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

In transfusion-dependent thalassemia major, iron-induced cardiomyopathy is the predominant cause of morbidity and mortality. Assessment of myocardial iron loading using MRI gradient echo T2* measurements have been described, but has only been performed at one centre in London. We assessed the transferability of this method by comparing the results from three different MR scanners in three different countries. Ten patients with thalassemia major underwent myocardial T2* assessment using a Siemens Sonata Scanner in London. Patients were also scanned with either a similar T2* sequence on a GE Systems CVI scanner in Athens, or a GE Systems signa echospeed scanner in Cagliari. Two scans were performed at the respective site in all patients to assess interstudy reproducibility at each site. The mean difference and coefficient of variability for the heart between scanners was 0.08 ms and 9.7% between London and Athens; and 0.30 ms and 1.6% between London and Cagliari. The interstudy mean difference and coefficient of variability for the heart in Athens was 0.6 ms and 3.5%, and 0.2 ms and 2.4% in Cagliari. In conclusion, the myocardial iron estimations were consistent between the three centres with scanners of differing manufacture, suggesting that this technique may have widespread application in the assessment of patients with iron overload conditions such as thalassaemia.
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PMID:Intercentre reproducibility of magnetic resonance T2* measurements of myocardial iron in thalassaemia. 1617 43

Iron cardiomyopathy remains the leading cause of death in patients with thalassemia major. Magnetic resonance imaging (MRI) is ideally suited for monitoring thalassemia patients because it can detect cardiac and liver iron burdens as well as accurately measure left ventricular dimensions and function. However, patients with thalassemia have unique physiology that alters their normative data. In this article, we review the physiology and pathophysiology of thalassemic heart disease as well as the use of MRI to monitor it. Despite regular transfusions, thalassemia major patients have larger ventricular volumes, higher cardiac outputs, and lower total vascular resistances than published data for healthy control subjects; these hemodynamic findings are consistent with chronic anemia. Cardiac iron overload increases the relative risk of further dilation, arrhythmias, and decreased systolic function. However, many patients are asymptomatic despite heavy cardiac burdens. We explore possible mechanisms behind cardiac iron-function relationships and relate these mechanisms to clinical observations.
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PMID:Physiology and pathophysiology of iron cardiomyopathy in thalassemia. 1633 87

The incidence of cardiomyopathy was monitored in a 6-year follow-up study involving 56 transfused thalassemia patients treated with deferoxamine (DFO), deferiprone (L1) or their combination. During this period, five female patients on regular subcutaneous or intravenous DFO presented with cardiac complications. Three patients suffered congestive heart failure and the other two arrhythmias. Four of the five patients maintained serum ferritin levels of about 1 mg/L or below and the fifth about 1.5 mg/L for several years prior to the cardiomyopathy. Cardiac magnetic resonance imaging (MRI) T2* and T2 was performed in four patients after the cardiomyopathy, identifying the presence of moderate-to-heavy siderosis. The treatment of the five patients has since changed, involving mainly the use of L1. Low serum ferritin levels appear to be misleading for detecting cardiac iron overload and this may increase the risk of cardiomyopathy. The MRI T2 and T2* relaxation time measurements are a more accurate method of detecting cardiac iron overload. Chelation therapy using L1 or appropriate L1/DFO combinations can reduce cardiac iron overload and the mortality rate in thalassemia patients.
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PMID:Low serum ferritin levels are misleading for detecting cardiac iron overload and increase the risk of cardiomyopathy in thalassemia patients. The importance of cardiac iron overload monitoring using magnetic resonance imaging T2 and T2*. 1679 47

