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)

Serum Vascular Endothelial Growth Factor (VEGF) levels in patients with alpha thalassemia

 Background: Alpha-thalassemia syndrome includes a group of hereditary anemia in which expression of alpha globin chains is decreased or absent. Impaired RBC in patients with thalassemia causes vessel involvement and endothelial cell vessel disturbance. Vascular Endothelial Growth Factor (VEGF) is the most important regulator for endothelial cell proliferation. So, the aim of this study is to compare the serum VEGF levels in patients with alpha thalassemia and normal control group.Materials and Methods: This case-control study was conducted on 17 patients with alpha thalassemia and 40 healthy people. Serum VEGF levels were measured by enzyme-linked immune sorbent assay (ELISA) kit. Then statistical analysis of results were performed using SPSS 16, value of P <0.05 was considered statistically significant.Results: Mean serum VEGF levels in case and control groups were 2294.19±1552.39 and 598.09±988.17pg/ml, respectively. Serum VEGF levels were higher in patients with alpha thalassemia (P <0.01). There was no significant correlation between serum VEGF levels and Hemoglobin. (P= 0.73).Conclusion: Our study revealed that patients with alpha thalassemia have elevated levels of serum VEGF than normal control group. Further studies with larger sample size are recommended to confirm these observations

Diagnostic utility of bleeding assessment tools in congenital fibrinogen deficiencies

Background: The assessment of clinical history is crucial before referring a patient for further laboratory testing. Bleeding assessment tools (BAT) are developed to standardize clinical evaluation. A small number of patients with congenital fibrinogen deficiencies (CFDs) have been evaluated with these tools without definitive results. Aims: We compared the adequacy of the ISTH-BAT and the European network of rare bleeding disorders bleeding score system (EN-RBD-BSS) to identify patients with CFDs. The correlation between the two BATs and fibrinogen levels and patient clinical grade severity was further analyzed. Methods: We included 100 Iranian patients with CFDs. Routine coagulation and fibrinogen-specific tests (fibrinogen antigen [Fg:Ag] and activity [Fg:C]) were performed. The ISTH-BAT and EN-RBD-BSS were used to assess the bleeding score (BS) of all patients. Results: The ISTH-BAT and EN-RBD-BSS median (range) were 4 (0-16) and 2.21 (-1.49 to 6.71), with a statistically significant moderate correlation between the two systems (r = .597, P < .001). In patients with quantitative deficiencies (afibrinogenemia and hypofibrinogenemia), the correlation between Fg:C and the ISTH-BAT was moderately negative (r = -.4, P < .001), while the correlation between Fg:C and the EN-RBD-BSS was weakly negative (r = -.38, P < .001). Overall, 70% and 72% of patients with fibrinogen deficiencies were correctly identified by both the ISTH-BAT and EN-RBD-BSS, respectively. Conclusion: These results suggest that in addition to the ISTH-BAT, the EN-RBD-BSS may also be useful in identifying CFD patients. We found a significant level of sensitivity for detecting fibrinogen deficiency in the two BATs, and bleeding severity classification correctly identified severity grades in almost two-thirds of patients

Elevated factor VIII activity and venous thromboembolism in patients referred to the Iranian Blood Transfusion Organization: A case control study

ObjectiveA high plasma level of factor eight (FVIII) is a risk factor for venous thromboembolism (VTE). Since, there was no report about the association of elevated FVIII and VTE in Iranian population, the incidence of elevated FVIII and its association to VTE was evaluated.Materials and methods152 consecutive idiopathic VTE patients referred to the Iranian Blood Transfusion Organization (IBTO) and 130 healthy matched blood donors were studied. At least one confirmed idiopathic deep vein thrombosis (DVT) or pulmonary embolism (PE) was found among all cases. The blood samples were collected at least 3 months after DVT/PE diagnosis. The normal reference range was determined by using the Control samples of the donors. FVIII levels were measured using PTT based one-staged assay.ResultsThe FVIII levels in the cases and controls were 157.3±53.4 and 111.8±29.7, respectively. In cases, the lowest and the highest levels of FVIII were 66IU/dl and 364IU/dl, while they were 42IU/dl and 195IU/dl for the controls.There was no relation between gender, age and FVIII level in either group. The normal reference range for the controls was 52–171IU/dl. Considering the cut-off point as 180IU/dl, the elevated values were seen in 28.9% of the case group vs. 3.1% of the control group.ConclusionElevated factor VIII is likely to be a risk factor for VTE. Moreover, a new normal reference range for the Iranian population was defined

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

PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR-γ Pro12Ala POLYMORPHISM AND RISK OF OSTEOPENIA IN β-THALASSEMIA MAJOR PATIENTS

Genetic factors have an important role in the incidence of osteopenia in thalassemia patients. The purpose of this study was to investigate the effect of the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor-γ (PPARγ) gene on bone mineral density (BMD) and subsequently, the rate of osteopenia in β-thalassemia major (β-TM) patients. Blood samples were obtained from 156 β-TM patients referred to the Tehran and Qazvin Thalassemia Clinics. Samples were analyzed for polymorphisms of the PPARγ gene using polymerase chain reaction-restriction fragment length polymorphism (RFLP)-based methods. Multivariate analysis was used to investigate the relationship between the risk of osteopenia and the PPARγ gene polymorphism. Correlation analysis showed that there was a significant association between homozygous wild-type genotypes with susceptibility to osteopenia in β-TM patients (p ¼ 0.024). Logistic regression analysis showed that the risk of osteopenia was significantly (p <0.05) higher in the homozygous wild-type genotype than carriers of the rare alleles. Furthermore, the associations were strengthened in men with a homozygous wild-type genotype after adjustment for age and body mass index (BMI) (p <0.05). This study suggests that the Pro12Ala polymorphism of the PPARγ gene might be an independent factor in BMD level and osteopenia in thalassemia patients