Defective spectrin dimer self‐association in thalassemic red cells

Abstract

The relative proportions of spectrin tetramer and dimer forms extrated from red cell membranes in a low ionic strength buffer at 4°C were determined for 15 normal subjects, 27 subjects with α‐thalassemia (7 α‐thalassemia trait, 9 Hb H disease (α‐thal 1/α‐thal 2) and 11 Hb H with Hb Constant Spring (CS), 23 subjects with β‐thalassemia (6 β‐thalassemia trait, 5 homozygous β‐thalassemia, 11 β°‐thalassemia with Hb E and 1 β +‐thalassemia with Hb E), 6 subjects with Hb E (2 homozygous and 4 carriers) and 1 subject with combined α‐thal 1/Hb CS and Hb E (AE Bart's disease). In all subjects (except carriers of Hb E and 1 splenectomized case of β°‐thal/Hb E) spectrin dimer forms were elevated when compared to levels in normal controls, but there were no significant differences between carrier and disease forms. Conversion of spectrin dimers to tetramers at 30° C was reduced in the thalassemic subjects with disease but was within normal range for thalassemic carriers.

Donor‐variation effect on red blood cell storage lesion: A close relationship emerges

“…On one hand, lower production of functional Hb and slight excess of soluble alpha-globin chains in Tm-RBCs lead to low Hb concentration, slightly enhanced hemolysis and oxidative stress and a cascade of directly or indirectly associated changes [70] including membrane loss, impaired rheology [71], defective spectrin self-association [72], aberrant binding of Hb to skeletal components, cellular dehydration, membrane rigidity [73], or defected deformability [74], increased band 3 phosphorylation [75] and caspase-3 activation [76], which exposes band 3 to increased risk of proteolysis [77]. Membrane remodeling [70] and aberrant activity of membrane pumps and transporters [78] lead to loss of band 3 metabolic modulation, depletion of energy sources, senescence and signaling of RBC removal.…”