Reversal of cardiac complications in thalassemia major by long‐term intermittent daily intensive iron chelation

Miskin, Hagit; Yaniv, Isaac; Berant, Michael; Hershko, C; Tamary, Hannah

doi:10.1034/j.1600-0609.2003.00075.x

Cited by 53 publications

(52 citation statements)

References 13 publications

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“…This can be explained as the earliest echocardio graphic studies were conducted before current standard subcutaneous and intensive intravenous DFO regimens were available that used neither chelation nor sub therapeutic doses of DFO [13]. From this study we conclude that LVEF measurement associated with serum ferritin assay decreased incidence of CHF in patients with βTM in our hospital as it directs the use of intensive chelation therapy.…”

Section: Discussionmentioning

confidence: 59%

“…DFO treatment was intensified in the event of objective evidence of asymptomatic LV dysfunction at rest to prevent progression to frank CHF or in case of CHF. Treatment was intensified using 24-hour continuous intravenous infusion of DFO (100 mg/kg) diluted in 500 to 1000 mL normal saline and delivered though a peripheral vein [13] for up to 1 week at a time to supplement ongoing subcutaneous treatment. Dosing intensification was reduced as serum ferritin values decreased in line with the therapeutic index, as previously describe [13].…”

Section: Methodsmentioning

confidence: 99%

“…Assessment myocardial iron and function by MRI has revolutionized the treatment of βTM patients and allows recognition of preclinical myocardial iron, stratifies prospective cardiac risk, and tracks response to modifications in iron chelation therapy [12]. This triggered us to evaluate the protocol applied in KAUH where the sequential quantification of ventricular function annually and in association with serum ferritin assay every 3 months is usedto identify early changes in the left ventricular ejection fraction (LVEF) from baseline for each patient which could be used for identifying patients at high risk and indicate the need for intensive chelation therapy.…”

Section: Introductionmentioning

confidence: 99%

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Potential effect of β thalassemia major on cardiac function among patients in Jeddah, Saudi Arabia

Alama¹,

Hindawi²,

Sayes³

et al. 2017

Med Res Innov

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The present studydetect the prevalence of cardiac complications and the efficacy of iron overload monitoring by ECHO (LVEF), and serum ferritin assay in patients at Department of Clinical Hematology with β thalassemia major (βTM). Case records of all βTM patients were analyzed for clinical data, age, sex, heart failure, serum ferritin, ECG, chest x-ray and echocardiography. Sixty -two βTM patients with serially recorded LVEF are included in statistical analysis. Age range of these patients was 4-36 years. Clinical congestive cardiac failure (CHF) was observed in 5 patients(6.45%) with the age range of 13-28 years, 34 patients (54.8%) have normal ECHO findings while 28 patients (45.2%) have valvular heart disease, 8 patients (12.6%) had tricuspid regurgitation with pulmonary hypertension, and 20 patients (32.2%) had tricuspid, mitral or aortic regurgitation. The present study indicated that Observation of excess iron in the heart of βTM patients in King Abdulaziz University Hospital (KAUH) through LVEF and serum ferritin analysis have reduced incidence of CHF. LVEF instructs the use of intensive chelation therapy but cannot prevent or predict heart damage or CHF in the course of the disease; this may be due to the poor prognosis once CHF is occurred. More sensitive methods for early detection of cardiac complication arerequired as MRI T2* which is used to estimate myocardial iron and identifies pre-clinical cardiac iron deposition to prevent irreversible cardiac complication.

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Section: Discussionmentioning

confidence: 59%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Potential effect of β thalassemia major on cardiac function among patients in Jeddah, Saudi Arabia

Alama¹,

Hindawi²,

Sayes³

et al. 2017

Med Res Innov

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show abstract

“…(20,21,22) Thus the accumulation of iron within myocytes is a problem of storage, only when this capacity is exceeded, or the cell subjected to stress do the harmful effects of iron become manifest, raising the possibility that removal of excess iron deposits has the potential to restore the cell to normality, an observation made clinically on numerous occasions. (23,24,25) …”

Section: Iron Toxicitymentioning

confidence: 99%

Thalassaemia Major and the Heart

Walker

2013

Thalassemia Reports

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“…Unfortunately, most patients develop adverse effects such as local irritation, skin redness and mild pain at the applied sites, as well as poor compliance treatment from DFO [7,8]. Other side effects involve GI disturbances, arthopathy, zinc deficiency, agranulocytosis and thrombocytopenia from DFP [9]; as well as renal toxicity and Fanconi syndrome in DFX treatment [10].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of a novel oral iron chelator 1-(N-acetyl-6-aminohexyl)-3-hydroxypyridin-4-one (CM1) for treatment of iron overload in mice

Srichairatanakool¹,

Pangjit²,

Phisalaphong³

et al. 2013

ABB

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Desferrioxamine (DFO), deferiprone (DFP) and deferasirox (DFX) are promising effective iron chelatorsfor the treatment of iron overload in -thalassemia patients; nonetheless, their side effects have also been reported. 3-Hydroxypyridinone derivatives are being developed as a safer new chelator and in combined chelation therapy. We evaluated the iron-chelating activity of 1-(N-acetyl-6-aminohexyl)-3-hydroxypyridin-4-one (CM1) in iron-loaded C57BL6 mice. The feeding of a ferrocene-supplemented diet (Fe diet) to mice resulted in iron overload, detectable plasma nontransferrin-bound iron (NTBI) and labile plasma iron (LPI), and increases of red cell membrane iron, plasma malondialdehyde (MDA) and excessive tissue iron deposits. Like DFP, the CM1 lowered the levels of the membrane non-heme iron, the NTBI and LPI (p < 0.05) and the MDA after 3 months of treatment. Administration of the Fe diet and the Fe diet along with the chelators did not change the morphology of the liver and heart. Numerous iron accumulations were observed in the liver and spleen tissues of the Fe dietfed mice, whereas the CM1 reduced such iron deposition. Thus, 1-(N-acetyl-6-aminohexyl)-3-hydroxypyridin-4-one (CM1) can be considered a candidate bidentate oral iron chelator and is effective in the removal of toxic irons in blood compartment and tissues. The effectiveness and toxicity of the CM1 need to be investigated extensively in thalassemia mice and patients with iron overload.

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Reversal of cardiac complications in thalassemia major by long‐term intermittent daily intensive iron chelation

Abstract: These results with the longest follow-up period in the literature suggest that i.v. high-dose DFO for 8-10 h daily may be as effective as continuous 24-h infusion for the reversal of established cardiac disease in TM.

Cited by 53 publications

References 13 publications

Potential effect of β thalassemia major on cardiac function among patients in Jeddah, Saudi Arabia

Potential effect of β thalassemia major on cardiac function among patients in Jeddah, Saudi Arabia

Thalassaemia Major and the Heart

Evaluation of a novel oral iron chelator 1-(N-acetyl-6-aminohexyl)-3-hydroxypyridin-4-one (CM1) for treatment of iron overload in mice

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