Amsterdam, The Netherlands, June 13-16, 2019
renal insufficiency. Furthermore, the question raises if the TRP metab-
Downloaded from https://journals.lww.com/hemasphere by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD3YiN3qTGLcvJT1mQ7InUm16+rwBU2Uhr2xoYv/Xgve+viszHs1CqSpQ== on 08/12/2019
ferritin < 12ng/ml in children aged <5 years, or ferritin <15ng/ml in
olism has a potential link to iron deficiency (ID) or iron deficiency ane-
mia (IDA). This issue is not covered in the current literature.
Aims: This prospective study aimed at evaluating the potential associa-
tion between iron metabolism and hemoglobin (Hb) concentrations and
the TRP metabolism in a large cohort of patients sub-grouped by the
presence or absence ID or anemia.
Methods: In this prospective study, 430 patients, who were admitted
by general practitioners and specialists to the outpatient clinic of the
Institute of Clinical Chemistry and Laboratory Medicine of the General
Hospital Steyr (Steyr, Austria) for a medical check-up of their actual iron
status, were included. All participants provided their written informed
consent. They underwent venous blood sampling after an overnight fast-
ing state in the morning (between 8.00 and 10.00 a.m.). The samples
were used to investigate the iron metabolism (i.e., Hb, mean corpus-
cular volume [MCV], mean corpuscular hemoglobin [MCH], ferritin,
transferrin saturation [TSAT], serum iron, transferrin, soluble transfer-
rin receptor [sTfR], reticulocyte hemoglobin [CHr]), and also the TRP
metabolism (TRP, kynurenine [KYN], kynurenic acid [KYNA], KYN/
TRP ratio, KYNA/KYN index). Serum concentrations of TRP, KYN,
and KYNA were measured by high-pressure liquid-chromatography
Results: Serum TRP, KYN and KYNA concentrations were positively
correlated with Hb (p-values <0.001, 0.029, and <0.001) and ferritin
(p-values 0.033, 0.008, and <0.001) measurements. In total, 159 pa-
tients with ID had significantly lower median (interquartile range) TRP
(58.5 [52.8 – 64.8] vs. 61.1 [54.5 – 66.4] µmol/L, p = 0.008) and KYNA
serum concentrations (27.8 [20.4 – 34.5] vs. 33.6 [25.4 – 43.9] µmol/L,
p <0.001) compared to 271 individuals without ID. Six patients with
anemia of chronic disease (ACD) showed the lowest median TRP con-
centration and the highest KYN/TRP ratio compared to 11 individuals
with iron deficiency anemia (IDA) and 413 non-anemic patients (p- val-
ues 0.001 and 0.011), respectively.
Summary/Conclusion: Parameters of TRP metabolism correlated with
Hb concentrations and iron metabolism. Individuals with ID or anemia
were found with significantly lower TRP values compared to individuals
without ID or anemia. These findings suggest an association between
TRP and iron metabolism. However, the authors of this work propose
performing prospective longitudinal studies to assess the clinical course
of associations between iron and TRP metabolism.
PS1293  OSTEOGENESIS IMPERFECTA: A NEW
UNRECOGNIZED ETIOLOGY FOR FUNCTIONAL IRON
DEFICIENCY
S. Elsayed 1, I. Ragab 2,*, A. Yacoup 3, M. Sallam 4
medical Genetics, Ain Shams University, Faculty of Medicine, 2Pediatric
1 related to IO.
Hematology Oncology, Ain Shams University, Faculty of Medicine,Children s
Hospital, Hematology Oncology Unit, 3Pediatrics, 4Clinical Pathology, Ain Shams
University, Faculty of Medicine, Cairo, Egypt
Background: Osteogenesis imperfecta (OI) is a genetic disorder of con-
nective tissue primarily affecting bone with a wide spectrum of clinical
expression that varies from death in the perinatal period to normal life
expectancy. Although data is scarce, we observed a high frequency of
anemia in patients with OI and hypothesized that functional iron defi-
ciency (FID) may occur secondary to the inflammation resulting from
frequent fractures and multiple surgical procedures.
Aims: The aim of this work was to study the frequency of anemia in
children with OI and try to classify them according to iron status by
conventional tests to analyze the possibility of presence of FID and the
possible association of hepcidin level with such etiology.
