scholarly journals POS0567 HEPCIDIN IS POTENTIAL BIOMARKER TO DISTINGUISH BETWEEN IRON DEFICIENCY ANEMIA AND ANEMIA OF INFLAMMATION IN RHEUMATOID ARTHRITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 518.2-518
Author(s):  
E. Galushko ◽  
A. Semashko ◽  
A. Gordeev ◽  
A. Lila

Background:Anemia of inflammation (AI) and iron deficiency anemia (IDA) are the two most prevalent forms of anemia in patients with rheumatoid arthritis (RA). Diagnosis becomes challenging if AI is associated with true ID (AI/ID), as there is still a lack of a gold standard for differentiation between AI and AI/ID. However, as therapies to overcome anemia differ, proper diagnosis and understanding of underlying pathophysiological regulations are necessary.Objectives:The aim of the study was to evaluate the clinical efficiency of hepcidin, a key regulator of iron metabolism, in the diagnosis of IDA, as well as the differential diagnosis of AI/ID and AI in patients with RA.Methods:The study was undertaken 96 patients with RA, 67 of them were diagnosed anemia according to WHO criteria (104,3±21,4 g/l). Anemic patients and anemia-free patients with RA (n=29) were comparable (p>0.05) in age (44.4±14.8 and 49.8±9.3 years), disease duration (73.5±65.4 and 59.8±48.3 months) and DAS28 (6.3±1.6 and 5.9±1.9). All cases were subjected to following tests: complete blood count with peripheral smear, serum C-reactive protein, serum interleukin-6, iron studies, serum soluble transferrin receptor (sTfR), and serum hepcidin. Patients with RA and anemia were divided two groups: 25 patients with IDA and 42 - with AI. The AI cases were subdivided into pure AI and AI with coexistent ID (n=15).Results:The mean serum hepcidin concentration was significantly increased in pure AI patients (123.85±25.8 ng/mL) as compared to those in IDA patients (63.9±22.8 ng/mL, P < 0.05) and anemia-free patients with RA (88.1±39.09 ng/mL). Also, compared to pure AI patients [normal sTfR levels (<3 µg/mL)], the serum hepcidin concentration was reduced significantly in AI patients with ID [high sTfR levels (≥3 µg/mL)] with a mean of 79.0±23.97 ng/mL.Conclusion:Hepcidin measurement can provide a useful tool for differentiating AI from IDA and also help to identify an iron deficiency in AI patients. This might aid in the appropriate selection of therapy for these patients.Disclosure of Interests:None declared

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 944-944 ◽  
Author(s):  
Kanuri Giridhar ◽  
Sawhney Ritica ◽  
Chichula Deepti ◽  
Arun S Shet

