Alpha thalassemia and the hematology of homozygous sickle cell disease in childhood

Abstract

alpha Thalassemia modifies the hematologic expression of homozygous sickle cell (SS) disease, resulting in increased total hemoglobin and HbA2 and decreased HbF, mean cell volume, reticulocytes, irreversibly sickled cells, and bilirubin levels. The age at which these changes develop in children with SS disease is unknown. Ascertainment of globin gene status in a large representative sample of children with SS disease has afforded an opportunity to study the hematologic indices in nine children homozygous for alpha thalassemia 2 (two-gene group), 90 children heterozygous for alpha thalassemia 2 (three-gene group), and 167 children with a normal alpha globin gene complement (four-gene group). The two-gene group had significantly lower mean cell volumes from birth, higher red cell counts from one month, lower reticulocytes from three months, and higher HbA2 levels from one year, as compared with the four-gene group. Children with three genes had intermediate indices but resembled more closely the four-gene group. Differences in total hemoglobin or in fetal hemoglobin between the groups were not apparent by eight years of age. The most characteristic differences of the two-gene group were the raised proportional HbA2 level and low mean cell volume, the latter having some predictive value for alpha thalassemia status at birth.

Molecular analysis and association with clinical and laboratory manifestations in children with sickle cell anemia

“…Hb values did not differ between the groups with or without alpha-thalassemia, similar to the results reported by Silva Filho et al 11 and Stevens et al 23 Significant reductions in MCV and MCH levels and reticulocyte counts, and a significant increase in the RBC count in α3.7 deletion patients confirms data in the literature. 2,17,22 There was no statistically significant difference in the WBC count between the groups, contrary to other publications that reported a reduction in the WBC count in individuals with alpha-thalassemia.…”

“… 18,21 The presence of alpha-thalassemia is also significantly associated with a reduction in white blood cell (WBC) 15 and reticulocyte 2,17 counts, and increased levels of Hb A 2 . 17,22–25 Although there is no defined relationship, increased levels of Hb F are also reported. 2,24 …”

Haptoglobin, alpha‐thalassaemia and glucose‐6‐phosphate dehydrogenase polymorphisms and risk of abnormal transcranial Doppler among patients with sickle cell anaemia in Tanzania

“…Although the co‐inheritance of α‐thalassaemia deletions and glucose‐6‐phosphate dehydrogenase (G6PD) deficiency have been previously investigated as disease modifiers in SCA, specifically affecting risk of elevated CBFv and/or stroke, these have not been investigated in Africa. The co‐inheritance of alpha‐thalassaemia in SCA modifies red cell indices (Embury et al , ; Stevens et al , ; Kulozik et al , ) and red cell rheology (Serjeant et al , ), and, in some reports, increases total Hb (Embury et al , ). Alpha‐thalassaemia is consistently associated with a decreased risk of increased CBFv and/or stroke in SCA (Adams et al , ; Hsu et al , ; Bernaudin et al , ; Belisario et al , ; Flanagan et al , ).…”

Jamaica and Research in Sickle Cell Disease

“…The midwives of VJH were superb, and over the next eight and a half years, ending on December 28, 1981, a total of 100 000 non-operative deliveries were screened with the detection of 550 babies with forms of sickle cell disease (54). The first 125 patients with an SS phenotype were matched by age and gender to two controls with normal AA phenotype providing 250 controls, and the entire 800 subjects have been followed up over Jamaica has been fortunate in collaboration with groups abroad such as David Weatherall and Douglas Higgs in Oxford and with Johns Hopkins Hospital, especially George Dover, which have increased the understanding of molecular changes modifying expression of the disease (94)(95)(96)(97)(98)(99)(100)(101)(102)(103)(104)(105)(106)(107). The evolution of ocular pathology in Cohort subjects was carefully documented from 1980 to 2000 by Alan Bird from Moorfields Eye Hospital in London who, with Mrs Sarah Bird, led a team of four to five ophthalmologists who volunteered their services for two to three weeks each year.…”