Methods: A cross-sectional study included 56 patients diagnosed with
osteogenesis imperfecta regularly following at the genetics clinic, Chil-
dren’sHospital, Ain-Shams university. All patients were subjected to
detailed clinical scoring with complete blood count, serum iron, serum
ferritin, and total iron binding capacity, C-reactive protein (CRP) and
serum hepcidin by ELISA, Dexa scan and lateral and AP spine x-ray.
Patients were classified into five groups, Group-1 including 7 OI pa-
tients fulfilling criteria of FID; serum ferritin > 100ng/ml, TS < 20%
and CRP> 1 mg/dl, Group-2 including 27 OI patients fulfilling criteria
of combined ACD&IDA; serum ferritin level was ≤ 100ng /ml, TS <
20% and CRP> 1 mg/dl, Group-3 including 16 OI patients without
anemia according to WHO classification, other anemia group includ-
ing 6 OI patients with anemia that could not be classified according
to the classification adopted in this study, IDA anemia including zero
OI patients as there were no patients fulfilling criteria of pure IDA;
| 2019;3:S1
children aged > 5 years, when the corresponding CRP was <1 mg/dl
and TS < 20%.
Results: The frequency of anemia among the studied patients with oste-
ogenesis imperfecta was 71.4%.Combined IDA and FID formed 48.2%,
12.5%, 28.6% and 10.7% hadFID, no anemia and other anemia groups
respectively. functional iron deficiency was found in 60.7%.
Median hepcidin level was significantly increased in pure FID patients
120 (100 – 510 ng/mL) as compared to those in no anemia patients 80
(65 – 100 ng/mL) and other anemias 60 (50 – 70 ng/mL). The serum
hepcidin concentration was mildly reduced in ACD patients with ID
with a median of 100 (60 – 150 ng/mL).
Patients with severity score levels less than 70% had significant higher
number of WBCS, platelets and serum hepcidin levels and significant
lower serum iron compared to patients with severity score levels more
than 70% and less than 90%.
Summary/Conclusion: Anemia is an unrecognized complication in pa-
tients with OI. Functional iron deficiency constitutes a significant etiol-
ogy adding to dietetic problems. New therapeutic approach for FID is
suggested to improve the quality of fracture healing in such group.
PS1294  MULTIFACTORIAL HEPCIDIN SUPPRESSION IN BETA-
THALASSEMIA CARRIERS WITH IRON OVERLOAD
F. Busti 1,*, G. Marchi 1, A. Castagna 1, A. Lira Zidanes 1, E. Nemeth 2,
T. Ganz 2, D. Girelli 1
Department of Medicine, University of Verona, Verona, Italy, 2UCLA Center for Iron
1
Disorders, Los Angeles, United States
Background: Beta-thalassemia carriers (βTc) can develop iron over-
load (IO), although infrequently. Traditional risk factors (alcohol abuse
or liver diseases) usually contribute, but sometimes IO remains unex-
plained. Hepcidin suppression and associated IO in βT major and inter-
media 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 hep-
cidin suppression in βTc with iron overload.
Methods: We characterized βT c 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 Gen-
eration Sequencing (NGS) analysis of a customized panel of genes
Results: Alcohol abuse was the main explanation for IO in 32% of cas-
es. 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 alco-
hol 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 lev-
els (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 mark-
ers of erythropoietic activity: EPO (R = 0.693; p = 0.001) and soluble
transferrin receptor (R = 0.716; p = 0.001).
Summary/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.
PS1295  IRON IN THE HUMAN HEARTS: DISTRIBUTION AND
ASSOCIATION WITH R2* VALUES BY CMR
A. Meloni 1,*, A. Maggio 2, V. Positano 1, A. Angelini 3, M. C. Putti 3,
E. Maresi 4, A. Pucci 5, C. Basso 3, F. Leto 2, M. Perazzolo 3, L. Pistoia 1,
A. Pepe 1
1
Fondazione G. Monasterio CNR-Regione Toscana, Pisa, 2Ospedale ‘’V. Cervello“,
Palermo, 3University of Padua Medical School, Padova, 4University of Palermo,
Palermo, 5University of Pisa, Pisa, Italy
591