Abstract INTRODUCTION: The etiology of HIV- associated anemia is multifactorial. We previously found a high prevalence of anaemia of inflammation and anemia due to micronutrient deficiencies in HIV patients (Eur J Pediatr 2012, 17:531). Inflammatory disease confounds the value of standard diagnostic markers, posing a challenge to the detection of iron deficient and iron-restricted erythropoiesis. Using serum hepcidin as a biomarker, we tested the hypothesis that total body iron stores like inflammatory signals would also influence serum hepcidin levels in patients with HIV infection. METHODS: Healthy subjects, patients with pure iron deficiency anemia (IDA) andpatients with HIV infection were prospectively enrolled after obtaining informed consent. Using sex adjusted WHO values for anemia diagnosis, ferritin <12µg/L, and CRP values, subjects were categorized into healthy and IDA groups (N Engl J Med 2015, 373:485). Using age adjusted WHO values for anemia, patients with HIV were divided into anemic and non-anemic groups. Using the soluble transferrin receptor (sTfR)/log ferritin (F) index, we defined those subjects with an sTfR-F index < 1.03 as having anemia of inflammation (AI) and those subjects with an sTfR-F index ≥1.03 as having IDA superimposed on AI (Am J Hematol. 2011, 86:923). All laboratory analytes were measured using standard commercial assays. RESULTS: The demographic characteristics of the different groups in the study population are shown in table 1. Compared with healthy controls, mean hemoglobin was significantly lower in patients with pure IDA, HIV patients with anemia, and HIV patients without anemia (p<0.001). The serum soluble transferin receptor (sTfR) levels and serum erythropoietin levels were significantly elevated in pure IDA patients (p<0.001) and HIV patients with anemia (p<0.001) compared with healthy controls, reflecting erythropoietic stress. Compared with healthy controls, serum hepcidin levels were markedly lower in pure IDA patients (p<0.01) and HIV patients with anemia suggesting that iron status influenced hepcidin levels more profoundly than inflammation in HIV infected patients. We also measured erythrocyte ZPP levels and found them to be significantly higher in pure IDA patients (p<0.001) and HIV patients with anemia (p<0.001) compared to healthy controls. All HIV patients with anemia had an sTfR-F index ≥1.03 suggesting the presence of IDA superimposed on AI. Interestingly, serum hepcidin levels correlated inversely with the sTfR-F index in both patients with pure IDA (ρ=-0.76; p<0.001) and in HIV patients with anemia (ρ=-0.4; p<0.02). Similarly, ZPP levels correlated linearly with the sTfR-F index in pure IDA patients (ρ=0.6; p<0.002) and in HIV patients with anemia (ρ=0.5; p<0.001). CONCLUSION: Our data shows significant differences in serum hepcidin and erythrocyte ZPP levels in healthy, IDA and HIV patients. These two biomarkers could be included in the panel of diagnostic tests used to detect iron deficiency anemia superimposed on anemia of inflammation. Further studies are needed to provide the appropriate cut-off values with which IDA can be detected with appropriate sensitivity and specificity in patients with anemia of inflammation. Such data may also be helpful in monitoring therapeutic responses to iron. Table 1. Haematological and biochemical parameters Healthy(n = 45) Pure IDA(n=33) HIV with anemia(n=46) HIV without anemia(n=46) Age ± SD 31±7.5 25±3.6 35±11.9 39±12 Hemoglobin ± SD(g/dl) 15.2±1.2 10.1±1.3a, c, d 11±1.1a, d 13.8±1.3a MCV ± SD 85±4.2 74±7.7 80±8.7 85±4.6 Biochemical parameters Serum Ferritin*(ng/mL) 57 (43, 83) 4.5a, c, d (3.1, 7) 14a, d (7, 34) 47 (32, 130) Serum sTfR*(mg/L) 1.7b, c (1.3, 2) 4.3 (3, 6.3) 2.5 (2, 3.7) 1.8b, c (1.3, 2.1) Serum Erythropoietin*(mU/mL) 6.5b, c (4.9, 9.8) 40 (28, 61) 20b (13, 32) 10b, c (5, 14) Biomarkers Serum Hepcidin*(ng/mL) 20.6 (14.2, 25.6) 0.5a (0.1, 3.3) 11.6b (2.9, 29.8) Erythrocyte ZPP*(μmol/mol heme) 50b, c (40, 58) 200 (117, 247) 101b (69, 131) 56b, c (42, 75) *All non Gaussian distributed data are presented as median (25th percentile, 75th percentile); ap < 0.05 compared with healthy subjects, bp < 0.05 compared with pure IDA patients, cp < 0.05 compared with HIV anemia patients, dp < 0.05 compared with HIV without anemia patients. Disclosures No relevant conflicts of interest to declare.


Author(s):  
Sajjad H. Naqvi ◽  
Syed Faizan-ul-Hassan Naqvi ◽  
Iftikhar H. Naqvi ◽  
Muhammad Farhan ◽  
Tanveer Abbas ◽  
...  

Author(s):  
Manal Mahmoud Atia ◽  
Rasha Mohamed Gama ◽  
Mohamed Attia Saad ◽  
Mohammed Amr Hamam

Greater prevalence of iron deficiency (ID) has been observed in overweight and obese children and adolescents. Hepcidin acts as a key regulator of iron metabolism. Hepcidin synthesis increases in response inflammatory cytokines especially Interleukin-6 (IL-6). Considering that obesity represents a low grade chronic inflammatory state, a high concentration of hepcidin has been found in obese children. Elevated hepcidin level in obese children is associated with diminished response to oral iron therapy. Lactoferrin is an iron-binding multifunctional glycoprotein and has strong capacity to modulate the inflammatory response by its capacity to reduce pro-inflammatory cytokine expression in vivo, including IL-6 and hepcidin. Aim of the Work: To compare the efficacy of lactoferrin versus oral iron therapy in treatment of obese children and adolescents with iron deficiency anemia and the effect of therapy on serum hepcidin and interleukin 6 levels. Methodology: This prospective randomized clinical trial was conducted on 40 obese children and adolescents aged between 6 –18 years suffering from iron deficiency anemia (IDA). They were equally randomized into one of 2 groups. Group A received regular oral lactoferrin in a dose of 100 mg/day. Group B received regular oral iron supplementation (Ferric hydroxide polymaltose) in a dose of 6 mg elemental iron/kg /day.Baseline investigations included complete blood count (CBC), iron profile (Serum ferritin, serum iron, total iron binding capacity (TIBC), transferrin saturation), serum Interleukin 6, and serum hepcidin. Reevaluation of CBC was done monthly while iron status parameters, serum IL-6 and serum hepcidin were reevaluated after 3 months of receiving regular therapy. Results: Significant elevations in hemoglobin, MCV, MCH, Serum ferritin, serum iron and transferrin saturation with lactoferrin therapy compared to oral iron therapy. Significantly Lower TIBC after 3 months of lactoferrin therapy while the decrease in TIBC was insignificant in the iron therapy group.Lower serum hepcidin and IL6 after 3 months of lactoferrin therapy with no significant change in serum hepcidin and IL6 after iron therapy. Conclusion: This study clearly demonstrated the superiority of lactoferrin over iron use as oral in the treatment of iron deficiency anemia in obese children not only for the better response of hematological and iron status parameters and less gastrointestinal side effects but also for its effect on decreasing inflammatory biomarkers as hepcidin and IL6.


QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Mahmoud Mohamed Zaki Ali ◽  
Maha Abd ElMoniem Behairy ◽  
Reem Mohsen El Sharabasy ◽  
Ahmed Hamed Ahmed Gharib

Abstract Background Hepcidin has long been postulated as a key regulatory peptide in iron homeostasis. Its reduced clearance and elevated levels in hemodialysis (HD) patients lead to functional iron deficiency (FID) and ESA resistance. Vitamin C may be used as adjuvant therapy in FID anemia, but there are limited studies investigating the direct relation between vitamin C and hepcidin levels in HD patients. We aimed to test the reducing effect of Oral vitamin C therapy on hepcidin levels among hemodialysis patients with functional iron deficiency anemia. Patients and Methods This study is an open label randomized controlled clinical trial. It was conducted in the hemodialysis units of Ain Shams University hospitals. 48 adult prevalent HD patients were included and were divided into two groups. Group 1 (study group) included 31 patients who received the conventional treatment of erythropoietin stimulating agents (ESAs) together with oral supplementation of vitamin C 500 mg every other day for 3 months in addition to IV iron therapy. Group 2 (control group) included 17 patients who received only the conventional therapy of ESAs according to their hemoglobin (Hb) levels in addition to IV iron therapy. Laboratory parameters including serum hepcidin levels, highly sensitive CRP (hs-CRP) titer, CBC, kidney function tests and iron indices were measured at the baseline of the study and after 3 months. Results Oral vitamin C therapy resulted in a statistically significant reduction in both hepcidin and hs-CRP levels in the study group after 3 months. The study group showed a significant reduction in serum iron and ferritin levels (P &lt; 0.05). A Decrease in EPO requirements and elevation of hemoglobin level were observed in the study group but were not statistically significant as a short term effect of oral vitamin C, in comparison to the control group. A highly significant correlation was observed between serum hepcidin and hs-CRP (R=0.46, P&lt;0.01). Conclusion Oral vitamin C may be a promising therapy in decreasing serum hepcidin and hs-CRP levels in prevalent hemodialysis patients with functional iron deficiency anemia.


QJM ◽  
2020 ◽  
Vol 113 (Supplement_1) ◽  
Author(s):  
R A R Ahmed ◽  
M H A Fayek ◽  
D A D Salem

Abstract Background Anemia is a significant worldwide health problem. Approximately one third of the world's population suffers from anemia, half of which is due to iron deficiency (ID). Evaluation of parameters relating to serum ferritin and iron is critically important in the diagnosis of iron deficiency anemia (IDA). The recent development of automated systems for hematology analysis has made it possible to measure reticulocyte hemoglobin equivalent (RET-He), which is thought to reflect iron content in reticulocytes, in the same sample used for complete blood count tests. Aim of the work We aimed to assess the role of RET- He in diagnosis of iron deficiency anemia. Subjects and Methods Blood samples were obtained from 102 subjects. Patients were classified into three groups: IDA, ID, and anemia of chronic disorder (ACD). In addition 20 age and sex matched healthy volunteers were enrolled as control. RET- He was assessed by Sysmex XN1000 hematology analyzer. Results Patients in the IDA group had significantly lower RET-He levels than those in the control group. RET-He was correlated with serum ferritin in the IDA and ID groups. The area under the curve for RET-He was 0.883. The cut-off value of RET- He for detecting IDA was ≤ 26.5 pg with 80% sensitivity and 90% specificity. Conclusion RET-He facilitates the diagnosis of IDA with high accuracy and may be a clinically useful marker for determining IDA.


