Abnormal rheology of oxygenated blood in sickle cell anemia

Abstract

A B S T R A C T The viscosity of oxygenated blood from patients with sickle cell anemia (Hb SS disease) was found to be abnormally increased, a property which contrasts with the well recognized viscous aberration produced by deoxygenation of Hb SS blood. Experiments designed to explain this finding led to considerations of deformation and aggregation, primary determinants of the rheologic behavior of erythrocytes as they traverse the microcirculation. Deformability of erythrocytes is in turn dependent upon internal viscosity (i.e. the state and concentration of hemoglobin in solution) and membrane flexibility. Definition of the contribution made by each of these properties to the abnormal viscosity of oxygenated Hb SS blood was made possible by analysis of viscosity measurements, made over a wide range of shear rates and cell concentrations, on Hb SS erythrocytes and normal erythrocytes suspended in Ringer's solution (where aggregation does not occur) and in plasma. Similar

Red blood cell aggregation, aggregate strength and oxygen transport potential of blood are abnormal in both homozygous sickle cell anemia and sickle-hemoglobin C disease

“…This abnormal rheological behavior is primarily due to the elevated internal viscosity of irreversibly sickled cells and the reduced membrane flexibility of both irreversibly and transiently sickled cells. 2 Our finding of reduced RBC deformability in the SCC group confirms previous data by Ballas et al and may be explained by the presence of severely dehydrated, microcytic and hyperchromic RBC. 1,16 Note that, on average, RBC deformability for the SCC group was slightly better than for SCA patients at both shear stresses.…”

“…5 However, since γmin for SCA and SCC patients were similar, differences of blood viscosity and RBC deformability between the two groups probably play a role in their unequal clinical severity. 26 Although the forces required to disperse preformed RBC aggregates are elevated in SCA and SCC subjects, the extent of aggregation at stasis (i.e., AI) was lower than control in both groups; this finding contrasts with results obtained by Obiefuna et al 27 on SCA patients but is consistent with results obtained by Chien et al 2 The reasons for the discordant results for aggregation at stasis remain unknown, but may be due to different experimental methods: in the current study defined preshearing of blood samples to disperse pre-existing aggregates was employed whereas it was not part of the microscopic method used by Obiefuna et al 27 Note that the present results indicate that time for formation of RBC aggregates is increased in SCA and SCC patients ( Table 3), meaning that the formation of branched 3-dimension aggregates is slower in these subjects. The effects of RBC aggregation on in vivo flow dynamics and flow resistance are complex 5,28 and further studies are warranted to better understand the association between RBC aggregation parameters and the severity of sickle cell disease.…”

“…Although we did not investigate the percent of irreversibly sickled cells (ISC), their presence, in combination with individually variable Hct levels, can markedly affect blood viscosity and the occurrence of vaso-occlusive manifestations. 2,18 Interestingly, our results showed that, except for the lowest shear rate, blood viscosity of AS subjects was similar to that of the SCC group. This is a surprising result because AS is usually considered a benign condition, 19 except when these individuals are subject to stressful conditions such as altitude hypoxia or extreme exercise.…”

“…[1][2][3] When deoxygenated in certain areas of the circulatory system, these rigid, distorted RBC can prompt vascular occlusions leading to painful crises. Although the genetic mutation is well described and is universal in all patients with SCA, the clinical severity and complications of the disease show significant interindividual variability.…”

Microfluidic analysis of cellular deformability of normal and oxidatively damaged red blood cells

“…Successful transit of these anatomical structures is dependent upon the deformability of the RBC. Cellular deformability is a function of its surface to volume ratio, cytoplasmic viscosity, and membrane viscoelasticity [6][7][8][9][10]. Biological, pharmacological or biochemical changes that affect any of these variables can contribute to loss of cellular deformability and the premature clearance of the RBC via capillary or splenic sequestration, phagocytosis or intravascular lysis [3,[11][12][13][14][15][16].…”