Deferiprone vs deferoxamine for transfusional iron overload in SCD and other anemias: a randomized, open-label noninferiority study.

Many people with sickle cell disease (SCD) or other anemias require chronic blood transfusions, which often causes iron overload that requires chelation therapy. The iron chelator deferiprone is frequently used in individuals with thalassemia syndromes, but data in patients with SCD are limited. This open-label study assessed the efficacy and safety of deferiprone in patients with SCD or other anemias receiving chronic transfusion therapy. A total of 228 patients (mean age: 16.9 [range, 3-59] years; 46.9% female) were randomized to receive either oral deferiprone (n = 152) or subcutaneous deferoxamine (n = 76). The primary endpoint was change from baseline at 12 months in liver iron concentration (LIC), assessed by R2* magnetic resonance imaging (MRI). The least squares mean (standard error) change in LIC was -4.04 (0.48) mg/g dry weight for deferiprone vs -4.45 (0.57) mg/g dry weight for deferoxamine, with noninferiority of deferiprone to deferoxamine demonstrated by analysis of covariance (least squares mean difference 0.40 [0.56]; 96.01% confidence interval, -0.76 to 1.57). Noninferiority of deferiprone was also shown for both cardiac T2* MRI and serum ferritin. Rates of overall adverse events (AEs), treatment-related AEs, serious AEs, and AEs leading to withdrawal did not differ significantly between the groups. AEs related to deferiprone treatment included abdominal pain (17.1% of patients), vomiting (14.5%), pyrexia (9.2%), increased alanine transferase (9.2%) and aspartate transferase levels (9.2%), neutropenia (2.6%), and agranulocytosis (0.7%). The efficacy and safety profiles of deferiprone were acceptable and consistent with those seen in patients with transfusion-dependent thalassemia. This trial study was registered at www://clinicaltrials.gov as #NCT02041299.

Cultural preferences and limited public resources influence the spectrum of thalassemia in Egypt.

BACKGROUND: Cultural beliefs of Egyptians with respect to the origin of thalassemia and its prevention, as well as national resources available for care, often differ from those of Western countries. OBJECTIVES: To assess the impact of cultural attitudes and the effect of limited medical and financial resources that could affect the management of Egyptian thalassemic patients. SUBJECTS: A cross sectional study included 205 Egyptians ß-thalassemia major (ß-TM) patients, with a mean age of 149±87.90 months and a male to female ratio of 94:111. METHODS: Demographic data stressing on order of birth, consanguineous marriage, and family history of ß-TM, transfusion, and chelation therapy, were reported. HCV-Ab, HBV-Ag, and complete blood count were recorded with calculation of mean pretransfusional hemoglobin. RESULTS: The age distribution was relatively nonhomogenous, with 39% of patients between 10 and 20 years of age and 16% were younger than 5. There were high family birth rates and 35% of patients were third or more in order of birth and a marked cultural preference for consanguineous marriage, representing 61% of all the parents' marriages, as well as a high rate (59.5%) of a positive family history of ß-TM. Patients transfused on low pretransfusion hemoglobin levels around 8 g/dL, and those receiving blood transfusion before the establishment of National Blood Transfusion Services showed a statistically significant higher rate of positive hepatitis B and C viral infections. Chelation therapy tended to start at late age, mean age was around 4 years. Before 2000, subcutaneous deferoxamine was the most widely used chelation, and since then a considerable number of patients (50%) had started to use oral iron chelators. CONCLUSIONS: The strong cultural preferences for consanguineous marriage and limited preventive programmes and resources have had a negative impact on the management of Egyptians thalassemic patients.

Flow cytometric assessment of circulating platelet and erythrocytes microparticles in young thalassemia major patients: relation to pulmonary hypertension and aortic wall stiffness.

Heart disease is the leading cause of mortality and morbidity in ß-thalassemia major (ß-TM). Aggregability of abnormal red cells and membrane-derived microparticles (MPs) stemming from activated platelets and erythrocytes are responsible for thrombotic risk. We measured platelet and erythrocyte MPs (PMPs and ErMPs) in 60 young ß-TM patients compared with 40 age- and sex-matched healthy controls and assessed their relation to clinicopathological characteristics and aortic elastic properties. Patients were studied stressing on transfusion history, splenectomy, thrombotic events, chelation therapy, hematological and coagulation profiles, flow cytometric measurement of PMPs (CD41b(+) ) and ErMPs (glycophorin A(+) ) as well as echocardiographic assessment of aortic elastic properties. Aortic stiffness index and pulmonary artery pressure were significantly higher, whereas aortic strain and distensibility were lower in TM patients than controls (P < 0.001). Both PMPs and ErMPs were significantly elevated in TM patients compared with controls, particularly patients with risk of pulmonary hypertension, history of thrombosis, splenectomy or serum ferritin >2500 µg/L (P < 0.001). Compliant patients on chelation therapy had lower MPs levels than non-compliant patients (P < 0.001). PMPs and ErMPs were positively correlated to markers of hemolysis, serum ferritin, D-dimer, vWF Ag, and aortic stiffness, whereas negatively correlated to hemoglobin level and aortic distensibility (P < 0.05). We suggest that increased MPs may be implicated in vascular dysfunction, pulmonary hypertension risk, and aortic wall stiffness observed in thalassemia patients. Their quantification could provide utility for early detection of cardiovascular abnormalities and monitoring the biological efficacy of chelation therapy.

Clinicopathological and radiological study of Egyptian ß-thalassemia intermedia and ß-thalassemia major patients: relation to complications and response to therapy.

The clinico epidemiological characteristics, frequency of complications, and response to various therapeutic modalities in 80 Egyptian ß-thalassemia intermedia (ß-TI) patients were compared with 70 ß-thalassemia major (ß-TM) patients. ß-Thalassemia intermedia patients had a higher incidence of left atrium dilatation, right ventricular dilatation and pulmonary hypertension, whereas, ß-TM patients showed a higher incidence of left ventricular (LV) dilatation, restrictive LV filling and impaired LV contractility, with an overall higher incidence of heart disease (p <0.001). Short stature, delayed puberty, osteoporosis, bone fractures, diabetes mellitus and viral hepatitis was frequently observed in ß-TM patients compared with ß-TI patients (p <0.05). Administration of hydroxyurea (HU) alone was associated with significant improvement in hematological parameters and quality of life for ß-TI patients. In conclusion, the risk of complications still burdens the life of Egyptian thalassemia patients and their frequency varies between ß-TI and ß-TM. We provide evidence that calls for the use of HU in ß-TI patients.