Influence of iron chelators on myocardial iron and cardiac function in transfusion‐dependent thalassaemia: a systematic review and meta‐analysis

Mamtani, Manju; Kulkarni, Hemant

doi:10.1111/j.1365-2141.2008.07122.x

Cited by 34 publications

(26 citation statements)

References 48 publications

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“…The role of CP20 as a shuttle acting independently of transferrin was confirmed by its transfer capacity of iron from ironloaded macrophages to pre-erythroid cells. The potential role of CP20 as a siderophore appears in contradiction with its reported applications for reducing myocardial iron burden and for normalizing cardiac function of thalassemia patients (Mamtani and Kulkarni 2008).…”

Section: Effect Of Iron Chelators On Iron Metabolismmentioning

confidence: 98%

Effects of deferasirox and deferiprone on cellular iron load in the human hepatoma cell line HepaRG

et al. 2009

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Two oral chelators, CP20 (deferiprone) and ICL670 (deferasirox), have been synthesized for the purpose of treating iron overload diseases, especially thalassemias. Given their antiproliferative effects resulting from the essential role played by iron in cell processes, such compounds might also be useful as anticancer agents. In the present study, we tested the impact of these two iron chelators on iron metabolism, in the HepaRG cell line which allowed us to study proliferating and differentiated hepatocytes. ICL670 uptake was greater than the CP20 uptake. The iron depletion induced by ICL670 in differentiated cells increased soluble transferrin receptor expression, decreased intracellular ferritin expression, inhibited (55)Fe (III) uptake, and reduced the hepatocyte concentration of the labile iron pool. In contrast, CP20 induced an unexpected slight increase in intracellular ferritin, which was amplified by iron-treated chelator exposure. CP20 also promoted Fe(III) uptake in differentiated HepaRG cells, thus leading to an increase of both the labile pool and storage forms of iron evaluated by calcein fluorescence and Perls staining, respectively. In acellular conditions, compared to CP20, iron removing ability from the calcein-Fe(III) complex was 40 times higher for ICL670. On the whole, biological responses of HepaRG cells to ICL670 treatment were characteristic of expected iron depletion. In contrast, the effects of CP20 suggest the potential involvement of this compound in the iron uptake from the external medium into the hepatocytes from the HepaRG cell line, therefore acting like a siderophore in this cell model.

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Section: Effect Of Iron Chelators On Iron Metabolismmentioning

confidence: 98%

Effects of deferasirox and deferiprone on cellular iron load in the human hepatoma cell line HepaRG

et al. 2009

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“…Concomitantly, cardiac function tests have to be monitored in an intensive care setting in collaboration with a cardiologist until significant improvement is achieved. [72][73][74] If cardiac studies are abnormal but the patient is clinically well, we recommend maximizing the current chelation regimen.…”

Section: Iron Chelation Therapymentioning

confidence: 99%

How I treat thalassemia

Rachmilewitz

Giardina

2011

Blood

353

285

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The purpose of this article is to set forth our approach to diagnosing and managing the thalassemias, including ␤-thalassemia intermedia and ␤-thalassemia major. The article begins by briefly describing recent advances in our understanding of the pathophysiology of thalassemia. In the discussion on diagnosing the condition, we cover the development of improved diagnostic tools, including the use of very small fetal DNA samples to detect single point mutations with great reliability for prenatal diagnosis of homozygous thalassemia. In our description of treatment strategies, we focus on how we deal with clinical manifestations and longterm complications using the most effective current treatment methods for ␤-thalassemia. The discussion of disease management focuses on our use of transfusion therapy and the newly developed oral iron chelators, deferiprone and deferasirox. We also deal with splenectomy and how we manage endocrinopathies and cardiac complications. In addition, we describe our use of hematopoietic stem cell transplantation, which has produced cure rates as high as 97%, and the use of cord blood transplantation. Finally, we briefly touch on therapies that might be effective in the near future, including new fetal hemoglobin inducers and gene therapy. (Blood. 2011;118(13):3479-3488)

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“…A primary premise of this review document is that cardiac disease is easier and safer to treat at an early stage rather than a late stage when the hazard of death is high. We build on previous, more focused summary reviews and consensus statements on the heart in TM [15][16][17][18][19][20] and build a consensus of the assessment of cardiac function and treatment of HF in TM.…”

Section: Need For Consensus Documentmentioning

confidence: 99%

Cardiovascular Function and Treatment in β-Thalassemia Major

Pennell¹,

Udelson²,

Arai³

et al. 2013

Circulation

332

172

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This aim of this statement is to report an expert consensus on the diagnosis and treatment of cardiac dysfunction in β-thalassemia major (TM). This consensus statement does not cover other hemoglobinopathies, including thalassemia intermedia and sickle cell anemia, in which a different spectrum of cardiovascular complications is typical. There are considerable uncertainties in this field, with a few randomized controlled trials relating to treatment of chronic myocardial siderosis but none relating to treatment of acute heart failure. The principles of diagnosis and treatment of cardiac iron loading in TM are directly relevant to other iron-overload conditions, including in particular Diamond-Blackfan anemia, sideroblastic anemia, and hereditary hemochromatosis. Heart failure is the most common cause of death in TM and primarily results from cardiac iron accumulation. The diagnosis of ventricular dysfunction in TM patients differs from that in nonanemic patients because of the cardiovascular adaptation to chronic anemia in non–cardiac-loaded TM patients, which includes resting tachycardia, low blood pressure, enlarged end-diastolic volume, high ejection fraction, and high cardiac output. Chronic anemia also leads to background symptomatology such as dyspnea, which can mask the clinical diagnosis of cardiac dysfunction. Central to early identification of cardiac iron overload in TM is the estimation of cardiac iron by cardiac T2* magnetic resonance. Cardiac T2* <10 ms is the most important predictor of development of heart failure. Serum ferritin and liver iron concentration are not adequate surrogates for cardiac iron measurement. Assessment of cardiac function by noninvasive techniques can also be valuable clinically, but serial measurements to establish trends are usually required because interpretation of single absolute values is complicated by the abnormal cardiovascular hemodynamics in TM and measurement imprecision. Acute decompensated heart failure is a medical emergency and requires urgent consultation with a center with expertise in its management. The first principle of management of acute heart failure is control of cardiac toxicity related to free iron by urgent commencement of a continuous, uninterrupted infusion of high-dose intravenous deferoxamine, augmented by oral deferiprone. Considerable care is required to not exacerbate cardiovascular problems from overuse of diuretics or inotropes because of the unusual loading conditions in TM. The current knowledge on the efficacy of removal of cardiac iron by the 3 commercially available iron chelators is summarized for cardiac iron overload without overt cardiac dysfunction. Evidence from well-conducted randomized controlled trials shows superior efficacy of deferiprone versus deferoxamine, the superiority of combined deferiprone with deferoxamine versus deferoxamine alone, and the equivalence of deferasirox versus deferoxamine.

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Influence of iron chelators on myocardial iron and cardiac function in transfusion‐dependent thalassaemia: a systematic review and meta‐analysis

Cited by 34 publications

References 48 publications

Effects of deferasirox and deferiprone on cellular iron load in the human hepatoma cell line HepaRG

Effects of deferasirox and deferiprone on cellular iron load in the human hepatoma cell line HepaRG

How I treat thalassemia

Cardiovascular Function and Treatment in β-Thalassemia Major

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