2019 ◽  
Vol 5 (3) ◽  
pp. eaav9020 ◽  
Author(s):  
Andrew M. Prentice ◽  
Amat Bah ◽  
Momodou W. Jallow ◽  
Amadou T. Jallow ◽  
Saikou Sanyang ◽  
...  

Iron deficiency anemia (IDA) is the most prevalent nutritional condition worldwide. We studied the contribution of hepcidin-mediated iron blockade to IDA in African children. We measured hepcidin and hemoglobin weekly, and hematological, inflammatory, and iron biomarkers at baseline, 7 weeks, and 12 weeks in 407 anemic (hemoglobin < 11 g/dl), otherwise healthy Gambian children (6 to 27 months). Each child maintained remarkably constant hepcidin levels (P < 0.0001 for between-child variance), with half consistently maintaining levels that indicate physiological blockade of iron absorption. Hepcidin was strongly predicted by nurse-ascribed adverse events with dominant signals from respiratory infections and fevers (all P < 0.0001). Diarrhea and fecal calprotectin were not associated with hepcidin. In multivariate analysis, C-reactive protein was the dominant predictor of hepcidin and contributed to iron blockade even at very low levels. We conclude that even low-grade inflammation, especially associated with respiratory infections, contributes to IDA in African children.


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5387-5387
Author(s):  
Eun Sil Park ◽  
In-Suk Kim ◽  
Jae-Young Lim

Abstract Backgroud . The aims of this study were to measure the serum levels of prohepcidin in anemic and non anemic infants and to evaluate the correlation between prohepcidin and iron parameters and inflammatory cytokines. Procedure. One hundred and sixty nine patients aged from 6 months to 24 months were enrolled and divided into 4 groups according to hemoglobin and serum ferritin (SF). Routine hematologic labs, soluble transferrin receptor (sTfR), serum prohepcidin, C reactive protein (CRP), and interleukin-6 (IL-6) were assessed. The subgroup of anemia of inflammation (AI) was defined as Hb &lt;11 g/dL and SF &gt;50 μg/L, the subgroup of iron deficiency anemia (IDA) as Hb &lt;11 g/dL and SF &lt;12 μg/L, the normal group as Hb ≥11 g/dL and SF ≥12 μg/L, and the unclassified anemia group (UCA) as &lt;11 g/dL and SF 12–50 μg/L. Results. The prohepcidin levels ranged from 38.86 to 874.25 ng/mL throughout all the infants (258.60±130.03 ng/mL) but were significantly lower in the AI group than in the normal group (201.93±71.74 vs 299.97±120.68 ng/mL, P=0.007). However there was no significant difference between anemic subgroups. Prohepcidin levels were positively correlated with CRP (r=0.400, P=0.048) in the AI group and were negatively correlated with sTfR in the UCA group (r=−0.376, P=0.022). However in both groups there were no independent predictors in multiple regression analysis. Conclusions. This study examines the prohepcidin levels in infants with anemia and without anemia. The prohepcidin levels of anemic infants were significantly lower than those of infants without anemia. However there was no correlation between prohepcidin and inflammatory cytokines or iron parameters in the groups of AI and IDA, thus we cannot differentiate between them using prohepcidin levels.


Anemia ◽  
2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Betelihem Terefe ◽  
Asaye Birhanu ◽  
Paulos Nigussie ◽  
Aster Tsegaye

Iron deficiency anemia among pregnant women is a widespread problem in developing countries including Ethiopia, though its influence on neonatal iron status was inconsistently reported in literature. This cross-sectional study was conducted to compare hematologic profiles and iron status of newborns from mothers with different anemia status and determine correlation between maternal and neonatal hematologic profiles and iron status in Ethiopian context. We included 89 mothers and their respective newborns and performed complete blood count and assessed serum ferritin and C-reactive protein levels from blood samples collected from study participants. Maternal median hemoglobin and serum ferritin levels were 12.2 g/dL and 47.0 ng/mL, respectively. The median hemoglobin and serum ferritin levels for the newborns were 16.2 g/dL and 187.6 ng/mL, respectively. The mothers were classified into two groups based on hemoglobin and serum ferritin levels as iron deficient anemic (IDA) and nonanemic (NA) and newborns of IDA mothers had significantly lower levels of serum ferritin (P=0.017) and hemoglobin concentration (P=0.024). Besides, newborns’ ferritin and hemoglobin levels showed significant correlation with maternal hemoglobin (P=0.018;P=0.039) and ferritin (P=0.000;P=0.008) levels. We concluded that maternal IDA may have an effect on the iron stores of newborns.


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