Cardiac damage caused by iron overload toxicity is the main cause of death in thalassemia patients. Biopsy samples of poorly chelated thalassemia patients who suffered congestive cardiac failure (CCF) show extensive iron deposition in the myocardium. In one patient who survived CCF, a cardiac biopsy was performed during the removal of a thrombus caused by a port-a-cath, which was used for the administration of intravenous (iv) deferoxamine (DFO). Ultrastructural pathology studies of the cardiac biopsy indicated extensive iron deposition in myocytes with accumulation of iron mainly in lysosomes, leading in some cases to their disruption. Damage to other intracellular components of the myocytes and loss of myofibers was also observed. The patient became intolerant to iv and subcutaneous (sc) DFO 2 years after the CCF, and was then treated with deferiprone (L1) for 7 years. Within 1 year of L1 treatment at 75-80 mg/kg/day, serum ferritin levels were reduced to <0.45 mg/L and she became asymptomatic, needing no further drugs for her cardiomyopathy. Lowering the L1 dose to 50-70 mg/kg/day caused an increase in serum ferritin levels. Maintenance of normal iron stores during the last 3 years as detected by cardiac and liver magnetic resonance imaging (MRI) T2 and T2* and normalization of serum ferritin levels (<0.15 mg/L) was observed following L1 therapy at 80-85 mg/kg/day. Deferiprone (>80 mg/kg/day) appears to be effective in the rapid clearance of cardiac iron, in the reversal of iron overload related cardiomyopathy, in the maintenance of normal iron stores and the overall long-term survival of thalassemia patients.
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PMID:Myocyte damage and loss of myofibers is the potential mechanism of iron overload toxicity in congestive cardiac failure in thalassemia. Complete reversal of the cardiomyopathy and normalization of iron load by deferiprone. 1827 79

As a means to manage cardiac conditions, we determined the effects of high-dose intravenous (IV) deferoxamine in 15 thalassaemia patients with cardiomyopathy and high ferritin and haemoglobin levels. The patients received IV deferoxamine, 130 mg/kg per day over 10-14 hours (maximum 5 g) for 5 consecutive days. All patients underwent a full evaluation before receiving deferoxamine, and 2 days and 1 month after completing the treatment. Visual and auditory examinations were done to detect any side-effects. After treatment, cardiovascular symptoms decreased considerably and systolic function showed significant improvement, but there was no significant effect on diastolic function, electrocardiography and physical findings. There were no significant side-effects reported.
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PMID:High-dose deferoxamine treatment (intravenous) for thalassaemia patients with cardiac complications. 1829 Mar 97

Thalassemia is anemia of variable severity, arising from mutations of genes encoding the hemoglobin alpha and beta chains. Severe thalassemia is associated with iron overload, tissue lesions, and high risk for cardiovascular complications, and iron-mediated cardiomyopathy is the main cause of death in this condition. Thalassemia major (TM) patients exhibit cardiovascular abnormalities consistent with chronic anemia; these include enlargement of the ventricular chambers, increased cardiac output, and reduced total vascular resistance. Cardiac iron overload in TM patients due to long-term transfusion can cause further chamber dilation, decreased contractility, and arrhythmia. Paradoxically, many such patients remain asymptomatic until decompensation occurs. For decades, magnetic resonance imaging and echocardiography have been performed to detect advanced cardiac dysfunction; however, reliable evaluation tools for the early detection of cardiac abnormalities are currently in demand. This article reviews the mechanisms underlying the development of heart disease in thalassemia and strategies for therapeutic intervention in TM patients with congestive heart failure.
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PMID:Mechanisms of and obstacles to iron cardiomyopathy in thalassemia. 1850 36

Data concerning electrocardiographic (ECG) abnormalities in thalassemic cardiomyopathy are scanty. Current techniques to detect early findings of myocardial involvement in thalassemia (Magnetic Resonance, Stress Echo, Tissue Doppler Imaging) are not widely available. We sought to determine whether new ECG abnormalities emerge in thalassemia patients when heart failure due to cardiomyopathy occurs. ECG and Echo Doppler examinations of 28 consecutive adult thalassemia patients with heart failure observed at our hospital were compared with ECG and Echo Doppler examinations performed before the onset of heart dysfunction and with those of 60 age and sex-matched patients with thalassemia without evidence of cardiac involvement. All the patients with heart failure had new ECG abnormalities. New onset supraventricular arrhythmias, T wave inversion, low voltages, right QRS axis deviation and S1Q3 pattern developed respectively in 46%, 79%, 43%, 18% and 15% of thalassemic patients with heart failure. None of the patients without heart failure showed any ECG abnormality (P<0.001). In conclusion this study suggests that new onset ECG abnormalities are always evident in patients with and always absent in patients without heart failure due to thalassemic cardiomyopathy.
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PMID:Electrocardiographic abnormalities in thalassemia patients with heart failure. 1927 75

