Effects of α‐thalassemia‐2 on the developmental changes of hematological values in children with sickle cell disease from georgia

A. E. Felice, K. M. McKie, M. P. Cleek, E. M. Marino, Abdullah Kutlar, V. C. McKie

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

The hematology and pathophysiology of sickle cell disease during the postnatal development of younger hemoglobin (Hb) S homozygotes (SS) could be considerably affected by a variability of α globin gene numbers. We have documented longitudinal developmental changes of hematological values and hemoglobin composition on 147 patients with SS (αα/αα), 64 with SS (‐α/αα), and 9 with SS (–α/–α) between the ages of 1 and 15 years. Non‐steady‐state data were excluded from these analyses. The number and organization of α globin genes was established by gene mapping. As anticipated, mean corpuscular volume and erythrocyte counts correlated with α globin gene numbers throughout the 15‐year age interval. On the other hand, SS children with αα/αα, –α/, –α had similar hemoglobin concentrations up to the ages of 5–10 years. Around the age of 7, the SS patients with –α/–α developed a higher Hb concentration than that of the SS (–α/αα), which in turn was higher than that of the SS (αα/αα). The emergence of this difference coincided with a developmental increase of the mean corpuscular hemoglobin concentration (MCHC) in patients with SS (αα/αα) and the decline of Hb F % under 15%. This newly observed developmental change of the MCHC could lead to increased hemolysis and anemia after the age of 5‐10 years. It occurs to a smaller extent among SS (–α/αα) or not at all among SS (–α/αα) such that these two categories of patients have less severe hemolysis and higher hemoglobin levels at older ages. Although the proportion of Hb F was independent of α globin gene numbers, the absence of Hb Bart's suggested that α‐thalassemia promotes the intracellular assembly of Hb F over Hb S tetramers. Thus, the interaction of α‐thalassemia and Hb F in young SS patients may be more complex than revealed by Hb F levels in cell lysates. Among older SS children (> 7 years) α‐thalassemia and Hb F levels exceeding 15% appear to have additive effects in diminishing the rate of hemolysis.

Original languageEnglish (US)
Pages (from-to)389-400
Number of pages12
JournalAmerican Journal of Hematology
Volume25
Issue number4
DOIs
StatePublished - Jan 1 1987

Fingerprint

Fetal Hemoglobin
Sickle Cell Anemia
Globins
Sickle Hemoglobin
Erythrocyte Indices
Thalassemia
Hemolysis
Hemoglobins
Genes
Erythrocyte Count
Chromosome Mapping
Homozygote
Hematology
Anemia

Keywords

  • anemia
  • fetal hemoglobin
  • hemoglobinopathy
  • red cell indices
  • α‐globin genes

ASJC Scopus subject areas

  • Hematology

Cite this

Effects of α‐thalassemia‐2 on the developmental changes of hematological values in children with sickle cell disease from georgia. / Felice, A. E.; McKie, K. M.; Cleek, M. P.; Marino, E. M.; Kutlar, Abdullah; McKie, V. C.

In: American Journal of Hematology, Vol. 25, No. 4, 01.01.1987, p. 389-400.

