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Query: UMLS:C0039730 (thalassemia)
 10,305 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The life expectancy of patients with thalassemia major has significantly increased in recent years, as reported by several groups in different countries. However, complications are still frequent and affect the patients' quality of life. In a recent study from the United Kingdom, it was found that 50% of the patients had died before age 35. At that age, 65% of the patients from an Italian long-term study were still alive. Heart disease is responsible for more than half of the deaths. The prevalence of complications in Italian patients born after 1970 includes heart failure in 7%, hypogonadism in 55%, hypothyroidism in 11%, and diabetes in 6%. Similar data were reported in patients from the United States. In the Italian study, lower ferritin levels were associated with a lower probability of experiencing heart failure and with prolonged survival. Osteoporosis and osteopenia are common and affect virtually all patients. Hepatitis C virus antibodies are present in 85% of multitransfused Italian patients, 23% of patients in the United Kingdom, 35% in the United States, 34% in France, and 21% in India. Hepatocellular carcinoma can complicate the course of hepatitis. A survey of Italian centers has identified 23 such cases in patients with a thalassemia syndrome. In conclusion, rates of survival and complication-free survival continue to improve, due to better treatment strategies. New complications are appearing in long-term survivors. Iron overload of the heart remains the main cause of morbidity and mortality.
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PMID:Survival and complications in thalassemia. 1633 50

Magnetic resonance T2* values of the myocardium are directly related to tissue iron levels. Minor effects from myocardial oxygenation and fibrosis are overwhelmed by the highly dominant iron effect in clinically relevant levels of myocardial iron overload. Myocardial T2* values less than 20 ms indicate iron overload, and this is considered severe when T2* is less than 10 ms. Decreasing myocardial T2* levels are associated with systolic and diastolic ventricular dysfunction. Most recorded cases of heart failure in thalassemia to date have occurred in patients with very low T2* values (in the severe range). Exceptions to this have occurred in patients with other causes of heart failure such as concomitant congenital heart disease. In patients presenting with heart failure who undergo aggressive chelation with continuous intravenous deferoxamine, longitudinal studies show that myocardial T2* increases, and this is accompanied by increases in ejection fraction and relief of heart failure. In cross-sectional studies, the myocardial T2* and ejection fraction of patients on deferiprone was superior to that of patients on deferoxamine. Randomized controlled prospective trials comparing these two drugs for their action in clearing myocardial iron, as measured by myocardial T2*, are under way and should report in 2005/2006. These trials will clarify the role of different chelators in the management of myocardial iron overload and may be valuable in reducing the toll of death in thalassemia from heart failure.
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PMID:T2* magnetic resonance and myocardial iron in thalassemia. 1633 85

Beta-thalassemia is a hereditary anemia that is quite prevalent in Lebanon. Most patients with beta-Thalassemia are treated and followed up mostly at a multidisciplinary center, located in the suburban area of Beirut: the Chronic Care Center (CCC), operational since 1994. We will review the experience with beta-Thalassemia accumulated through this institution. Four hundred and twenty five patients, aged 2 to 68 years are followed up at the CCC. Sixty four percent have thalassemia major (TM) while 36% have thalassemia intermedia (TI). Lebanese patients with TM receive periodic packed red cell transfusions to maintain a pre-transfusional hemoglobin level of 10 gm/dl at all times and desferrioxamine is the standard iron chelator in use. Since 1994, 12 patients with TM have died from complications of their disease, with heart failure being responsible for the majority of deaths. The incidence of cardiac, endocrinologic, and infectious complications will be reviewed. Finally, both current and prospective preventive measures will be discussed, specifically educational campaigns and premarital screening. The effects of prevention are starting to show as the number of newly diagnosed disease is diminishing.
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PMID:Beta-thalassemia: the Lebanese experience. 1689 58

