Hemoglobin S and Sickling Disorders

The symptoms of sickle cell anemia are due to sequestration and destruction of the abnormal, sickled erythrocytes in the spleen and to the inability of many sickled 

Some of the clinical consequences in SS disease include megaloblastic erythropoiesis, aplastic crisis, stroke, bone pain crisis, proneness to infection particularly by Pneumococcus, Salmonella, and Haemophilus due to hypos-plenism and acute chest syndrome. Prophylactic use of penicillin and antipneumococcal and Haemophilus vaccines has aided in the management of life-threatening infectious complications of SS disease. Neonatal screening has been used in the identification of infants with sickle cell disease so that risk of infection can be modulated by appropriate immunizations and penicillin prophylaxis. The acute chest syndrome characterized by chest pain is due to clogged pulmonary capillaries in a small number of studies, patients have been treated with inhaled nitric oxide, which dilates blood vessels with clinical improvement. 

Individuals heterozygous for HbS and HbO Arab or HbD Los Angeles have a hemolytic anemia of a severity 

Understanding of the sickling process and of the structure of the HbS polymer provides a rational basis for ways of correcting the molecular defect. Thus, dilution of the HbS in the red cells, blockage of the interaction of the y86 valine with the hydrophobic pocket, and decrease of 

Structure of hemoglobin S (HbS) polymer. The valine at the j66 position of the deoxy-HbS fits into the hydrophobic pocket formed by leucine and phenylalanine at jS85 and j688 of an adjacent chain. Since each chain has an acceptor pocket and a donor valine, the HbS polymer has a double-stranded, half-staggered structure. [Reproduced with permission from S. Charache, Advances in the understanding of sickle cell anemia. Hasp. Pract. 21(2), 173 (1986). J. E. Zupko, illustrator.] 

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