Renal function in β-thalassemia major receiving desferal versus deferasirox

Introduction: Deferasirox is a new oral iron chelating agent which has been administered in β-thalassemia major patients in last few years. There is some reports regarding nephrotoxicity of this agent; however, no comparative study has been conducted yet. Objectives: The aim of this study was to compare the prevalence of kidney dysfunction in β-thalassemia major patients receiving either desferal or deferasirox as iron chelating agents. Patients and Methods: In this cross-sectional study, adult patients with β-thalassemia major who received 25 mg/kg/d of desferal or 25 mg/kg/d of deferasirox were studied. We compared them for serum calcium (Ca), creatinine (Cr) levels and 24 hours urine collection for proportion of Ca and protein. Estimated glomerular filtration rate (eGFR) was calculated by Cockcroft-Gault formula. Results: Twenty-seven patients receiving desferal and 23 patients receiving deferasirox were evaluated. There was no significant difference of calciuria (P = 0.19), glycosuria (P = 0.508), mean 24-hour urine proteinuria (P = 0.44), mean serum Cr (P = 0.47), serum Ca level (P = 0.067) and mean eGFR (P = 0.42) between two groups. Conclusion: There is no significant difference of hypercalciuria, glycosuria, mean eGFR, proteinuria, and also serum Cr between β-thalassemia major patients who received desferal or deferasirox. © 2018 The Author(s)

Hydroxyurea responsiveness in β-thalassemic patients is determined by the stress response adaptation of erythroid progenitors and their differentiation propensity

β-thalassemia is caused by mutations in the β-globin locus resulting in loss of, or reduced, hemoglobin A (adult hemoglobin, HbA, α2β2) production. Hydroxyurea treatment increases fetal γ-globin (fetal hemoglobin, HbF, α2γ2) expression in postnatal life substituting for the missing adult β-globin and is, therefore, an attractive therapeutic approach. Patients treated with hydroxyurea fall into three categories: i) 'responders' who increase hemoglobin to therapeutic levels; (ii) 'moderate-responders' who increase hemoglobin levels but still need transfusions at longer intervals; and (iii) 'non-responders' who do not reach adequate hemoglobin levels and remain transfusion-dependent. The mechanisms underlying these differential responses remain largely unclear. We generated RNA expression profiles from erythroblast progenitors of 8 responder and 8 non-responder β-thalassemia patients. These profiles revealed that hydroxyurea treatment induced differential expression of many genes in cells from non-responders while it h

Bone mineral density in Iranian adolescents and young adults with β-thalassemia major

The authors investigated the prevalence of low bone mass in patients from Tehran, Iran, with β-thalassemia major (n = 203), aged 10-20 years, and the potential risk factors for osteoporosis in this patient population. Prevalence of osteoporosis was 50.7 in lumbar spine, 10.8 in femur, and 7.9 in both regions with no significant difference between the two genders. The following factors were associated with low BMD: height for age and weight for age below 3rd percentile, delayed puberty or hypogonadism, age when Desferal (for iron chelation) was started, duration of Desferal therapy, and serum zinc. Low serum copper and 25(OH)D were not associated with low BMD. Copyright © Informa Healthcare USA, Inc

Pulmonary function test in transfusion-dependent β-thalassemia patients

β-Thalassaemia is the most common hemoglobinopathies in our region with treatment of regular blood transfusion. Iron overload and hemosiderosis can cause organ involvement. Recent studies have focused on pulmonary involvement and pathophysiology of lung damage. The goal of this study was to investigate the pulmonary abnormalities in thalassemic patients in relation with sign and symptoms and iron overload. The authors studied pulmonary function test (PFT) at the Adult Thalassemia Clinic in Tehran. The history of blood transfusion, iron chelation, respiratory problems, and drug usage was taken. Physical examination, PFT, arterial blood gas (ABG), and chest X-ray (CXR) were done. In total, 139 patients were studied. The mean age was 21.1 years and mean duration of transfusion was 18 years. It was found that 133 patients (95.7) did not have respiratory problems and only 6 (4.3) had some respiratory complaints. In CXR, 100 patients (89.3) had normal lung pattern and others (10.7) had variable degrees of abnormal lung pattern. In ABG, mean of Po2 was 73.5 and mean of O2 saturation was 90.6. In PFT, 101 patients (72.7) had restrictive pattern, 35 (25.1) had normal pattern, and 3 (2.2) had combined pattern. According to vital capacity, the patients were placed in five categories: 54 patients (38.8) normal, 37 (26.6) mild, 35 (25.3) moderate, 10 (7.2) severe, and 3 (2.1) extremely severe pulmonary deficit. There was no statistical significance between PFT results with all variables studied, except duration of blood transfusion, which may be considered a indirect effect of iron load (p =.05, r =.361). According to these results, restrictive pattern was the most common finding (72.7) in PFT, while 95.7 of patients had no respiratory complaint, and in the chest X-ray group, 89.3 had normal pattern. The authors conclude that the lung may be considered a site for organ damage, and alteration of pulmonary function may be expected in transfusion-dependent patients in spite of no pulmonary symptoms or normal CXR. In recent years, because of new iron chelating drugs, doctors can expect thalassemic patients to have a long life-time and need to increase their quality of life. One way to do this is to evaluate the respiratory system by PFT to prevent the squeal of pulmonary disease

The Role of Exercise Stress Echocardiography for Determination of Subclinical Cardiac Involvement in β-Thalassemia Major

β-Thalassemia major (β-TM) patients are at increased risk for cardiovascular diseases. Determination of subclinical cardiac involvement is essential for preventive measures. Thus, we aimed to evaluate the role of stress echocardiography for identification of subclinical cardiac dysfunction in β-TM patients. In this prospective study, 45 β-TM patients who were referred for cardiac evaluation, were enrolled. Exclusion criteria included non sinus rhythm and overt cardiac disease. Stress echocardiography levels and cardiac magnetic resonance imaging (MRI) results were obtained from β-TM patients. Patients were divided into two groups of normal vs. iron overload from cardiac T2* greater or less than 20 msec, respectively. Resting and peak exercise right ventricular stroke volume (RVSV) and left ventricular SV (LVSV) were significantly lower in iron overload vs. normal β-TM patients, respectively (p value <0.05). At peak LV global longitudinal strain (GLS) and myocardial performance index (MPI) were significantly decreased and increased compared with resting in iron overload vs. normal β-TM patients, respectively (p value <0.05). There was a significant relationship between inappropriate hemodynamic response to exercise and lower age (p value = 0.032). Resting LVSV and RVSV seemed better prognosticators for iron overload than LV ejection fraction (LVEF). Decreased GLS and increased MPI at peak exercise could also predict the presence of cardiac iron overload. These measurements by stress echocardiography could be evaluated when cardiac T2* could not be determined. © 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group