Despite the introduction of deferoxamine, 50% of thalassaemia major patients die before the age of 35 years predominantly from iron induced heart failure. Indeed, the assessment of myocardial performance may be of particular interest since it can reveal an early myocardial dysfunction. By using impedance cardiography and mass spectrometry, we studied the cardiac function and the oxygen extraction ratio (O(2)ER) of 14 thalassaemic patients and 15 control healthy subjects during an incremental cycle-ergometer test. The achieved mechanical power output and the relative O(2) uptake did not reach any significant difference between groups. At the highest workload, O(2)ER reached significantly higher values in thalassaemic patients versus control subjects while the relationship between cardiac index (CI) and O(2)ER (CI/O(2)ER) decreased showing a lower contribution of cardiovascular system to maintain O(2) uptake. Results of this study imply that CI/O(2)ER allows an early diagnosis of the iron induced myocardial dysfunction, whereas it is not clinically patent yet. To our knowledge, this is the first study revealing an O(2)ER pivotal role as compensatory mechanism to maintain a normal working capacity in subjects suffering from thalassaemia major.
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PMID:Exercise capacity and cardiovascular changes in patients with beta-thalassaemia major. 1704 95

Since the discovery of HFE gene in 1996, considerable progress has been made concerning the iron-metabolism and its major abnormalities. Five types of hereditary hemochromatosis are actually known: type 1 (HFE gene), type 2A (HJV gene), type 2B (HAMP gene), type 3 (TfR2 gene), type 4 (SLC40A1 gene). The HFE C282Y +/+ mutation is responsible for the most frequent type of hemochromatosis in France. Various secondary causes can lead to iron-overload: associated genetic diseases, exogenous iron intake, thalassaemia and refractory anaemia, hepatic siderosis, alcoholic hepatitis, cutaneous porphyria and cirrhosis. The deleterious consequences of iron-overload are due to the interactions of the environmental factors. The role of HFE heterozygote mutations is still discussed. In clinical practice, the interpretation of a serum ferritin increase is a frequent problem that needs a careful evaluation based on the tranferrin saturation measurement. Significant increase of both these factors is in favour of an HFE C282Y +/+ hemochromatosis, after exclusion of a hepatocellular insufficiency or a refractory anaemia. Nevertheless, high ferritin is not always a marker of iron-overload. Thus, there are many disorders increasing the serum ferritin levels without iron overload : cytolysis (hepatic...), inflammatory or infectious syndromes, high alcohol intake, neoplasia... Looking for HFE mutations help to separate type 1 hemochromatosis from other conditions mainly hepatic siderosis (metabolic disorders). The identification of rare types of hemochromatosis (types 2-4) is only required in particular cases. The evaluation of the iron overload is now based on hepatic MRI determination rather than liver biopsy. Repeated phlebotomies remain the essential way to decrease the iron overload in HFE hemochromatosis and to prevent the occurrence of severe and irreversible complications (cirrhosis, arthropathies, cardiac failure, and diabetes). Because of the link established between the amount of iron-overload and the occurrence of complications and the mortality over-risk in HFE C282Y +/+ hemochromatosis, venesections must be started when serum ferritin is higher than 300 microg/l in man and 200 microg/l in woman, whatever the clinical manifestations are and obviously before the symptomatic phase of the disease.
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PMID:[Hereditary and acquired iron overload]. 1737 75

This review outlines the main chelator groups studied to date, and the evidence for their clinical effectiveness. For each treatment, the strength of evidence was documented according to the guidelines from the American College of Cardiology and the American Heart Association. Three main haematological diseases were considered as models: thalassaemia major, sickle-cell disorders and myelodysplasia. Although the data in the literature do not allow firmly evidence-based conclusions, the findings suggest that in thalassaemia major: (i) deferoxamine remains the drug of choice for chelation treatment; (ii) if there is deferoxamine intolerance or a change of treatment is suggested, the options are deferiprone or, if the liver iron concentration is high, deferasirox treatment; and (iii) if the ferritin level is >2500 microg/l and liver iron concentation is >7 mg/g/dry weight, continuous subcutaneous (s.c.) or intravenous (i.v.) deferoxamine, or combined treatment with deferiprone and deferoxamine is advised. In case of heart failure, there is currently more solid documentation to support continuous s.c. or i.v. deferoxamine treatment than combined treatment with deferiprone and deferoxamine. However, more recent data in the literature suggest that the latter could be a satisfactory alternative. Finally, if iron chelation is required for sickle-cell disorders or myelodysplastic syndromes, the current data support the use of deferoxamine treatment.
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PMID:Light and shadows in the iron chelation treatment of haematological diseases. 1765 52

