Hemoglobinopathy testing: the significance of accuracy and pitfalls in HbA<sub>2</sub> determination

Wajcman, Henri; Azimi, Mahin; Cui, Jialing; Hoppe, Carolyn; Flamini, M.; Ho, Cha Sung; Reddy, Sahitya

doi:10.1111/ijlh.12584

Cited by 6 publications

(5 citation statements)

References 8 publications

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“…There may exist very significant associations between minor Hbs and psychiatric diseases, yet a majority of these conditions may be overlooked due to clinically/hematologically‐silent phenotypes and/or inadequate sensitivity of current detection methods. For instance, the most common Hb variants (Hb S and Hb C) present usually with normocytic indices (Wajcman et al, 2017). Low or borderline values HbA2 (3.2–3.9%) in a microcytic patient may not necessarily indicate iron depletion but also ‘normal HbA2 β‐thalassemia’ condition.…”

Section: Background: New Evidence Suggest That Hemoglobins (Hbs) Are mentioning

confidence: 99%

“…Iron deficiency does not lower the elevated value of the HbA2 in the classic carrier, yet it might mask normal HbA2 β‐thalassemia and α‐thalassemia conditions. Another possible masking can occur via a ‘normalization’ of the elevated HbA2 level due to various abnormalities of the δ‐globin genes, which are quite frequent in Mediterranean and Middle East populations (Wajcman et al, 2017). We conclude that exome‐sequencing of globin‐loci with next‐generation sequencing methods may provide obtaining the most sensitive and reliable results in illuminating globins’ roles in psychiatric diseases.…”

Section: Background: New Evidence Suggest That Hemoglobins (Hbs) Are mentioning

confidence: 99%

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Hemoglobins emerging roles in mental disorders. Metabolical, genetical and immunological aspects

Altinöz¹,

Ince

2017

Intl J of Devlp Neuroscience

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Hemoglobin (Hb) expression in the central nervous system is recently shown. Cooccurences of mental disorders (mainly bipolar disorder (BD) and tic disorders) with β- or α-thalassemia trait or erythrocytosis were witnessed, which may be due to peripheral or central hypoxia/hyperoxia or haplotypal gene interactions. β-Globin genes reside at 11p15.5 close to tyrosine hydroxylase, dopamine receptor DRD4 and Brain Derived Neurotrophic Factor, which involve in psychiatric diseases. α-Globin genes reside at 16p13.3 which associates with BD, tic disorders, ATR-16 Syndrome and Rubinstein Taybi Syndrome (RTS). CREB-Binding Protein (CEBBP)-gene is mutated in RTS, which commonly associates with mood disorders. 16p13.3 region also contains GRIN2A gene encoding N-methyl-d-aspartate receptor-2A and SSTR5 (Somatostatin Receptor-5), again involving in mental disorders. We demonstrated a protective role of minor HbA2 against post-partum episodes in BD and association of higher minor HbF (fetal hemoglobin) levels with family history of psychosis in a BD-patient cohort. HbA2 increases in cardiac ischemia and in mountain dwellers indicating its likely protection against ischemia/hypoxia. HMGIY, a repressive transcription factor of δ-globin chain of HbA2 is increased in lymphocytes of schizophrenics. In autism, deletional mutations were found in BCL11A gene, which cause persistence of HbF at high levels in adulthood. Also, certain polymorphisms in BCL11A strongly associate with schizophrenia. Further, many drugs from anabolic steroids to antimalarial agents elevate HbF and may cause mania. We ascribe a protective role to HbA2 and a maladaptive detrimental role to HbF in psychopathology. We believe that future studies on hemoglobins may pave to discover novel pathogenesis mechanisms in mental disorders.

