The interaction of alpha-thalassemia and homozygous sickle-cell disease

Patients with homozygous sickle-cell disease may be homozygous for alpha-thalassemia 2 (O-/O-), may be heterozygous for alpha-thalessemia 2 (O-/OO), or may have a normal alpha-globin-gene complement (OO/OO). We compared the clinical and hematologic features of 44 patients who had sickle-cell disease and homozygous alpha-thalassemia 2 with those of controls with the two hematologic conditions. The patients with homozygous alpha-thalassemia 2 had significantly higher red-cell counts and levels of hemoglobin and hemoglobin Aý, as well as significantly lower hemoglobin F, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, mean corpuscular volume, reticulocyte counts, irreversibly-sickled-cell counts, and serum total billirubin levels, than those with a normal alpha-globin-gene complement. Heterozygotes (O-/OO) had intermediate values. In the group with homozygous alpha-thalassemia 2, fewer patients had episodes of acute chest syndrome and chronic leg ulceration and more patients had splenomegaly, as compared with patients in the other two subgroups. These data confirmed previous suggestions that alpha-thalassemia inhibits in vivo sickling in homozygous sickle-cell disease and may be an important genetic determinant of its hematologic severity.

The development of haematological changes in homozygous sickle cell disease: a cohort study from birth to 6 years

A cohort study of sickle cell disease from birth has allowed observations on the disease without the symptomatic selection inherent in previous series. The development of haematological indices from birth to 6 years in male and female infants with homozygous sickle cell (SS) disease is presented and compared with values in age and sex matched controls with a normal haemoglobin (AA) genotype previously presented elsewhere. In SS disease total haemoglobin levels fell rapidly from birth to a plateau at 3-6 months before falling again to 15 months after which no age related change occured. Mean cell haemoglobin concentration fell from birth to lowest values at 15-18 months before increasing to reach the level present at birth by the age of 5 years. Red cell counts fell rapidly after birth to a plateau at 2 months, increased slightly to 2 months and then fell steadily throughout the remaining period of study. The mean cell voloume and mean cell haemoglobin also fell rapidly after birth reaching the lowest values by 6 months and then increased progressively. Female patients showed significantly higher haemoglobin levels from 15 months to 4« years. Compared to AA controls, SS patients manifested significantly lower levels of haemoglobin from 2 weeks, and red cell counts from 1 month, and significantly higher levels of MCHA from 4 months to 3 years, MCV from 8 months to 5 years, and serum iron levels from 1 to 4 years. Children with SS disease were partially protected from iron deficiency in early childhood, perhaps by increased intestinal absorption of iron, and the associated increase in intracellular haemoglobin concentration might be disadvantageous during this high risk period (Summary)