Free radical formation is primarily initiated from metal catalytic centers involving iron and copper. Under certain conditions, free radical reactions can lead to free radical cascades and oxidative stress, which can cause biomolecular, cellular and tissue damage (FRD). The use of natural antioxidants to prevent FRD is in most cases not effective. Many chelators have been shown to inhibit free radical reactions and toxicity in experimental models of both in vitro and in vivo. Deferiprone (L1) has been shown to be effective and safe in the reversal of accelerating oxidative stress related tissue damage in iron loading and non iron loading conditions such as cardiomyopathy in thalassaemia, acute kidney disease and Friedreich ataxia. The selection of chelating drugs and their combinations could be used as new strategies for antioxidant therapies. In vitro, in vivo and clinical data suggest that L1 is the most potent drug antioxidant because of its high therapeutic index, ability to reach extracellular and intracellular compartments of many tissues and ability to inhibit both iron and copper catalysed free radical reactions.
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PMID:Prospects for introducing deferiprone as potent pharmaceutical antioxidant. 1948 34

Tissue damage caused by oxidative stress is a common characteristic of many conditions involving different major organs such as the brain, heart, liver and kidneys. The treatment of such conditions using classical antioxidants is not in most cases sufficient or effective because it lacks specificity and has a low therapeutic index. Increased evidence from in vitro, in vivo and clinical studies suggest that deferiprone (L1) can be used as a potent pharmaceutical antioxidant by mobilizing labile iron and copper and/or inhibiting their catalytic activity in the formation of free radicals and oxidative stress in tissue damage. The high therapeutic index, tissue penetration, rapid iron binding and clearance of the iron complex, and the low toxicity of L1, support its application as an antioxidant pharmaceutical for adjuvant, alternative or main therapy, especially in conditions where other treatments have failed. Substantial clinical improvement and reversal in most cases of the tissue damage has been observed in cardiomyopathy in thalassemia, diabetic nephropathy and glomerulonephritis in kidney disease, Friedreich's Ataxia and Fanconi Anemia patients. In contrast to L1, both deferoxamine (DFO) and deferasirox (DFRA) have major disadvantages in their use in non iron loading conditions due to toxicity implications. Further studies in the above and other conditions and optimization of the L1 therapy in each individual will increase the prospects of the application and role of L1 as a universal antioxidant pharmaceutical.
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PMID:Risk/benefit assessment, advantages over other drugs and targeting methods in the use of deferiprone as a pharmaceutical antioxidant in iron loading and non iron loading conditions. 1981 84

This review highlights recent advances in iron metabolism that are relevant to sickle cell disease (SCD). SCD is a common hemoglobinopathy that results in chronic inflammation. Improved understanding of how iron metabolism is controlled by proteins such as hepcidin, ferroportin, hypoxia-inducible factor 1, and growth differentiation factor 15 have revealed how they are involved in the organ toxicity of SCD. SCD patients have lower levels of non-transferrin-bound iron (NTBI) relative to other hemoglobinopathies, such as thalassemia. Care for SCD now commonly uses transfusion that results in iron overload and necessitates the need for chelation. New oral chelation therapy using deferasirox (Exjade/ICL670) appears to be safe and may even lower the amount of toxic free NTBI and enhance patient compliance. Finally, we suggest that iron metabolism and trafficking is different in SCD compared to other hemoglobinopathies. The high levels of inflammatory cytokines in SCD may enhance macrophage/reticuloendothelial cell iron and/or renal cell iron retention. This makes the tissues that retain iron different in SCD, and thus the organs that fail in SCD are different from those of other hemoglobinopathies, such as the cardiomyopathy or endocrinopathies of thalassemia.
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PMID:Iron metabolism and iron chelation in sickle cell disease. 1990 55


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