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Section: Background: New Evidence Suggest That Hemoglobins (Hbs) Are mentioning

confidence: 99%

Section: Background: New Evidence Suggest That Hemoglobins (Hbs) Are mentioning

confidence: 99%

Hemoglobins emerging roles in mental disorders. Metabolical, genetical and immunological aspects

Altinöz¹,

Ince

2017

Intl J of Devlp Neuroscience

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“…Various genetic and acquired factors are known to be associated with borderline HbA 2 , and values above 3.2 require DNA analysis for further investigation. The presence of sickle Hb (HbS) can lead to falsely elevated HbA 2 levels in most high performance liquid chromatography (HPLC) systems [32]. Severe iron deficiency, on the other hand, can reduce HbA 2 levels by up to 0.5% [31].…”

Section: How Screening and Early Detection Can Prevent Thalassemia?mentioning

confidence: 99%

Thalassemia in the laboratory: pearls, pitfalls, and promises

Aliyeva¹,

Asadov²,

Mammadova³

et al. 2018

Clinical Chemistry and Laboratory Medicine (CCLM)

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Thalassemia is one of the most common hereditary disorders of the developing world, and it is associated with severe anemia and transfusion dependence. The global health burden of thalassemia has increased as a result of human mobility and migration in recent years. Depending on inherited mutations, thalassemia patients exhibit distorted hemoglobin (Hb) patterns and deviated red cell indices, both of which can be used to support identification by diagnostic tools. Diagnostic approaches vary depending on the target population and the aim of the testing. Current methods, which are based on Hb patterns, are used for first-line screening, whereas molecular testing is needed for conformation of the results and for prenatal and preimplantation genetic diagnosis. In the present paper, we review the diagnostic parameters, pitfalls, interfering factors, and methods; currently available best-practice guidelines; quality assurance and standardization of the procedures; and promising laboratory technologies for the future of thalassemia diagnosis.

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“…Considering the small percentage differences that may exist between normal and pathological Hb A 2 values, high precision in the measurement of this important parameter is required. There are several methods for testing Hb A 2 , but the two most widely used are automated high-performance liquid chromatography (HPLC) and capillary electrophoresis (CE) [4,5]. The differences between the available commercial separation methods have still proven to be significant, even though the use of switchable control materials can halve the variability between methods [6].…”

Section: Introductionmentioning

confidence: 99%

Hemoglobin A2 and Heterogeneous Diagnostic Relevance Observed in Eight New Variants of the Delta Globin Gene

Mahmud

Maffei

Mogni

et al. 2021

Genes

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Background: Hemoglobin A (Hb A) (α2β2) in the normal adult subject constitutes 96–98% of hemoglobin, and Hb F is normally less than 1%, while for hemoglobin A2 (Hb A2) (α2δ2), the normal reference values are between 2.0 and 3.3%. It is important to evaluate the presence of possible delta gene mutations in a population at high risk for globin gene defects in order to correctly diagnose the β-thalassemia carrier. Methods: The most used methods for the quantification of Hb A2 are based on automated high performance liquid chromatography (HPLC) or capillary electrophoresis (CE). In particular Hb analyses were performed by HPLC on three dedicated devices. DNA analyses were performed according to local standard protocols. Results: Here, we described eight new δ-globin gene variants discovered and characterized in some laboratories in Northern Italy in recent years. These new variants were added to the many already known Hb A2 variants that were found with an estimated frequency of about 1–2% during the screening tests in our laboratories. Conclusions: The knowledge recognition of the delta variant on Hb analysis and accurate molecular characterization is crucial to provide an accurate definitive thalassemia diagnosis, particularly in young subjects who would like to ask for a prenatal diagnosis or preimplantation genetic diagnosis.

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Hemoglobinopathy testing: the significance of accuracy and pitfalls in HbA₂ determination

Cited by 6 publications

References 8 publications

Hemoglobins emerging roles in mental disorders. Metabolical, genetical and immunological aspects

Hemoglobins emerging roles in mental disorders. Metabolical, genetical and immunological aspects

Thalassemia in the laboratory: pearls, pitfalls, and promises

Hemoglobin A2 and Heterogeneous Diagnostic Relevance Observed in Eight New Variants of the Delta Globin Gene

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Hemoglobinopathy testing: the significance of accuracy and pitfalls in HbA2 determination

Cited by 6 publications

References 8 publications

Hemoglobins emerging roles in mental disorders. Metabolical, genetical and immunological aspects

Hemoglobins emerging roles in mental disorders. Metabolical, genetical and immunological aspects

Thalassemia in the laboratory: pearls, pitfalls, and promises

Hemoglobin A2 and Heterogeneous Diagnostic Relevance Observed in Eight New Variants of the Delta Globin Gene

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Product

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Hemoglobinopathy testing: the significance of accuracy and pitfalls in HbA₂ determination