Changes in the Structure and Function of the Red Cell Membrane Skeleton and Hemolytic Anemias

Abstract

This chapter reviews three molecular defects of the red cell membrane skeleton. In all three cases, the immediate cause of hemolysis are the abnormalities of skeletal protein interactions. However, only in one case, the primary cause of hemolysis is a hereditary defect of a molecule of the membrane skeleton, while in the other two cases the skeletal defect is either potentiated by an acquired disorder or caused by a mutation in the hemoglobin molecule. The first case reviewed is a strictly hereditary defect of the skeleton: A mutation of the protein spectrin which is expressed clinically as a severe elliptocytic hemolytic anemia. The second one involves a combination of an inherited spectrin defect with an acquired circulatory disorder which manifests as a severe life-threatening hemolytic anemia. Finally, an example is given of a defect in skeletal protein interactions which is not caused by mutations of skeletal proteins. In this case, irreversible hemichromes, the final products of intracellular hemoglobin denaturation, were found to release hemin which decreases the skeletal stability by weakening the spectrin-protein 4.1-actin interaction.