Pathogenesis of Hemolytic Anemia in Homozygous Hemoglobin C Disease*

Abstract

Abstract. Hemoglobin C is less soluble than hemoglobin A in red cells, in hemolysates, and in dilute phosphate buffer. Its relative insolubility may be explained by electrostatic interactions between positively charged f36-lysyl groups and negatively charged groups on adjacent molecules. Red cells from patients with homozygous hemoglobin C (CC) disease exhibit aberrant physical properties which suggest that the cells are more rigid than normal erythrocytes. They pass through membrane filters less readily than normal red cells do, and their viscosity is higher than that of normal cells. Differences from normal cells are exaggerated if mean corpuscular hemoglobin concentration (MCHC) is increased, by suspension in hypertonic salt solution. Increased rigidity of CC cells, by accelerating their fragmentation, may be responsible for formation of microspherocytes. These small dense cells are exceptionally rigid, and probably are even more susceptible to fragmentation and sequestration. Rigidity of CC cells can be attributed to a "precrystalline" state of intracellular hemoglobin, in which crystallization does not occur, although the MCHC exceeds the solubility of hemoglobin in hemolysates.

Hemoglobin CC disease: rheological properties of erythrocytes and abnormalities in cell water

“…The hematological data for the nine patients studied are shown in Table I. In this study the mean corpuscular volume (MCV) is smaller and the mean corpuscular hemoglobin concentration (MCHC) is greater than reported previously (12). These differences probably are the result of determining the hematocrit by the microhematocrit method with centrifugation for 10 min, in contrast to the usual Wintrobe hematocrit (12).…”

“…The increased viscosity and decreased deformability of erythrocytes containing Hb CC suggests that the spleen sequesters these cells on the basis of the abnormal rheological properties. Increased viscosity and decreased filtration of Hb CC blood has also been described by Conley and Charache (11), and attributed to a "precrystalline" state of the intracellular HI) (12).…”

Association of hemoglobin C with erythrocyte ghosts.

“…The oxygen equilibria of dilute solutions of both hemoglobins are normal, including reactivity toward 2,3-diphosphoglycerate and CO2 (1). Both hemoglobins C and S are less soluble than normal hemoglobins and are known to polymerize readily (2). The solubility of Hb S decreases on deoxygenation, resulting in intracellular fiber formation and changes in the erythrocyte shape (sickling) (3).…”

Analysis of factors regulating erythrocyte deformability.

“…They never actually deformed to produce the characteristic elliptical diffraction pattern. At higher dextran concentrations of [15][16][17][18][19][20][21][22][23][24][25] g/100 ml PBS, the cells deformed over the entire shear stress range, with increasing deformation in the more viscous solutions for a given shear rate. However, even in 15 g/100 ml dextran (10.2 cp viscosity), the older, most dense 10% of normal cell populations did not deform appreciably.…”