Summary Magnetic resonance imaging (MRI) appears to be useful for monitoring iron overload in thalassaemia. We studied 106 patients with beta‐thalassaemia: 80 with thalassaemia major (TM) and 26 with thalassaemia intermedia (TI). Thirty‐five patients with sickle cell disease (SCD) were also evaluated. Serum ferritin, liver and myocardial T2‐relaxation time and liver iron concentration (LIC) were measured. LIC values, based on biopsies from 29 patients, showed a close inverse correlation with the respective liver T2‐values, along with a strong positive correlation with ferritin levels in all patients. Heart T2‐values correlated with left ventricular ejection fraction in TM and SCD, but not in TI patients. Both liver and heart T2‐values were significantly lower in TM patients than those of TI, and SCD patients. Ferritin levels showed a strong correlation with liver T2‐values in all three groups of patients. Similarly, a negative correlation was found between serum ferritin levels and heart T2‐values in TM, but not in TI and SCD patients. Heart and liver T2‐values showed a significant correlation only in TM patients. These results suggest that the MRI technique (T2 relaxation time) used in our study, is a reliable, safe and non‐invasive method for the assessment of the deposition of iron in the liver; results for the heart become reliable only when there is heavy iron deposition.

BackgroundHepcidin is a 25-aminoacid cysteine-rich iron regulating peptide. Increased hepcidin concentrations lead to iron sequestration in macrophages, contributing to the pathogenesis of anaemia of chronic disease whereas decreased hepcidin is observed in iron deficiency and primary iron overload diseases such as hereditary hemochromatosis. Hepcidin quantification in human blood or urine may provide further insights for the pathogenesis of disorders of iron homeostasis and might prove a valuable tool for clinicians for the differential diagnosis of anaemia. This study describes a specific and non-operator demanding immunoassay for hepcidin quantification in human sera.Methods and FindingsAn ELISA assay was developed for measuring hepcidin serum concentration using a recombinant hepcidin25-His peptide and a polyclonal antibody against this peptide, which was able to identify native hepcidin. The ELISA assay had a detection range of 10–1500 µg/L and a detection limit of 5.4 µg/L. The intra- and interassay coefficients of variance ranged from 8–15% and 5–16%, respectively. Mean linearity and recovery were 101% and 107%, respectively. Mean hepcidin levels were significantly lower in 7 patients with juvenile hemochromatosis (12.8 µg/L) and 10 patients with iron deficiency anemia (15.7 µg/L) and higher in 7 patients with Hodgkin lymphoma (116.7 µg/L) compared to 32 age-matched healthy controls (42.7 µg/L).ConclusionsWe describe a new simple ELISA assay for measuring hepcidin in human serum with sufficient accuracy and reproducibility.

Objective: To examine effects of iron supplementation on vigilance, attention and conceptual learning in preschool children in Greece. Design: Randomized Double-Blind Placebo Controlled trial of iron. Randomization stratified by iron status and day care center (DCC). Setting: Nine public DCCs in Athens, Greece. Subjects: In all, 49 3-4-y olds (21 anemic, 28 good iron status) with birth weight not less than 2500 g, currently healthy; benign past medical history, IQ Z1 s.d. below the age-adjusted mean, serum Pb r200 ppb (none exceeded 50 ppb), and height, weight and head circumference for age Z10th percentile. Anemia defined as: (1) pretreatment Hgb o112 g/l and TS o16% and ferritin o12 mg/L OR (2) Hgb rise of 410 g/l (T2-T0) with iron supplementation. Good iron status was defined as baseline levels of Hgb 4120 g/l and either TS 420% or serum ferritin 412 mg/l. Intervention: The intervention consisted of a 2-month supplementation of 15 mg iron (and MV) vs placebo (MV alone). Results: After iron treatment, the anemic subjects made significantly fewer errors of commission (14% higher specificity, Po0.05), exhibited 8% higher accuracy (Po0.05) and were significantly more efficient (mean difference ¼ 1.09, Po0.05) than those given placebo. These effects of iron were not found among preschoolers with good iron status. No effects of iron treatment were found on the Oddity Learning task. Conclusions: This study demonstrated that iron supplementation of iron-deficient anemic preschoolers results in an improvement in discrimination, specifically selective attention.

Haemoglobin H (Hb H) disease is the severest form of alpha-thalassaemia compatible with post-natal life and occurs when alpha-thalassaemia mutations interact to reduce alpha-globin synthesis to levels approximately equivalent to the output of a single alpha-globin gene. Hb H disease has variable clinical expression, mainly related to underlying genotypes. The spectrum of alpha-thalassaemia determinants in Greece appears greater than in any other population studied and, in 75 Greek Hb H disease patients, we found 12 alpha-thalassaemia mutations interacting to produce 15 Hb H disease genotypes. Evaluation of haematological, biochemical and clinical findings, and correlation with genotypes, defined genetic predictors of disease severity and factors involved in disease progression. In accordance with previous reports, patients with non-deletion alpha-thalassaemia mutations had more severe clinical expression. Additionally, we found that all patients with the most severe phenotypes had alpha-thalassaemic globin variants. Phenotypic severity was not simply related to the degree of alpha-globin deficiency: high Hb H levels were found to exacerbate anaemia by negatively influencing tissue oxygenation, and both Hb H and alpha-thalassaemic haemoglobin variants appear to reduce red cell survival within the bone marrow and circulation. Together with the long-term follow-up in many patients, this report provides comprehensive information for management of Hb H disease and appropriate family counselling.

The clinical effectiveness of Hydroxyurea in thalassemia is still controversial. The present paper puts together the authors' experience in two groups of patients with thalassemia intermedia and sickle cell/beta-thalassemia treated with varying dosages of hydroxyurea over several months. A third group received hydroxyurea along with recombinant human erythropoietin. Our observations are summarized in that treatment with hydroxyrea results in a significant increase of fetal hemoglobin with no change of the total hemoglobin levels. The drug causes also a considerable increase of the erythrocyte volume and hemoglobin content while the MCHC values remain unchanged. As a rule, and without objective criteria so far, patients state feeling better and having more energy. The authors postulate that this feeling may reflect the significant decrease of ineffective erythropoiesis resulting by the replacement of the poorly hemoglobinized, prematurely dying erythroid progenitor and red cell population by another population of cells with higher hemoglobin content and longer survival, the regeneration of which requires less energy and consumption. As expected, patients with sickle cell/beta-thalassemia have also fewer crises and painful episodes. The above findings are in keeping with the few available reports in the literature.