Haemoglobin E β thalassaemia in Sri Lanka

Premawardhena, Anuja; Fisher, Christopher A.; Olivieri, Nancy F.; Silva, S de; Arambepola, M.; Perera, W; O’Donnell, A.; Peto, Tim E. A.; Viprakasit, Vip; Merson, Laura; Muraca, Giulia M.; Weatherall, D. J.

doi:10.1016/s0140-6736(05)67396-5

Cited by 97 publications

(118 citation statements)

References 5 publications

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“…The detection of HbE is essential for the diagnosis. In simple HbE trait, the HbE levels are 25-30% of the total Hb; the values of HbE vary when co-inherited with a-or b-traits [23,24] ( Table 1).…”

Section: Hbe Carriermentioning

confidence: 99%

Laboratory diagnosis of thalassemia

Brancaleoni

Pierro

Motta

et al. 2016

Int J Lab Hematology

168

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Summary The thalassemias can be defined as α‐ or β‐thalassemias depending on the defective globin chain and on the underlying molecular defects. The recognition of carriers is possible by hematological tests. Both α‐ and β‐thalassemia carriers (heterozygotes) present with microcytic hypochromic parameters with or without mild anemia. Red cell indices and morphology followed by separation and measurement of Hb fractions are the basis for identification of carriers. In addition, iron status should be ascertained by ferritin or zinc protoporphyrin measurements and the iron/total iron‐binding capacity/saturation index. Mean corpuscular volume and mean corpuscular hemoglobin are markedly reduced (mean corpuscular volume: 60–70 fl; MCH: 19–23 pg) in β‐thalassemia carriers, whereas a slight to relevant reduction is usually observed in α‐carriers. HbA2 determination is the most decisive test for β‐carrier detection although it can be disturbed by the presence of δ‐thalassemia defects. In α‐thalassemia, HbA2 can be lower than normal and it assumes significant value when iron deficiency is excluded. Several algorithms have been introduced to discriminate from thalassemia carriers and subjects with iron‐deficient anemia; because the only discriminating parameter is the red cell counts, these formulas must be used consciously. Molecular analysis is not required to confirm the diagnosis of β‐carrier, but it is necessary to confirm the α‐thalassemia carrier status. The molecular diagnosis is essential to predict severe transfusion‐dependent and intermediate‐to‐mild non‐transfusion‐dependent cases. DNA analysis on chorionic villi is the approach for prenatal diagnosis and the methods are the same used for mutations detection, according to the laboratory facilities and expertise.

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Section: Hbe Carriermentioning

confidence: 99%

Laboratory diagnosis of thalassemia

Brancaleoni

Pierro

Motta

et al. 2016

Int J Lab Hematology

168

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“…3,4 Iron overload resulting in cardiomyopathy is the most common cause of death in patients with transfusion-dependent thalassemia, 5 but those with nontransfusion-dependent thalassemia are also at high risk for iron overload and its complications, especially hepatic and endocrine disease. 6 Patients with severe thalassemia phenotypes require transfusion to suppress erythropoiesis and maintain function, whereas patients with moderate and milder forms can be managed conservatively.…”

Section: Introductionmentioning

confidence: 99%

“…First, in 69 patients with HbE b-thalassemia with diverse, well-characterized clinical phenotypes managed at a specialist clinic, 4 we investigated associations between serum hepcidin and parameters of erythropoiesis, iron loading, and inflammation. Second, using samples from a national population-based hemoglobinopathy screening study, we compared erythropoiesis and hepcidin regulation between iron-replete adolescents who carry b-thalassemia or HbE mutations and those without these conditions.…”

Section: Introductionmentioning

confidence: 99%

Hepcidin is suppressed by erythropoiesis in hemoglobin E β-thalassemia and β-thalassemia trait

Jones

Pasricha

Allen

et al. 2015

Blood

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Key Points• Expanded erythropoiesis strongly drives hepcidin suppression in severe transfusion-dependent HbE b-thalassemia.• b-thalassemia carriers, but not HbE carriers, have enhanced erythropoiesis associated with mildly suppressed hepcidin.Hemoglobin E (HbE) b-thalassemia is the most common severe thalassemia syndrome across Asia, and millions of people are carriers. Clinical heterogeneity in HbE b-thalassemia is incompletely explained by genotype, and the interaction of phenotypic variation with hepcidin is unknown. The effect of thalassemia carriage on hepcidin is also unknown, but it could be relevant for iron supplementation programs aimed at combating anemia. In 62 of 69 Sri Lankan patients with HbE b-thalassemia with moderate or severe phenotype, hepcidin was suppressed, and overall hepcidin inversely correlated with iron accumulation. On segregating by phenotype, there were no differences in hepcidin, erythropoiesis, or hemoglobin between severe or moderate disease, but multiple linear regression showed that erythropoiesis inversely correlated with hepcidin only in severe phenotypes. In moderate disease, no independent predictors of hepcidin were identifiable; nevertheless, the low hepcidin levels indicate a significant risk for iron overload. In a population survey of Sri Lankan schoolchildren, b-thalassemia (but not HbE) trait was associated with increased erythropoiesis and mildly suppressed hepcidin, suggesting an enhanced propensity to accumulate iron. In summary, the influence of erythropoiesis on hepcidin suppression associates with phenotypic disease variation and pathogenesis in HbE b-thalassemia and indicates that the epidemiology of b-thalassemia trait requires consideration when planning public health iron interventions. (Blood. 2015;125(5):873-880)

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“…High levels of erythropoietin in thalassemia cause expansion of the erythroid mass with resultant hepatosplenomegaly and bone deformity. In Sri Lankan patients it was found that serum erythropoietin concentrations correlated with steady state hemoglobin concentration, while a significant decline in serum erythropoietin in the face of anemia was observed with advancing age [7] . Other environmental factors such as high frequency of malaria (Plasmodium vivax) could contribute to the clinical phenotype.…”

Section: Introductionmentioning

confidence: 99%

“…Thai investigators have suggested that patients who have co-inherited severe β + or β0 alleles might be more severely affected than those who co-inherited a mild β-thalassemia allele [6] . Studies from India and Srilanka have however, suggested a limited role for β-thalassemia mutation on the clinical severity [4,7] . Co-inheritance of α-thalassemia is a major genetic factor affecting clinical phenotype and considerable number of patients who have a co-existent α-thalassemia may be diagnosed later in life [8] .…”

Section: Introductionmentioning

confidence: 99%