MULTIFACTORIAL HEPCIDIN SUPPRESSION IN BETA-THALASSEMIA CARRIERS WITH IRON OVERLOAD
Author(s): ,
Fabiana Busti
Affiliations:
Department of Medicine,University of Verona,Verona,Italy
,
Giacomo Marchi
Affiliations:
Department of Medicine,University of Verona,Verona,Italy
,
Annalisa Castagna
Affiliations:
Department of Medicine,University of Verona,Verona,Italy
,
Acaynne Lira Zidanes
Affiliations:
Department of Medicine,University of Verona,Verona,Italy
,
Elizabeta Nemeth
Affiliations:
UCLA Center for Iron Disorders,Los Angeles,United States
,
Tomas Ganz
Affiliations:
UCLA Center for Iron Disorders,Los Angeles,United States
Domenico Girelli
Affiliations:
Department of Medicine,University of Verona,Verona,Italy
EHA Library. Busti F. Jun 15, 2019; 266911; PS1294
Dr. Fabiana Busti
Dr. Fabiana Busti
Contributions
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Abstract

Abstract: PS1294

Type: Poster Presentation

Presentation during EHA24: On Saturday, June 15, 2019 from 17:30 - 19:00

Location: Poster area

Background

Beta-thalassemia carriers (βTc) can develop iron overload (IO), although infrequently. Traditional risk factors (alcohol abuse or liver diseases) usually contribute, but sometimes IO remains unexplained. Hepcidin suppression and associated IO in βT major and intermedia is, at least in part, dependent on the increased production of the hormone erythroferrone (ERFE), but the role of ERFE in βTc remains to be explored.

Aims
The aim of the study was to evaluate the factors involved in hepcidin suppression in βTc with iron overload. 

Methods
We characterized βTc patients (n=22, mean age 57±10 yrs; 73% males) referred to our center because of clinically relevant IO (mean ferritin 1115 ng/ml, CI95% 864-1437), confirmed by MRI and/or liver biopsy. In addition to clinical evaluation, we measured serum hepcidin, EPO, sTfR and ERFE, and performed Next Generation Sequencing (NGS) analysis of a customized panel of genes related to IO.

Results

Alcohol abuse was the main explanation for IO in 32% of cases. NGS identified 4 patients with HFE-hemochromatosis (HH) and 1 patient with a novel heterozygous mutation in BMP6. In 7 subjects we did not identify any single strong risk factor, but noted moderate alcohol consumption, the H63D variant in HFE, and/or some features of the metabolic syndrome. Most subjects (73%) had high or high-normal serum hepcidin (mean 11 nmol/l, CI95% 8-16), however, the hepcidin/ferritin ratio indicated a relative hepcidin suppression. Serum ERFE levels (mean 34 ng/ml, CI95% 21-55) were intermediate between healthy blood donors and βT major. Excluding patients with HH, we observed an inverse correlation between hepcidin and ERFE (β-coeff. -0.576; p=0.019). As expected, ERFE concentration strongly correlated with markers of erythropoietic activity: EPO (R=0.693; p=0.001) and soluble transferrin receptor (R=0.716; p=0.001).

Conclusion
IO in βTc represents a neglected condition. Mild ERFE-mediated hepcidin suppression could be aggravated by low-risk co-factors, such as H63D variant. Further investigations are needed to understand the role of individual factors involved in the development of IO in βTc.

Session topic: 29. Iron metabolism, deficiency and overload

Keyword(s): Erythropoieisis, Iron overload, Thalassemia

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