The efficacy of iron chelator regimes in reducing cardiac and hepatic iron in patients with thalassaemia major: a clinical observational study

<p>Abstract</p> <p>Background</p> <p>Available iron chelation regimes in thalassaemia may achieve different changes in cardiac and hepatic iron as assessed by MR. The aim of this study was to assess the efficacy of four available iron chelator regimes in 232 thalassaemia major patients by assessing the rate of change in repeated measurements of cardiac and hepatic MR.</p> <p>Results</p> <p>For the heart, deferiprone and the combination of deferiprone and deferoxamine significantly reduced cardiac iron at all levels of iron loading. As patients were on deferasirox for a shorter time, a second analysis ("Initial interval analysis") assessing the change between the first two recorded MR results for both cardiac and hepatic iron (minimum interval 12 months) was made. Combination therapy achieved the most rapid fall in cardiac iron load at all levels and deferiprone alone was significantly effective with moderate and mild iron load. In the liver, deferasirox effected significant falls in iron load and combination therapy resulted in the most rapid decline.</p> <p>Conclusion</p> <p>With the knowledge of the efficacy of the different available regimes and the specific iron load in the heart and the liver, appropriate tailoring of chelation therapy should allow clearance of iron. Combination therapy is best in reducing both cardiac and hepatic iron, while monotherapy with deferiprone or deferasirox are effective in the heart and liver respectively. The outcomes of this study may be useful to physicians as to the chelation they should prescribe according to the levels of iron load found in the heart and liver by MR.</p

CARDIAC MAGNETIC RESONANCE IN TRANSFUSION DEPENDENT THALASSAEMIA: ASSESSMENT OF IRON LOAD AND RELATION TO LEFT VENTRICULAR EJECTION FRACTION

International audienceCardiac Magnetic Resonance (CMR) has replaced all other surrogate measurements in the determination of transfusional cardiac iron overload in patients with thalassaemia major. We aimed to determine the diagnostic value of CMR T2* with respect to cardiac dysfunction (CD) as determined by CMR-derived left ventricular ejection fraction (LVEF). Cardiac T2* values and LVEF measured by CMR were recorded in 303 patients with thalassaemia major, at the time of their first CMR. T2* was correlated with LVEF (regression coefficient: 0.57, p 8ms and ≤14 ms and reduced to 9.1% in patients with T2* between 14-20 ms. As the probability of CD is progressively, and not suddenly, reduced with increasing values of T2*, CMR has a limited diagnostic value for cardiac dysfunction (ROC Analysis, AUC = 0.68). Patients with cardiac T2* ≤ 8 ms require careful and intensive management. This risk decreases with increasing values of T2* but even in mildly loaded patients the probability of impaired LVEF is not negligible

Age, beta thalassaemia trait, and iron-deficient anaemia significantly affect reticulocyte indices in pre-school children

Reticulocyte indices are easy to obtain, low cost parameters and have gained interest in the field of diagnosing anaemias of childhood. We assessed distribution, age and gender variation, relation to indices of iron metabolism and diagnostic performance of reticulocyte haemoglobin content (CHr), percentage of microcytic reticulocytes (micro_r), percentage of hypochromic reticulocytes (hypo_r), and percentage of reticulocytes with low CHr (low_CHr) in 386 pre-school children classified in four groups: healthy, iron deficiency (ID), iron deficiency anaemia (IDA), and beta-thalassaemia carriers (beta-thal). Age had a positive effect in CHr (Spearman’s rho = 0.21) and a negative effect in hypo_r (Spearman’s rho = -0.2) in healthy children. CHr and low_CHr were related to ferritin in the IDA group (Spearman’s rho 0.55 and -0.53, respectively). In the beta-thal group, HbA(2) is strongly related to all reticulocyte indices. micro_r and CHr performed best in discriminating between IDA and beta-thal heterozygosity (ROC analysis, area under the curve (AUC): 0.76 and 0.74, respectively). CHr achieved the best AUC (0.58) in identifying ID among children without anaemia. Age, IDA and beta-thal significantly affect reticulocyte indices. CHr and micro_r may have a role as screening tools in discriminating between IDA and beta-thal heterozygosity

Serum transferrin receptors: Distribution and diagnostic performance in pre-school children

Soluble transferrin receptors have gained interest in the field of diagnosing anemias. Reference ranges differ according to the method used for the quantification of sTfR. We aim to explore the distributional properties and diagnostic performance of sTfR in pre-school healthy children as well as in children with beta-thalassemia carriers, iron deficiency with normal hematological phenotype (ID) and iron deficiency anemia (IDA). Circulating sTfR as well as biochemical and hematological indices were determined in 521 pre-school children and four groups (normal children, beta-thalassemia traits, ID and IDA) were formed. Diagnostic performance and distribution of sTfR according to age and in relation to several parameters were evaluated in every group. Three hundred eighty one children (261 normal, 60 beta-thalassemia traits, 44 ID and 16 IDA) aged 1-6 years were included. We found that distribution of sTfR differed significantly among the four groups (Kruskal Wallis p&lt;0.001) with children in the normal group exhibiting lower concentrations compared to all other. A negative correlation between sTfR and age occurred in the normal (beta = -0.12, p&lt;0.001) and the ID groups (beta = -0.13, p = 0.035). In the beta-thal and IDA groups sTfR is correlated to HbA(2) (beta = 0.34, p = 0.001) and ferritin (Spearman’s rho = -0.6, p = 0.014) respectively. An area under the curve equal to 0.63 was achieved by sTfR in distinguishing between normal and ID children. Sensitivity and specificity were 70.5% and 50% respectively at a cut-off of 2.5 mg/l. Levels of sTfR are negatively correlated to age in pre-school children while dyserythropoietic procedures like beta-thal, ID, and IDA significantly affect them. These findings indicated that the accuracy of sTfR in diagnosing ID from normal children is limited. Standardization will allow the use of formulas that combine sTfR and ferritin which are of greater diagnostic value than sTfR alone. (C) 2009 Elsevier Inc. All rights reserved