Hemorheological Alterations and Oxidative Damage in Sickle Cell Anemia

Abstract

Sickle cell anemia (SCA) is the most common hereditary disorder of hemoglobin (Hb) characterized by a mutation in the β globin gene, which leads to synthesis of HbS a hemoglobin which, under hypoxic conditions, gels and leading to the sickling of the red blood cells (RBC). The dehydration of the RBC increases the concentration of the intracellular Hb with an increase in the internal viscosity and consequently a decrease in the erythrocyte deformability. Sickle red blood cells due to their difficulty to flow through the microcirculation cause frequent vaso-occlusive episodes, tissue ischemia, and infarctions. Moreover, the reduced RBC deformability causes cell fragility leading to hemolysis and recently a key role of hemolysis and oxidative stress in the development of vascular dysfunction has been demonstrated. The aim of this study was to evaluate the hemorheological profiles of patients with SCA in order to point out new indices of vascular impairment, and to characterize the membrane oxidative damage of sickled RBC. Blood viscosities, erythrocyte aggregation, and viscoelastic profiles of SCA patients were determined, and the RBC oxidative damage was investigated by comparing metabolic capability and RBC membrane proteins from SCA patients with and without transfusion dependence. The hemorheological profile of SCA subjects demonstrated high blood viscosity, increased RBC aggregation, and decreased RBC deformability. These impaired flow properties were associated with RBC membrane protein oxidation, with degradation of spectrin and increased membrane-bound globin. The comparison between SCA patients with and without transfusion dependence showed metabolic and structural RBC oxidative damage significantly different.

The Worst Things in Life are Free: The Role of Free Heme in Sickle Cell Disease

“…Oxidative stress contributes to pathophysiological pathways that underlie inflammation in many hemolytic disorders including SCD ( 8 ), β-thalassemia ( 9 , 10 ), paroxysmal nocturnal hemoglobinuria ( 11 , 12 ), hereditary spherocytosis ( 13 ), and glucose-6-phosphate dehydrogenase deficiency ( 14 – 16 ). RBCs are constantly subjected to oxidative stress due to their role as an oxygen transporter and continuous exposure to both endogenous and exogenous sources of ROS that can damage the RBC and alter blood rheology in SCD patients ( 17 , 18 ). ROS is generated in SCD through several pathways.…”

Effects of red blood cells with reduced deformability on cerebral blood flow and vascular water transport: measurements in rats using time-resolved pulsed arterial spin labelling at 9.4 T

“…As a final clinical and translational outlook, one might mention that haemorheological abnormalities, particularly RBC deformability changes, have been shown to correlate with severe complications of several haematological diseases such as malaria, hereditary spherocytosis, diabetes mellitus and paroxysmal nocturnal haemoglobinuria [ 53 – 57 ]. Due to RBC dehydration, sickle cell disease is specifically associated with a decrease in erythrocyte deformability; due to impaired ability to flow through the microcirculation, sickle red blood cells tend thus to cause vascular occlusive episodes, ischemia and infarction [ 49 , 58 ]. Hence, in vivo techniques to monitor effects of impaired RBC deformability would be of interest, and ASL-based observations of the hemodynamic impact of mildly damaged RBCs are thus of potential relevance also from a clinical perspective.…”

Visualization and Measurements of Blood Cells Flowing in Microfluidic Systems and Blood Rheology: A Personalized Medicine Perspective

“…Hemorheology, the study of deformation and blood flow, have been more focused on RBC rheology, relating the deformation and aggregation of RBCs, since erythrocytes comprise the major components in blood. However, RBCs studies alone may not show the progress of the disease, thus complementary studies are needed, such as whole blood and plasma viscosity, RBC aggregation, deformability measurements, blood cells population count, and morphological analysis [ 1 , 2 , 3 , 4 , 5 , 6 , 7 ] must be integrated as to further develop an efficient point-of-care tool.…”

“…Lee et al, 2019 [ 6 ] have performed a review with the most recent clinical studies of diabetic kidney disease associated with hemorheological parameters, demonstrating that critical shear-rate and –stress, measured by a microfluidic aggregometry [ 6 ], aggregation index and RBC deformability elongation index, measured by a microfluidic ektacytometry [ 16 ], must be combined as a tool for a successful diagnosis of disease stage and possible derivate complications. Additionally, Caprari et al, (2019) [ 7 ] have demonstrated that blood viscosity and RBC aggregation increase with the decreasing of the RBCs deformability, by using blood samples from subjects with sickle cell anemia. However, no microfluidic technologies have been used in these studies.…”