Estimates of the effect on hepatic iron of oral deferiprone compared with subcutaneous desferrioxamine for treatment of iron overload in thalassemia major: a systematic review

BACKGROUND: Beta thalassemia major requires regular blood transfusions and iron chelation to alleviate the harmful accumulation of iron. Evidence on the efficacy and safety of the available agents, desferrioxamine and deferiprone, is derived from small, non-comparative, heterogeneous observational studies. This evidence was reviewed to quantitatively compare the ability of these chelators to reduce hepatic iron. METHODS: The literature was searched using Medline and all reports addressing the effect of either chelator on hepatic iron were considered. Data were abstracted independently by two investigators. Analyses were performed using reported individual patient data. Hepatic iron concentrations at study end and changes over time were compared using ANCOVA, controlling for initial iron load. Differences in the proportions of patients improving were tested using χ(2). RESULTS: Eight of 11 reports identified provided patient-level data relating to 30 desferrioxamine- and 68 deferiprone-treated patients. Desferrioxamine was more likely than optimal dose deferiprone to decrease hepatic iron over the average follow-up of 45 months (odds ratio, 19.0, 95% CI, 2.4 to 151.4). The degree of improvement was also larger with desferrioxamine. CONCLUSIONS: This analysis suggests that desferrioxamine is more effective than deferiprone in lowering hepatic iron. This comparative analysis – despite its limitations – should prove beneficial to physicians faced with the challenge of selecting the optimal treatment for their patients

An international survey of patients with thalassemia major and their views about sustaining life-long desferrioxamine use

BACKGROUND: Management of thalassemia major requires patients to have life-long access to a treatment regimen of regular blood transfusions coupled with iron chelation therapy. The objective of this study was to investigate patients' reasons for missing iron chelation therapy with desferrioxamine, and the support to sustain life-long adherence to treatment. METHODS: From October 1999 to May 2000 a survey of patients with thalassemia major was conducted in ten countries: Cyprus, Egypt, Greece, Hong Kong, India, Iran, Italy, Jordan, Taiwan, and the United States. RESULTS: 1,888 questionnaires (65%) were returned. Most patients (1,573) used desferrioxamine, and 79% administered a dose at least 4 days a week. Inaccessibility of the drug was a common reason for missing a dose in India (51%), and in Iran (25%), whereas, in any other country, it was a reason for less than 17% of patients. Overall, 58% reported reasons for missing a dose related to their beliefs or feelings about the medication, and 42% drug-related side effects. CONCLUSION: Many patients miss doses of desferrioxamine and an opportunity remains to develop interventions that provide more support to sustain use of desferrioxamine

Body iron metabolism and pathophysiology of iron overload

Iron is an essential metal for the body, while excess iron accumulation causes organ dysfunction through the production of reactive oxygen species. There is a sophisticated balance of body iron metabolism of storage and transport, which is regulated by several factors including the newly identified peptide hepcidin. As there is no passive excretory mechanism of iron, iron is easily accumulated when exogenous iron is loaded by hereditary factors, repeated transfusions, and other diseased conditions. The free irons, non-transferrin-bound iron, and labile plasma iron in the circulation, and the labile iron pool within the cells, are responsible for iron toxicity. The characteristic features of advanced iron overload are failure of vital organs such as liver and heart in addition to endocrine dysfunctions. For the estimation of body iron, there are direct and indirect methods available. Serum ferritin is the most convenient and widely available modality, even though its specificity is sometimes problematic. Recently, new physical detection methods using magnetic resonance imaging and superconducting quantum interference devices have become available to estimate iron concentration in liver and myocardium. The widely used application of iron chelators with high compliance will resolve the problems of organ dysfunction by excess iron and improve patient outcomes

How early can myocardial iron overload occur in Beta thalassemia major?

BACKGROUND: Myocardial siderosis is the most common cause of death in patients with beta thalassemia major(TM). This study aimed at investigating the occurrence, prevalence and severity of cardiac iron overload in a young Chinese population with beta TM. METHODS AND RESULTS: We analyzed T2* cardiac magnetic resonance (CMR), left ventricular ejection fraction (LVEF) and serum ferritin (SF) in 201 beta TM patients. The median age was 9 years old. Patients received an average of 13 units of blood per year. The median SF level was 4536 ng/ml and 165 patients (82.1%) had SF>2500 ng/ml. Myocardial iron overload was detected in 68 patients (33.8%) and severe myocardial iron overload was detected in 26 patients (12.6%). Twenty-two patients ≤10 years old had myocardial iron overload, three of whom were only 6 years old. No myocardial iron overload was detected under the age of 6 years. Median LVEF was 64% (measured by CMR in 175 patients). Five of 6 patients with a LVEF<56% and 8 of 10 patients with cardiac disease had myocardial iron overload. CONCLUSIONS: The TM patients under follow-up at this regional centre in China patients are younger than other reported cohorts, more poorly-chelated, and have a high burden of iron overload. Myocardial siderosis occurred in patients younger than previously reported, and was strongly associated with impaired LVEF and cardiac disease. For such poorly-chelated TM patients, our data shows that the first assessment of cardiac T2* should be performed as early as 6 years old

