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

Felice, Alex E.; McKie, Kathleen T.; Cleek, M. P.; Mariño, Eliana; Kutlar, Abdullah; McKie, Virgil

doi:10.1002/ajh.2830250405

Cited by 21 publications

(11 citation statements)

References 19 publications

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“…This concurs with some studies (16,41) but not with others (6)(7)(8)10,12,13,34,38,40,43). This divergence can be explained by the difference in age of the subjects across studies.…”

Section: Discussionsupporting

confidence: 92%

“…This divergence can be explained by the difference in age of the subjects across studies. It is possible that the difference in total Hb will emerge as these indices stabilize in older children, and therefore could not be detected in the present study (7,41). There was no significant difference in the mean levels of Hb F among the groups with different α-globin genotypes.…”

Section: Discussionmentioning

confidence: 78%

“…This is probably due to the reduction in the hemolytic rate (7,10,42), irreversibly sickled cells (6,14), as well as a possible decrease in inflammatory process. Also in concurrence with other studies, the mean levels of MCV (6)(7)(8)10,12,13,15,16,23,34,38,41,43,44) and MCH (6,8,15,23,43,44) were significantly lower in subjects with α-thal. This is due to the reduction in the synthesis of α chains (45).…”

Section: Discussionmentioning

confidence: 99%

“…α-Thalassemia reduces intraerythrocytic Hb S [β6(A3)Glu→Val, GAG>GT G] concentration, which reduces hemoglobin (Hb) polymerization and intensity of hemolysis leading to clinical and laboratory outcomes that might be beneficial or prejudicial (5). As to laboratory features, the coexistence of α-thal increases the number of red blood cells, total Hb levels and packed cell volume (PCV) and decreases the levels of mean corpuscular volume (MCV), mean corpuscular Hb (MCH), mean corpuscular Hb concentration (MCHC) (6)(7)(8)(9)(10), reticulocyte count (10)(11)(12), white blood cell count (WBC) (8,10,13) and irreversibly sickled cells (6,14). Coexistence of α-thal apparently increases Hb A 2 levels in sickle cell anemia (8,13,15) and does not influence Hb F levels (9,15,16).…”

Section: Introductionmentioning

confidence: 99%

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Coinheritance of α-Thalassemia Decreases the Risk of Cerebrovascular Disease in a Cohort of Children with Sickle Cell Anemia

et al. 2010

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The study estimated α-thalassemia (α-thal) prevalence and assessed its associations with clinical and hematological features in a random sample of Brazilian children with sickle cell anemia (208 Hb SS and 13 Hb S-β⁰-thal). α-Thalassemia genotyping was carried out by multiplex polymerase chain reaction (m-PCR) for seven alleles. Clinical and hematological data were retrieved from the 221 children's medical files. Their ages ranged from 2.5 to 10.4 years. Of the Hb SS children, 27.9% carried -α(3.7)/αα and 1.4% -α(3.7)/-α(3.7). The presence of α-thal was significantly associated with reduction in MCV, MCH, WBC values and reticulocyte counts. No significant association with blood transfusion or acute chest syndrome (ACS), was found. α-Thalassemia genotypes were strongly associated with reduction in risk for cerebrovascular disease (CVD) (conditional and abnormal transcranial Doppler or stroke; p = 0.007). The interaction of α-thal with other modulating factors should be investigated in order to define subphenotypes of the disease and to use them as clinical tools in the follow-up care of patients.

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“…This concurs with some studies (16,41) but not with others (6)(7)(8)10,12,13,34,38,40,43). This divergence can be explained by the difference in age of the subjects across studies.…”

Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Coinheritance of α-Thalassemia Decreases the Risk of Cerebrovascular Disease in a Cohort of Children with Sickle Cell Anemia

et al. 2010

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“…Investigators often calculate aver ages of groups of values, but the large standard deviations preclude a definitive evaluation of differences that might exist [17]. We elected to provide the individual values as computer-generated printouts leaving an evaluation of the significance of this information to the reader.…”

Section: Discussionmentioning

confidence: 99%

Level of Fetal Hemoglobin in Children with Sickle Cell Anemia Influence of Gender, Haplotype and α-Thalassemia-2 Trait

