sickle RBCs in fractions SS1–SS4 under Oxy state respectively; most cells have a discoid morphology. B1–B4 show sickle RBCs in fractions SS1-SS4 under DeOxy state respectively; a large percentage of cells appear to be granular and classic sickle morphology. (Online version in colour.)

Figure 4.

Predicted shear viscosity of blood in SCA at fully Oxy state (a), short-term DeOxy state (b) and long-term DeOxy state (c). The dark grey, grey and light grey columns show the viscosity values at shear rate , 80.0 and 140.0 s^–1, respectively. (Online version in colour.)

Figure 5.

Predicted HVR values of blood in SCA at fully Oxy state (a), short-term DeOxy state (b) and long-term DeOxy state (c). The dark grey, grey and light grey columns show the viscosity values at shear rate , 80.0 and 140.0 s^–1, respectively. (Online version in colour.)