Thalassemias in South Asia:clinical lessons learnt from Bangladesh

Abstract Thalassemias are emerging as a global public health concern. Due to remarkable success in the reduction of childhood mortality by controlling infectious diseases in developing countries, thalassemias are likely to be a major public health concern in the coming decades in South Asia. Despite the fact that Bangladesh lies in the world’s thalassemia belt, the information on different aspects (epidemiology, clinical course, mortality, complications and treatment outcomes) of thalassemias is lacking. In this comprehensive review, the aim is to to depict the epidemiological aspects of thalassemias, mutation profile and current treatment and management practices in the country by sharing the experience of dealing with 1178 cases over 2009–2014 time periods in a specialized thalassemia treatment centre. We have also discussed the preventative strategies of thalassemias from the context of Bangladesh which could be effective for other developing countries

Serum ferritin levels, socio-demographic factors and desferrioxamine therapy in multi-transfused thalassemia major patients at a government tertiary care hospital of Karachi, Pakistan

<p>Abstract</p> <p>Background</p> <p>Beta thalassemia is the most frequent genetic disorder of haemoglobin synthesis in Pakistan. Recurrent transfusions lead to iron-overload manifested by increased serum Ferritin levels, for which chelation therapy is required.</p> <p>Findings</p> <p>The study was conducted in the Pediatric Emergency unit of Civil Hospital Karachi after ethical approval by the Institutional Review Board of Dow University of Health Sciences. Seventy nine cases of beta thalassemia major were included after a written consent. The care takers were interviewed for the socio-demographic variables and the use of Desferrioxamine therapy, after which a blood sample was drawn to assess the serum Ferritin level. SPSS 15.0 was employed for data entry and analysis.</p> <p>Of the seventy-nine patients included in the study, 46 (58.2%) were males while 33 (41.8%) were females. The mean age was 10.8 (± 4.5) years with the dominant age group (46.2%) being 10 to 14 years. In 62 (78.8%) cases, the care taker education was below the tenth grade. The mean serum Ferritin level in our study were 4236.5 ng/ml and showed a directly proportional relationship with age. Desferrioxamine was used by patients in 46 (58.2%) cases with monthly house hold income significant factor to the use of therapy.</p> <p>Conclusions</p> <p>The mean serum Ferritin levels are approximately ten times higher than the normal recommended levels for normal individuals, with two-fifths of the patients not receiving iron chelation therapy at all. Use of iron chelation therapy and titrating the dose according to the need can significantly lower the iron load reducing the risk of iron-overload related complications leading to a better quality of life and improving survival in Pakistani beta thalassemia major patients.</p> <p>Conflicts of Interest: None</p

Factors affecting health-related quality of life in Thai children with thalassemia

<p>Abstract</p> <p>Background</p> <p>Knowledge of the factors associated with health-related quality of life (HRQOL) among patients with thalassemia is essential in developing more suitable clinical, counseling, and social support programs to improve treatment outcomes of these patients. In light of the limited research in this area, this study aims to examine factors associated with HRQOL among children and adolescents with thalassemia in Thailand.</p> <p>Methods</p> <p>A cross-sectional survey was conducted in three selected hospitals in Thailand during June to November 2006. PedsQL™ 4.0 Generic Core Scale (Thai version) was used to assess HRQOL in 315 thalassemia patients between 5 and 18 years of age. Other related clinical characteristics of the patients were collected via medical record review.</p> <p>Results</p> <p>The mean (SD) of the total summary score was 76.67 (11.40), while the means (SD) for the Physical Health Summary score and Psychosocial Health Summary score were 78.24 (14.77) and 75.54 (12.76), respectively. The school functioning subscale scored the lowest, with a mean of 67.89 (SD = 15.92). The following factors significantly affected the HRQOL of the patients: age; age at onset of anemia and age at first transfusion; pre-transfusion hemoglobin (Hb) level; receiving a blood transfusion during the previous three months; and disease severity. In addition, iron chelation therapy had a significant negative effect on HRQOL in the school functioning subscale. In contrast, serum ferritin level, frequency of blood transfusions per year, and gender were not significantly related to HRQOL among these patients. The results from multivariate analysis also confirmed these findings.</p> <p>Conclusions</p> <p>To improve HRQOL of thalassemia patients, suitable programs aimed at providing psychosocial support and a link between the patient, school officials, the family and the physician are important, especially in terms of improving the school functioning score. The findings also confirmed the importance of maintaining a pre-transfusion Hb level of at least 9-10.5 g/dL. In addition, special care and attention should be given to patients with a severe condition, and those who are receiving subcutaneous iron chelation therapy.</p