|
 
 |
| ORIGINAL ARTICLE |
|
| Year : 2023 | Volume
: 14
| Issue : 1 | Page : 28-34 |
|
Correlation of Erythroferrone and Hepcidin Hormones with Iron Status Levels in Patients with Iron Deficiency
Tiba Sabah Talawy1, Sunil Kumar Bylappa2, Marwan Ismail1, Praveen Kumar Kandakurti3, Aji Gopakumar4, Asaad Ma Babker1
1 Department of Medical Laboratory Sciences, College of Health Sciences, Gulf Medical University, Ajman, UAE
2 Anatomic Pathology Specialist and Lecturer, Thumbay Labs, Gulf Medical University, Ajman, UAE
3 Dean College of Health Sciences, Gulf Medical University, Ajman, UAE
4 Statistical Specialist, Research Section, Data and Statistics Department, Emirates Health Services (EHS), Healthcare Sector, Dubai, UAE
| Date of Submission | 25-Jul-2022 |
| Date of Decision | 25-Oct-2022 |
| Date of Acceptance | 08-Nov-2022 |
| Date of Web Publication | 17-Feb-2023 |
Correspondence Address:
Dr. Asaad Ma Babker
Department of Medical Laboratory Sciences, College of Health Sciences, Gulf Medical University, Ajman
UAE
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/joah.joah_63_22
INTRODUCTION: Iron-deficiency anemia (IDA) can be grouped under low hepcidin and high erythroferrone (ERFE) anemia. There is a negative correlation between ERFE and hepcidin, irrespective of the type of anemia. ERFE is a mediator of the response to erythropoietic stress, suppressing hepcidin to promote the mobilization of stored iron and the absorption of dietary iron.
OBJECTIVE: The objective was to determine the effect of ERFE hormone on hepcidin level as iron metabolism regulator in patients with iron deficiency (ID).
METHODS: The study included 50 female patients with ID who were investigated for complete blood count, serum levels of ferritin, and serum levels of iron using automated hematology, immunology, and chemistry analyzer. ERFE and hepcidin were measured by a specific enzyme-linked immunosorbent assay kit.
RESULTS: The serum ERFE levels were higher than normal in all cases and were negatively correlated with serum hepcidin (r = −0.023). In IDA, serum ERFE concentration had a nonsignificant negative correlation with hemoglobin (Hb) concentration. Serum hepcidin concentration had a nonsignificant negative correlation with Hb concentration. Serum ERFE had a nonsignificant negative correlation with Hb% in severe IDA (r = −0.679; P = 0.094) and mild IDA (r = −0.068; P = 0.789). ERFE had a nonsignificant positive correlation with Hb% in moderate IDA (r = 0.069; P = 0.793). Serum hepcidin had a nonsignificant positive correlation with Hb% in severe IDA (r = 0.036; P = 0.939). Serum hepcidin had a nonsignificant negative correlation with Hb% in mild IDA (r = −0.079; P = 0.764) and moderate IDA (r = −0.179; P = 0.491).
CONCLUSIONS: The potential of ERFE and hepcidin in diagnosing and categorizing ID disorders is promising. Understanding the mechanism of ERFE/hepcidin interaction will help in developing ERFE-/hepcidin-targeted therapies.
Keywords: Anemia, erythroferrone, erythropoiesis, hepcidin, iron-deficiency anemia
How to cite this article:
Talawy TS, Bylappa SK, Ismail M, Kandakurti PK, Gopakumar A, Babker AM. Correlation of Erythroferrone and Hepcidin Hormones with Iron Status Levels in Patients with Iron Deficiency. J Appl Hematol 2023;14:28-34 |
How to cite this URL:
Talawy TS, Bylappa SK, Ismail M, Kandakurti PK, Gopakumar A, Babker AM. Correlation of Erythroferrone and Hepcidin Hormones with Iron Status Levels in Patients with Iron Deficiency. J Appl Hematol [serial online] 2023 [cited 2023 Apr 1];14:28-34. Available from: https://www.jahjournal.org/text.asp?2023/14/1/28/369842 |
| Introduction | |  |
Iron-deficiency anemia (IDA) refers to microcytic hypochromic anemia, that is, a condition mainly caused by insufficient levels of iron in the body, resulting in reduced hemoglobin (Hb) synthesis.[1] IDA can result from inadequate iron intake, decreased iron absorption, increased iron demand, and increased iron loss.[2] Hepcidin hormone is predominately expressed in the hepatic tissue and regulates iron metabolism by controlling iron absorption and distribution in various tissues. Hepcidin causes degradation of ferroportin, the only recognized exporter of cellular iron, leading to the retention of iron in macrophages and the reduction in serum iron concentration.[3] Erythroferrone (ERFE) is a glycoprotein hormone produced by erythroblasts in response to erythropoietin that acts directly on the liver to inhibit the production of hepcidin, leading to increased iron delivery for intensified activity of erythropoiesis.[4] ERFE is a mediator of the response to erythropoietic stress, suppressing hepcidin to promote the mobilization of stored iron and the absorption of dietary iron. ERFE inhibits hepcidin synthesis by binding bone morphogenetic proteins and thereby inhibiting the bone morphogenetic protein pathway that controls hepcidin expression.[5] Dysregulation of hepcidin production leads to various iron disorders, including iron overload in hereditary hemochromatosis, iron-loading anemia, anemia of inflammation, and IDA.[6] Till now, few studies are conducted on humans regarding the role of ERFE during iron deficiency (ID), and most studies are conducted on animals. Defining the mechanisms of this dysregulation is vital for understanding the pathogenesis of common conditions associated with disordered iron metabolism and erythropoiesis activity. Stress erythropoiesis causes the suppression of hepcidin to increase iron availability for Hb synthesis. The erythroid hormone ERFE was identified as the mediator of this process. The current study aimed to estimate ERFE and hepcidin hormones and correlate to iron status parameters levels in patients with ID.
