Relationship between labile plasma iron, liver iron concentration and cardiac response in a deferasirox monotherapy trial

Wood, John C.; Glynos, Tara; Thompson, Alexis A.; Giardina, Patricia-Jane; Harmatz, Paul; Kang, Barinder; Paley, Carole; Coates, Thomas D.

doi:10.3324/haematol.2010.032862

Cited by 37 publications

(41 citation statements)

References 19 publications

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“…34,38 High liver iron (15-20 mg/g dry weight) damages liver parenchyma and increases circulating NTBI levels dramatically. 36,39,40 Therefore, the penalty for chelator noncompliance increases at high LICs. 10,36 LIC values below 5 mg/g can facilitate cardiac iron clearance with deferoxamine and deferasirox 10,31 ; however, no liver iron can be considered "safe" from a cardiac and endocrine perspective and extrahepatic monitoring by MRI is essential.…”

Section: Mri Assessment Of Liver Ironmentioning

confidence: 99%

“…32 Whereas NTBI is the likely the causal agent for extrahepatic iron deposition, it is not currently a useful clinical monitoring technique because it represents only a single "snapshot" of chelation compliance. 36 The ability of cardiac MRI to: (1) detect insidious, preclinical cardiac iron accumulation; (2) ensure completion of cardiac iron removal with intensified therapies; and (3) compare the relative cardiac efficacies of different chelators and chelation strategies, has improved patient safety and comfort at our institution and others. Some investigators also directly attribute improved patient survival in recent years to increasing MRI availability, 37 although the introduction of oral chelation and combination therapies certainly plays a role in improved outcomes as well.…”

Section: Impact Of Mri Iron Imaging On Patient Managementmentioning

confidence: 99%

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Impact of Iron Assessment by MRI

Wood

2011

Hematology

120

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The use of magnetic resonance imaging (MRI) to estimate tissue iron was conceived in the 1980s, but has only become a practical reality in the last decade. The technique is most often used to estimate hepatic and cardiac iron in patients with transfusional siderosis and has largely replaced liver biopsy for liver iron quantification. However, the ability of MRI to quantify extrahepatic iron has had a greater impact on patient care and on our understanding of iron overload pathophysiology. Iron cardiomyopathy used to be the leading cause of death in thalassemia major, but is now relatively rare in centers with regular MRI screening of cardiac iron, through earlier recognition of cardiac iron loading. Longitudinal MRI studies have demonstrated differential kinetics of uptake and clearance among the difference organs of the body. Although elevated serum ferritin and liver iron concentration (LIC) increase the risk of cardiac and endocrine toxicities, some patients unequivocally develop extrahepatic iron deposition and toxicity despite having low total body iron stores. These observations, coupled with the advent of increasing options for iron chelation therapy, are allowing clinicians to more appropriately tailor chelation therapy to individual patient needs, producing greater efficacy with fewer toxicities. Future frontiers in MRI monitoring include improved prevention of endocrine toxicities, particularly hypogonadotropic hypogonadism and diabetes.

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Section: Mri Assessment Of Liver Ironmentioning

confidence: 99%

Section: Impact Of Mri Iron Imaging On Patient Managementmentioning

confidence: 99%

Impact of Iron Assessment by MRI

Wood

2011

Hematology

120

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“…19 Studies in patients with various iron-loading disorders have shown reductions in NTBI and LPI upon phlebotomy and chelation therapy and that these reductions are associated with an improved prognosis. 2,3,[20][21][22][23] The results of NTBI and LPI assays are, therefore, promising as therapeutic targets and for the evaluation of iron overload and the efficacy of and compliance with iron-lowering therapies. 5,13,24 Due to the complexity and potential clinical importance of NTBI, several assays have been developed for its detection.…”

Section: Introductionmentioning

confidence: 99%

Second international round robin for the quantification of serum non-transferrin-bound iron and labile plasma iron in patients with iron-overload disorders

Swart¹,

Hendriks²,

Vorm³

et al. 2015

Haematologica

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N on-transferrin-bound iron and its labile (redox active) plasma iron component are thought to be potentially toxic forms of iron originally identified in the serum of patients with iron overload. We compared ten worldwide leading assays (6 for non-transferrinbound iron and 4 for labile plasma iron) as part of an international interlaboratory study. Serum samples from 60 patients with four different iron-overload disorders in various treatment phases were coded and sent in duplicate for analysis to five different laboratories worldwide. Some laboratories provided multiple assays. Overall, highest assay levels were observed for patients with untreated hereditary hemochromatosis and β-thalassemia intermedia, patients with transfusion-dependent myelodysplastic syndromes and patients with transfusion-dependent and chelated β-thalassemia major. Absolute levels differed considerably between assays and were lower for labile plasma iron than for non-transferrin-bound iron. Four assays also reported negative values. Assays were reproducible with high between-sample and low withinsample variation. Assays correlated and correlations were highest within the group of non-transferrin-bound iron assays and within that of labile plasma iron assays. Increased transferrin saturation, but not ferritin, was a good indicator of the presence of forms of circulating nontransferrin-bound iron. The possibility of using non-transferrin-bound iron and labile plasma iron measures as clinical indicators of overt iron overload and/or of treatment efficacy would largely depend on the rigorous validation and standardization of assays. Second international round robin for the quantification of serum non-transferrin-bound iron and labile plasma iron in patients with iron-overload disorders

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“…After cessation of chelation therapy, LPI quickly recovers to pretreatment levels 12. LPI exposure increases with liver iron concentration 13 meaning that patients with higher liver iron stores are likely to have a worse cardiac outcome following noncompliance with chelation (as with this case). Data from the UK Thalassemia register 14, 15 show that the mortality from beta‐thalassemia has fallen in the past two decades, mainly due to a reduction in deaths from cardiac iron overload.…”

Section: Discussionmentioning

confidence: 91%

Acute cardiac decompensation in a patient with beta‐thalassemia and diabetes mellitus following cessation of chelation therapy

Lioudaki

Whyte

2016

Clinical Case Reports

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Key Clinical MessagePatients with higher liver iron stores are likely to have a worse cardiac outcome following noncompliance with chelation. Cardiovascular magnetic resonance identifies myocardial siderosis allowing optimization of iron chelation regimes. Diabetes puts thalassemic patients at increased risk of myocardial fibrosis. Dual chelation therapy with deferoxamine and deferiprone offers improved cardiac outcomes.

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Relationship between labile plasma iron, liver iron concentration and cardiac response in a deferasirox monotherapy trial

Cited by 37 publications

References 19 publications

Impact of Iron Assessment by MRI

Impact of Iron Assessment by MRI

Second international round robin for the quantification of serum non-transferrin-bound iron and labile plasma iron in patients with iron-overload disorders

Acute cardiac decompensation in a patient with beta‐thalassemia and diabetes mellitus following cessation of chelation therapy

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