Adekile

Huisman²

1993

Acta Haematol

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We have evaluated hematological data for numerous blood samples collected from 51 sickle cell anemia (SS) patients during their first 10 years of life. Haplo-types and α-globin gene status were determined in all patients. A total of 482 hematological evaluations and 317 fetal hemoglobin (Hb F) determinations are presented. The data show that the Hb F levels are the highest in patients with haplotypes 3/3 and the lowest in those with haplotypes 20/20. This is reflected in differences in total hemoglobin, PCV value, and RBC counts, which are the lowest in the 20/20 group and the highest in the 3/3 group. Female SS patients with haplotypes 19/19 have higher Hb F levels than their male counterparts; the same was observed for the patients with the 19/3 haplotype combination but not for those with the 20/3 haplotype combination. A concomitant α-thalassemia-2 heterozygosity had little or no effect on the hemoglobin level. The data confirm that SS children, aged 1-10 years, with a homozygosity for haplotype No. 20 are most severely affected by their disease.

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Genetic Variation and Sickle Cell Disease Severity

Kirkham,

Estepp,

Weiss

et al. 2023

JAMA Netw Open

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ImportanceSickle cell disease (SCD) is a monogenic disorder, yet clinical outcomes are influenced by additional genetic factors. Despite decades of research, the genetics of SCD remain poorly understood.ObjectiveTo assess all reported genetic modifiers of SCD, evaluate the design of associated studies, and provide guidelines for future analyses according to modern genetic study recommendations.Data SourcesPubMed, Web of Science, and Scopus were searched through May 16, 2023, identifying 5290 publications.Study SelectionAt least 2 reviewers identified 571 original, peer-reviewed English-language publications reporting genetic modifiers of human SCD phenotypes, wherein the outcome was not treatment response, and the comparison was not between SCD subtypes or including healthy controls.Data Extraction and SynthesisData relevant to all genetic modifiers of SCD were extracted, evaluated, and presented following STREGA and PRISMA guidelines. Weighted z score meta-analyses and pathway analyses were conducted.Main Outcomes and MeasuresOutcomes were aggregated into 25 categories, grouped as acute complications, chronic conditions, hematologic parameters or biomarkers, and general or mixed measures of SCD severity.ResultsThe 571 included studies reported on 29 670 unique individuals (50% ≤ 18 years of age) from 43 countries. Of the 17 757 extracted results (4890 significant) in 1552 genes, 3675 results met the study criteria for meta-analysis: reported phenotype and genotype, association size and direction, variability measure, sample size, and statistical test. Only 173 results for 62 associations could be cross-study combined. The remaining associations could not be aggregated because they were only reported once or methods (eg, study design, reporting practice) and genotype or phenotype definitions were insufficiently harmonized. Gene variants regulating fetal hemoglobin and α-thalassemia (important markers for SCD severity) were frequently identified: 19 single-nucleotide variants in BCL11A, HBS1L-MYB, and HBG2 were significantly associated with fetal hemoglobin (absolute value of Z = 4.00 to 20.66; P = 8.63 × 10−95 to 6.19 × 10−5), and α-thalassemia deletions were significantly associated with increased hemoglobin level and reduced risk of albuminuria, abnormal transcranial Doppler velocity, and stroke (absolute value of Z = 3.43 to 5.16; P = 2.42 × 10−7 to 6.00 × 10−4). However, other associations remain unconfirmed. Pathway analyses of significant genes highlighted the importance of cellular adhesion, inflammation, oxidative and toxic stress, and blood vessel regulation in SCD (23 of the top 25 Gene Ontology pathways involve these processes) and suggested future research areas.Conclusions and RelevanceThe findings of this comprehensive systematic review and meta-analysis of all published genetic modifiers of SCD indicated that implementation of standardized phenotypes, statistical methods, and reporting practices should accelerate discovery and validation of genetic modifiers and development of clinically actionable genetic profiles.

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

Cited by 21 publications

References 19 publications

Coinheritance of α-Thalassemia Decreases the Risk of Cerebrovascular Disease in a Cohort of Children with Sickle Cell Anemia

Coinheritance of α-Thalassemia Decreases the Risk of Cerebrovascular Disease in a Cohort of Children with Sickle Cell Anemia

Level of Fetal Hemoglobin in Children with Sickle Cell Anemia Influence of Gender, Haplotype and α-Thalassemia-2 Trait

Genetic Variation and Sickle Cell Disease Severity

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