Research output: Contribution to journalArticle

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abstract = "The hematology and pathophysiology of sickle cell disease during the postnatal development of younger hemoglobin (Hb) S homozygotes (SS) could be considerably affected by a variability of α globin gene numbers. We have documented longitudinal developmental changes of hematological values and hemoglobin composition on 147 patients with SS (αα/αα), 64 with SS (‐α/αα), and 9 with SS (–α/–α) between the ages of 1 and 15 years. Non‐steady‐state data were excluded from these analyses. The number and organization of α globin genes was established by gene mapping. As anticipated, mean corpuscular volume and erythrocyte counts correlated with α globin gene numbers throughout the 15‐year age interval. On the other hand, SS children with αα/αα, –α/, –α had similar hemoglobin concentrations up to the ages of 5–10 years. Around the age of 7, the SS patients with –α/–α developed a higher Hb concentration than that of the SS (–α/αα), which in turn was higher than that of the SS (αα/αα). The emergence of this difference coincided with a developmental increase of the mean corpuscular hemoglobin concentration (MCHC) in patients with SS (αα/αα) and the decline of Hb F {\%} under 15{\%}. This newly observed developmental change of the MCHC could lead to increased hemolysis and anemia after the age of 5‐10 years. It occurs to a smaller extent among SS (–α/αα) or not at all among SS (–α/αα) such that these two categories of patients have less severe hemolysis and higher hemoglobin levels at older ages. Although the proportion of Hb F was independent of α globin gene numbers, the absence of Hb Bart's suggested that α‐thalassemia promotes the intracellular assembly of Hb F over Hb S tetramers. Thus, the interaction of α‐thalassemia and Hb F in young SS patients may be more complex than revealed by Hb F levels in cell lysates. Among older SS children (> 7 years) α‐thalassemia and Hb F levels exceeding 15{\%} appear to have additive effects in diminishing the rate of hemolysis.",
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N2 - The hematology and pathophysiology of sickle cell disease during the postnatal development of younger hemoglobin (Hb) S homozygotes (SS) could be considerably affected by a variability of α globin gene numbers. We have documented longitudinal developmental changes of hematological values and hemoglobin composition on 147 patients with SS (αα/αα), 64 with SS (‐α/αα), and 9 with SS (–α/–α) between the ages of 1 and 15 years. Non‐steady‐state data were excluded from these analyses. The number and organization of α globin genes was established by gene mapping. As anticipated, mean corpuscular volume and erythrocyte counts correlated with α globin gene numbers throughout the 15‐year age interval. On the other hand, SS children with αα/αα, –α/, –α had similar hemoglobin concentrations up to the ages of 5–10 years. Around the age of 7, the SS patients with –α/–α developed a higher Hb concentration than that of the SS (–α/αα), which in turn was higher than that of the SS (αα/αα). The emergence of this difference coincided with a developmental increase of the mean corpuscular hemoglobin concentration (MCHC) in patients with SS (αα/αα) and the decline of Hb F % under 15%. This newly observed developmental change of the MCHC could lead to increased hemolysis and anemia after the age of 5‐10 years. It occurs to a smaller extent among SS (–α/αα) or not at all among SS (–α/αα) such that these two categories of patients have less severe hemolysis and higher hemoglobin levels at older ages. Although the proportion of Hb F was independent of α globin gene numbers, the absence of Hb Bart's suggested that α‐thalassemia promotes the intracellular assembly of Hb F over Hb S tetramers. Thus, the interaction of α‐thalassemia and Hb F in young SS patients may be more complex than revealed by Hb F levels in cell lysates. Among older SS children (> 7 years) α‐thalassemia and Hb F levels exceeding 15% appear to have additive effects in diminishing the rate of hemolysis.

AB - The hematology and pathophysiology of sickle cell disease during the postnatal development of younger hemoglobin (Hb) S homozygotes (SS) could be considerably affected by a variability of α globin gene numbers. We have documented longitudinal developmental changes of hematological values and hemoglobin composition on 147 patients with SS (αα/αα), 64 with SS (‐α/αα), and 9 with SS (–α/–α) between the ages of 1 and 15 years. Non‐steady‐state data were excluded from these analyses. The number and organization of α globin genes was established by gene mapping. As anticipated, mean corpuscular volume and erythrocyte counts correlated with α globin gene numbers throughout the 15‐year age interval. On the other hand, SS children with αα/αα, –α/, –α had similar hemoglobin concentrations up to the ages of 5–10 years. Around the age of 7, the SS patients with –α/–α developed a higher Hb concentration than that of the SS (–α/αα), which in turn was higher than that of the SS (αα/αα). The emergence of this difference coincided with a developmental increase of the mean corpuscular hemoglobin concentration (MCHC) in patients with SS (αα/αα) and the decline of Hb F % under 15%. This newly observed developmental change of the MCHC could lead to increased hemolysis and anemia after the age of 5‐10 years. It occurs to a smaller extent among SS (–α/αα) or not at all among SS (–α/αα) such that these two categories of patients have less severe hemolysis and higher hemoglobin levels at older ages. Although the proportion of Hb F was independent of α globin gene numbers, the absence of Hb Bart's suggested that α‐thalassemia promotes the intracellular assembly of Hb F over Hb S tetramers. Thus, the interaction of α‐thalassemia and Hb F in young SS patients may be more complex than revealed by Hb F levels in cell lysates. Among older SS children (> 7 years) α‐thalassemia and Hb F levels exceeding 15% appear to have additive effects in diminishing the rate of hemolysis.

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