Survival and Complications in Thalassemia

Borgna‐Pignatti, Caterina; Cappellini, Maria Domenica; Stefano, Piero De; Vecchio, Giovanni Carlo Del; Forni, Gian Luca; Gamberini, Maria Rita; Ghilardi, Roberta; Origa, Raffaella; Piga, Antonio; Romeo, Maria Antonietta; Zhao, Huaqing; Cnaan, Avital

doi:10.1196/annals.1345.006

Cited by 364 publications

(288 citation statements)

References 19 publications

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“…NTBI in the circulation damages the heart, endocrine organs, and liver (21). NTBI serves as a catalyst for the formation of ROS, which can cause myocyte damage, arrhythmias, and congestive heart failure, the main causes of death in patients with β-thalassemia (22). Therefore, development of new strategies to reduce excessive iron absorption and tissue iron overload is one of the primary goals of improved management for β-thalassemic patients.…”

Section: Discussionmentioning

confidence: 99%

Hepcidin as a therapeutic tool to limit iron overload and improve anemia in β-thalassemic mice

Gardenghi¹,

Ramos²,

Marongiu³

et al. 2010

J. Clin. Invest.

204

215

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Excessive iron absorption is one of the main features of β-thalassemia and can lead to severe morbidity and mortality. Serial analyses of β-thalassemic mice indicate that while hemoglobin levels decrease over time, the concentration of iron in the liver, spleen, and kidneys markedly increases. Iron overload is associated with low levels of hepcidin, a peptide that regulates iron metabolism by triggering degradation of ferroportin, an iron-transport protein localized on absorptive enterocytes as well as hepatocytes and macrophages. Patients with β-thalassemia also have low hepcidin levels. These observations led us to hypothesize that more iron is absorbed in β-thalassemia than is required for erythropoiesis and that increasing the concentration of hepcidin in the body of such patients might be therapeutic, limiting iron overload. Here we demonstrate that a moderate increase in expression of hepcidin in β-thalassemic mice limits iron overload, decreases formation of insoluble membrane-bound globins and reactive oxygen species, and improves anemia. Mice with increased hepcidin expression also demonstrated an increase in the lifespan of their red cells, reversal of ineffective erythropoiesis and splenomegaly, and an increase in total hemoglobin levels. These data led us to suggest that therapeutics that could increase hepcidin levels or act as hepcidin agonists might help treat the abnormal iron absorption in individuals with β-thalassemia and related disorders.

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Section: Discussionmentioning

confidence: 99%

Hepcidin as a therapeutic tool to limit iron overload and improve anemia in β-thalassemic mice

Gardenghi¹,

Ramos²,

Marongiu³

et al. 2010

J. Clin. Invest.

204

215

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“…Iron accumulation in the body over the time can damage liver, myocardium, spleen, and endocrine organs, inducing heart failure, diabetes, hypothyroidism, hypogonadism, and hepatic disease as cirrhosis or liver cancer [2] and [3]. The major cause of death reported in transfusion iron overload is heart failure [4].…”

Section: Introductionmentioning

confidence: 99%

A new HPLC UV validated method for therapeutic monitoring of deferasirox in thalassaemic patients

Francia

Massano

Piccione

et al. 2012

Journal of Chromatography B

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We describe a new high performance liquid chromatography coupled with ultraviolet detection method for the quantification of plasma concentration of oral iron chelating agent deferasirox. A simple protein precipitation extraction procedure was applied on 500 μl of plasma aliquots. Chromatographic separation was achieved on a C18 reverse phase column and eluate was monitored at 295 nm, with 8 min of analytical run. This method has been validated following Food and Drug Administration procedures: mean intra and inter day variability was 4.64 and 10.55%; mean accuracy was 6.27%; mean extraction recovery 91.66%. Calibration curves ranged from 0.078125 to 40 μg/ml. Limit of quantification was set at 0.15625 while limit of detection at 0.078125 μg/ml. We applied methodology developed on plasma samples of thalassaemic patients treated with deferasirox, finding correlation between deferasirox plasma concentrations and serum ferritin levels. This methodology allowed a specific, sensitive and reliable determination of deferasirox, that could be useful to perform its therapeutic monitoring and pharmacokinetic studies in patients plasma.

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“…3,4 Iron overload resulting in cardiomyopathy is the most common cause of death in patients with transfusion-dependent thalassemia, 5 but those with nontransfusion-dependent thalassemia are also at high risk for iron overload and its complications, especially hepatic and endocrine disease. 6 Patients with severe thalassemia phenotypes require transfusion to suppress erythropoiesis and maintain function, whereas patients with moderate and milder forms can be managed conservatively.…”

Section: Introductionmentioning

confidence: 99%

Hepcidin is suppressed by erythropoiesis in hemoglobin E β-thalassemia and β-thalassemia trait

Jones

Pasricha

Allen

et al. 2015

Blood

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Key Points• Expanded erythropoiesis strongly drives hepcidin suppression in severe transfusion-dependent HbE b-thalassemia.• b-thalassemia carriers, but not HbE carriers, have enhanced erythropoiesis associated with mildly suppressed hepcidin.Hemoglobin E (HbE) b-thalassemia is the most common severe thalassemia syndrome across Asia, and millions of people are carriers. Clinical heterogeneity in HbE b-thalassemia is incompletely explained by genotype, and the interaction of phenotypic variation with hepcidin is unknown. The effect of thalassemia carriage on hepcidin is also unknown, but it could be relevant for iron supplementation programs aimed at combating anemia. In 62 of 69 Sri Lankan patients with HbE b-thalassemia with moderate or severe phenotype, hepcidin was suppressed, and overall hepcidin inversely correlated with iron accumulation. On segregating by phenotype, there were no differences in hepcidin, erythropoiesis, or hemoglobin between severe or moderate disease, but multiple linear regression showed that erythropoiesis inversely correlated with hepcidin only in severe phenotypes. In moderate disease, no independent predictors of hepcidin were identifiable; nevertheless, the low hepcidin levels indicate a significant risk for iron overload. In a population survey of Sri Lankan schoolchildren, b-thalassemia (but not HbE) trait was associated with increased erythropoiesis and mildly suppressed hepcidin, suggesting an enhanced propensity to accumulate iron. In summary, the influence of erythropoiesis on hepcidin suppression associates with phenotypic disease variation and pathogenesis in HbE b-thalassemia and indicates that the epidemiology of b-thalassemia trait requires consideration when planning public health iron interventions. (Blood. 2015;125(5):873-880)

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Survival and Complications in Thalassemia

Cited by 364 publications

References 19 publications

Hepcidin as a therapeutic tool to limit iron overload and improve anemia in β-thalassemic mice

Hepcidin as a therapeutic tool to limit iron overload and improve anemia in β-thalassemic mice

A new HPLC UV validated method for therapeutic monitoring of deferasirox in thalassaemic patients

Hepcidin is suppressed by erythropoiesis in hemoglobin E β-thalassemia and β-thalassemia trait

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