Chronic hypercoagulable state expressed clinically by thromboembolic events has been described in thalassemia. One of the affected organs is the brain where symptomatic and asymptomatic damage has been reported. The present report describes seven cases who presented with the signs of cerebrovascular accident (CVA), five ischemic and two with hemorrhage. Two of them died. All patients were splenectomized, five received regular blood transfusions, and their ferritin levels were between 1,200 and 3,000 mg %. In addition, four patients had congestive heart failure and atrial fibrillation, and three had "Bronze diabetes," The recommendation on the basis of the results is that well-designed clinical trials are indicated to monitor asymptomatic brain damage by magnetic resonance imaging in splenectomized patients over the age of 20 years, who are not regularly transfused and have a high risk to develop thromboembolic events. In this subset of patients, anticoagulant and/or antiplatelet therapy should be considered. Moreover, treatment of additional complications resulting from iron overload, which may contribute to the etiology of CVA such as cardiac failure and arrhythmia with or without "bronze diabetes," is mandatory.
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PMID:Cerebrovascular accident in beta-thalassemia major (beta-TM) and beta-thalassemia intermedia (beta-TI). 1818 11

In thalassemia, deficient globin-chain production during erythropoiesis results in anemia. Thalassemia may be further complicated by iron overload (frequently exacerbated by blood transfusion), which induces numerous endocrine diseases, hepatic cirrhosis, cardiac failure and even death. Accumulation of iron in the absence of blood transfusions may result from inappropriate suppression of the iron-regulating peptide hepcidin by an erythropoietic mechanism. To test this hypothesis, we examined erythroblast transcriptome profiles from 15 healthy, nonthalassemic donors. Growth differentiation factor 15 (GDF15), a member of the transforming growth factor-beta superfamily, showed increased expression and secretion during erythroblast maturation. Healthy volunteers had mean GDF15 serum concentrations of 450 +/- 50 pg/ml. In comparison, individuals with beta-thalassemia syndromes had elevated GDF15 serum levels (mean 66,000 +/- 9,600 pg/ml; range 4,800-248,000 pg/ml; P < 0.05) that were positively correlated with the levels of soluble transferrin receptor, erythropoietin and ferritin. Serum from thalassemia patients suppressed hepcidin mRNA expression in primary human hepatocytes, and depletion of GDF15 reversed hepcidin suppression. These results suggest that GDF15 overexpression arising from an expanded erythroid compartment contributes to iron overload in thalassemia syndromes by inhibiting hepcidin expression.
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PMID:High levels of GDF15 in thalassemia suppress expression of the iron regulatory protein hepcidin. 1782 18

Cardiac events, including heart failure and arrhythmias, are the leading cause of death in patients with beta thalassemia. Although cardiac arrhythmias in humans are believed to result from iron overload, excluding confounding factors in the human population is difficult. The goal of the current study was to determine whether cardiac arrhythmias occurred in the guinea pig model of secondary iron overload. Electrocardiograms were recorded by using surgically implanted telemetry devices in guinea pigs loaded intraperitoneally with iron dextran (test animals) or dextran alone (controls). Loading occurred over approximately 6 wk. Electrocardiograms were recorded for 1 wk prior to loading, throughout loading, and for approximately 4 wk after loading was complete. Cardiac and liver iron concentrations were significantly increased in the iron-loaded animals compared with controls and were in the range of those reported for humans with thalassemia. Arrhythmias were rare in both iron-loaded and control guinea pigs. No life-threatening arrhythmias were detected in either group. These data suggest that iron alone may be insufficient to cause cardiac arrhythmias in the iron-loaded guinea pig model and that arrhythmias detected in human patients with iron overload may be the result of a complex interplay of factors.
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PMID:Iron does not cause arrhythmias in the guinea pig model of transfusional iron overload. 1780 53

Congestive heart failure is the most common cause of death in patients with thalassemia, as chronic accumulation of iron due to regular blood transfusions leads to biventricular systolic dysfunction and death at a very young age. The quantity of iron deposited in the heart is a key determinant of outcome. Early diagnosis and intensive chelation of the cardiac iron can avert heart failure and its fatal outcome.
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PMID:Getting the iron out: preventing and treating heart failure in transfusion-dependent thalassemia. 1802


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