Iron Overload and Iron Chelation Therapy in Thalassaemia and Sickle Cell Haemoglobinopathies

Pippard, Martin J.

doi:10.1159/000205876

Cited by 27 publications

(19 citation statements)

References 28 publications

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“…When patients with iron overload are admitted to hospital with noninfectious complaints, we often give deferoxamine 3 grams in 500 mL normal saline intravenously over 24 hours, repeating continuously during their stay. Giving Vitamin C 250 mg orally daily while the patient is on deferoxamine increases iron excretion [107, 108]. Ongoing cohort studies should help define the natural history of iron overload in sickle cell patients [109–111].…”

Section: Gastrointestinal/hepatobiliary Complicationsmentioning

confidence: 99%

Beyond the Definitions of the Phenotypic Complications of Sickle Cell Disease: An Update on Management

Ballas

Kesen

Goldberg

et al. 2012

The Scientific World Journal

158

144

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The sickle hemoglobin is an abnormal hemoglobin due to point mutation (GAG → GTG) in exon 1 of the β globin gene resulting in the substitution of glutamic acid by valine at position 6 of the β globin polypeptide chain. Although the molecular lesion is a single-point mutation, the sickle gene is pleiotropic in nature causing multiple phenotypic expressions that constitute the various complications of sickle cell disease in general and sickle cell anemia in particular. The disease itself is chronic in nature but many of its complications are acute such as the recurrent acute painful crises (its hallmark), acute chest syndrome, and priapism. These complications vary considerably among patients, in the same patient with time, among countries and with age and sex. To date, there is no well-established consensus among providers on the management of the complications of sickle cell disease due in part to lack of evidence and in part to differences in the experience of providers. It is the aim of this paper to review available current approaches to manage the major complications of sickle cell disease. We hope that this will establish another preliminary forum among providers that may eventually lead the way to better outcomes.

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Section: Gastrointestinal/hepatobiliary Complicationsmentioning

confidence: 99%

Beyond the Definitions of the Phenotypic Complications of Sickle Cell Disease: An Update on Management

Ballas

Kesen

Goldberg

et al. 2012

The Scientific World Journal

158

144

View full text Add to dashboard Cite

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“…In another study, marked iron overload was found in the liver, spleen, and kidney with complete absence of iron in the bone marrow despite elevated ferritin. Pippard et al [54] have hypothesized that SCD patients have a significantly different clinical course compared with β-thalassemia patients because their iron stores remain locked in a non-toxic form in RE system macrophages longer than in β-thalassemia patients. In a 1994 review, the authors suggested that SCD patients may be at significantly less risk of iron overload because of the pathologic iron deposition induced by inflammation in SCD [55].…”

Section: Basic Iron Metabolism In Scdmentioning

confidence: 99%

Iron Metabolism and Iron Chelation in Sickle Cell Disease

Walter¹,

Harmatz²,

Vichinsky³

2009

Acta Haematol

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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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“…33 Iron chelation therapy with intravenous or subcutaneous deferoxamine is recommended, as untreated, this condition can progress to hepatic fibrosis and cirrhosis. 44 …”

Section: Sickle Cell Intra-hepatic Cholestasismentioning

confidence: 99%