Efficacy, Compliance And Toxicity Factors Are Affecting The Rate Of Normalization Of Body Iron Stores In Thalassemia Patients Using The Deferiprone And Deferoxamine Combination Therapy

Kolnagou, Annita; Kleanthous, Marios; Kontoghiorghes, George J.

doi:10.3109/03630269.2011.576153

Cited by 30 publications

(37 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our present findings confirm previous observations [11,12,13] and validate our hypothesis, as satisfactory ferritin levels were achieved in our study population, which were markedly lower than those reported in earlier studies [2,3]. The results of univariate and discriminant analyses reinforce these considerations.…”

Section: Discussionsupporting

confidence: 82%

“…This view was based on accumulated evidence, indicating that current chelation therapy is effective [11] and is associated with high patient compliance rates [12,13]. A previous study from our Institution demonstrated that combined chelation therapy with deferoxamine and deferiprone results in a satisfactory reduction of serum ferritin without significant toxicity [9].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Determinants of Pulmonary Hypertension in Patients with Beta-Thalassemia Major and Normal Ventricular Function

Vlahos¹,

Koutsouka²,

Papamichael³

et al. 2012

Acta Haematol

View full text Add to dashboard Cite

Background/Aims: We sought to define the incidence and predictive factors of pulmonary hypertension in β-thalassemia major. Methods: We studied 27 consecutive patients (19 male, 38 ± 9 years of age) with β-thalassemia major. All the patients had normal (left and right) ventricular (systolic and diastolic) function and underwent echocardiographic assessment of pulmonary artery systolic pressure. Univariate regression and discriminant function analyses were used to identify predictive factors of pulmonary hypertension. Results: Pulmonary hypertension was observed in 18.5% of the patients, but clinically significant disease was detected in only 3.7%. A total of 14 (51.8%) patients had been receiving a combined administration of deferoxamine and deferiprone for 7.0 ± 1.3 years. Amidst a large number of variables examined, ferritin levels and delayed onset of chelation therapy were the only predictors of pulmonary hypertension. Conclusion: Pulmonary hypertension in β-thalassemia major is relatively infrequent and generally mild due to improved chelation therapy. The role of hemochromatosis in pulmonary hypertension development merits further study.

show abstract

Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Determinants of Pulmonary Hypertension in Patients with Beta-Thalassemia Major and Normal Ventricular Function

Vlahos¹,

Koutsouka²,

Papamichael³

et al. 2012

Acta Haematol

View full text Add to dashboard Cite

show abstract

“…Such protection effect was presented in our in vitro study by deferiprone, the effective iron chelator commonly used in current clinical practice [51]. However, in our assessment, none of the calcium channel blockers showed significant protection effect on iron overload induced apoptosis, though LTCC blockers, in particular amlodipine, presented slight protection at 600 µM of ferric or ferrous iron challenge.…”

Section: Discussionsupporting

confidence: 58%

Iron Overload and Apoptosis of HL-1 Cardiomyocytes: Effects of Calcium Channel Blockade

et al. 2014

View full text Add to dashboard Cite

BackgroundIron overload cardiomyopathy that prevails in some forms of hemosiderosis is caused by excessive deposition of iron into the heart tissue and ensuing damage caused by a raise in labile cell iron. The underlying mechanisms of iron uptake into cardiomyocytes in iron overload condition are still under investigation. Both L-type calcium channels (LTCC) and T-type calcium channels (TTCC) have been proposed to be the main portals of non-transferrinic iron into heart cells, but controversies remain. Here, we investigated the roles of LTCC and TTCC as mediators of cardiac iron overload and cellular damage by using specific Calcium channel blockers as potential suppressors of labile Fe(II) and Fe(III) ingress in cultured cardiomyocytes and ensuing apoptosis.MethodsFe(II) and Fe(III) uptake was assessed by exposing HL-1 cardiomyocytes to iron sources and quantitative real-time fluorescence imaging of cytosolic labile iron with the fluorescent iron sensor calcein while iron-induced apoptosis was quantitatively measured by flow cytometry analysis with Annexin V. The role of calcium channels as routes of iron uptake was assessed by cell pretreatment with specific blockers of LTCC and TTCC.ResultsIron entered HL-1 cardiomyocytes in a time- and dose-dependent manner and induced cardiac apoptosis via mitochondria-mediated caspase-3 dependent pathways. Blockade of LTCC but not of TTCC demonstrably inhibited the uptake of ferric but not of ferrous iron. However, neither channel blocker conferred cardiomyocytes with protection from iron-induced apoptosis.ConclusionOur study implicates LTCC as major mediators of Fe(III) uptake into cardiomyocytes exposed to ferric salts but not necessarily as contributors to ensuing apoptosis. Thus, to the extent that apoptosis can be considered a biological indicator of damage, the etiopathology of cardiosiderotic damage that accompanies some forms of hemosiderosis would seem to be unrelated to LTCC or TTCC, but rather to other routes of iron ingress present in heart cells.

show abstract

“…Variations in compensatory mechanisms and alternative metabolic pathways which are in operation in affected cells and tissues may contribute to minimising the severity of FA [85] . Similar variations are observed in other inherited and metabolic diseases including TM and hereditary haemochromatosis [13,62,[85][86][87] . Deficit of frataxin is mostly related to many abnormalities associated with mitochondrial structure and function.…”

Section: Ataxiasupporting

confidence: 50%

Transition of Thalassaemia and Friedreich ataxia from fatal to chronic diseases

Kolnagou

Kontoghiorghe

Kontoghiorghes

2014

WJM

Self Cite

View full text Add to dashboard Cite

Author contributions: Kolnagou A reviewed the organisational health structure of thalassaemia and Friedreich ataxia in Cyprus; Kontoghiorghe CN contributed the literature background on recent developments on thalassaemia and Friedreich ataxia and critically reviewed the clinical and other aspects of the manuscript; Kontoghiorghes GJ designed, wrote and edited the manuscript including the mechanisms of iron chelation therapy and iron metabolism and toxicity. AbstractThalassaemia major (TM) and Friedreich's ataxia (FA) are autosomal recessive inherited diseases related to the proteins haemoglobin and frataxin respectively. In both diseases abnormalities in iron metabolism is the main cause of iron toxicity leading to increased morbidity and mortality. Major efforts are directed towards the prevention of these diseases and also in their treatment using iron chelation therapy. Both TM and FA are endemic in Cyprus, where the frequency per total population of asymptomatic heterozygote carriers and patients is the highest worldwide. Cyprus has been a pioneering nation in preventing and nearly eliminating the birth of TM and FA patients by introducing an organized health structure, including prenatal and antenatal diagnosis. Effective iron chelation therapy, improved diagnostic methods and transfusion techniques as well as supportive therapy from other clinical specializations have improved the survival and quality of life of TM patients.Despite the tiresome clinical management regimes many TM patients are successful in their professional lives, have families with children and some are now living well into their fifties. The introduction of deferiprone led to the elimination of cardiac failure induced by iron overload toxicity, which was the major cause of mortality in TM. Effective combinations of deferiprone with deferoxamine in TM patients caused the fall of body iron to normal physiological ranges. In FA different mechanisms of iron metabolism and toxicity apply to that of TM, which can be targeted with specific iron chelation protocols. Preliminary findings from the introduction of deferiprone in FA patients have increased the hopes for improved and effective therapy in this untreatable condition. New and personalised treatments are proposed in TM and FA. Overall, advances in treatments and in particular of chelation therapy using deferiprone are transforming TM and FA from fatal to chronic conditions. The paradigm of Cyprus in the prevention and treatment of TM can be used for application worldwide.© 2014 Baishideng Publishing Group Inc. All rights reserved.Key words: Thalassaemia; Friedreich ataxia; Prenatal diagnosis; Survival; Chelation therapy; Deferiprone; Deferoxamine; Cyprus Core tip: Thalassaemia major (TM) and Friedreich's ataxia (FA) are inherited diseases related to iron toxicity, with high morbidity and mortality rates. Cyprus has the highest frequency of TM and FA worldwide. Prenatal diagnosis and other health policies almost abolished the birth of TM and FA patients in Cyprus. Deferiprone has increa...

show abstract

Efficacy, Compliance And Toxicity Factors Are Affecting The Rate Of Normalization Of Body Iron Stores In Thalassemia Patients Using The Deferiprone And Deferoxamine Combination Therapy

Cited by 30 publications

References 25 publications

Determinants of Pulmonary Hypertension in Patients with Beta-Thalassemia Major and Normal Ventricular Function

Determinants of Pulmonary Hypertension in Patients with Beta-Thalassemia Major and Normal Ventricular Function

Iron Overload and Apoptosis of HL-1 Cardiomyocytes: Effects of Calcium Channel Blockade

Transition of Thalassaemia and Friedreich ataxia from fatal to chronic diseases

Contact Info

Product

Resources

About