| Materials and Methods | | |
This study was approved by the Ethical Committee of the Gulf Medical University, and informed consent was obtained from each participant included in the study. Fifty iron-deficient female patients were included in the study from Thumbay Hospitals and Thumbay Labs, GMU, Ajman, UAE, between January 2021 and April 2021. For the diagnosis of ID and anemia, laboratory investigation and family history were noted for each participant. For the diagnosis of anemia, we have used the WHO criteria for Hb% to classify anemia levels into severe, moderate, and mild. Moreover, for the diagnosis of ID, we have analyzed serum ferritin and serum iron, as well as complete blood count (CBC) to evaluate red blood cells (RBCs) indices and platelets counts. Peripheral blood smear was also prepared to evaluate RBCs morphology.
Analytical procedures
Two milliliters (ml) of blood in one ethylenediaminetetraacetic acid (EDTA) Vacutainer and two plain tubes with 2 ml of blood in each were taken. EDTA sample was utilized for performing CBC and evaluating Hb%, RBC count, total white blood cells (WBCs), platelet count, RBCs indices, and RDW. CBC was performed using Beckman Coulter (UniCel DxH 800/900) automated hematology analyzer. Beckman Coulter (UniCel DxH 800/900) hematology analyzer is a five-part autoanalyzer with Coulter and impedance principle. Serum iron was measured by Beckman Coulter DXC AU 700 analyzer based on the colorimetric method and ferritin by Beckman Coulter DxI 800 based on the immunoenzymatic (sandwich) assay. The analysis of ERFE and hepcidin was conducted using semiautomated Tecan instrument, by enzyme-linked immunosorbent assay (ELISA) method, after thawing the samples. Serum ERFE was measured by a specific ELISA kit (MyBioSource, Inc., California, USA, Catalog No. MBS2088219) following the manufacturer's instructions. This ELISA kit has a detection range of 0.156–10 ng/mL with an intra-assay and inter-assay precision: CV <10% and <12%, respectively. The samples for ERFE were processed as per the kit insert instructions. Serum hepcidin was measured by a specific ELISA kit (MyBioSource, Inc., California, USA, Catalog No. MBS733228) following the manufacturer's instructions. The data collected for the study were fed to the Excel spreadsheet, and statistical analysis was performed using SPSS-27 version. The significance level was set at P ≤ 0.05.
| Results | | |
The study included 50 participants. We used the reference ranges for all parameters according to Thumbay Medicity, Ajman, UAE [Table 1]. The iron deficiency status was determined by the percentage of Hb which was over 12g/dL for those who did not have IDA and below 12 g/dL for those who did have IDA. The lowest Hb was 6.1g/dL, while the highest was 13.4 g/dL. All participants were women, and their age ranged from 19 to 50 years. Their body mass index (BMI) ranged from 17.6 to 36.8, and with the median BMI being 23.5, most of them were healthy, neither overweight nor underweight. The WBC and platelet count parameters are normal. Serum hepcidin was minimum at 0.4 ng/ml and maximum at 2.6 ng/ml, while serum ERFE ranged from 2.2 ng/ml to 39.0 ng/ml [Table 2]. About 88% of the participants had abnormal serum iron, 95.2% had abnormal serum ferritin, and 100% had abnormal serum ERFE [Table 3]. The data indicate that the discriminative ability of the clinical parameters “serum ERFEand serum hepcidin and H:E” in identifying normal (12–15 mg/dl) and low abnormal level of Hb is poor. Area under the ROC Curve (AUC) is seen to be <=0.7, indicating a poor diagnostic ability. Among the three clinical tests, serum hepcidin has a better diagnostic ability, followed by hepcidin/erythroferrone (H:E) ratio [Figure 1]. | Table 1: Reference ranges for all parameters according to Thumbay Medicity, Ajman, UAE
Click here to view |
 | Table 3: Distribution of parameters in patients with iron-deficiency anemia (n=42)
Click here to view |
 | Figure 1: ROC curves for hepcidin, ERFE, and HE ratio for diagnostic ability of low hemoglobin percentage. ROC = Receiver operating characteristic; HE = Hepcidin/erythroferrone; ERFE = Erythroferrone
Click here to view |
The data demonstrate that the discriminative ability of the clinical parameters “serum ERFE and serum hepcidin and H:E” in identifying normal (13.0–150.0 ng/ml) and abnormal level of ferritin is acceptable. AUC is seen to be >=0.7, indicating an acceptable diagnostic ability. AUC is seen to be <=0.7, indicating a poor diagnostic ability [Figure 2]. The data demonstrate that the discriminative ability of the clinical parameters “serum ERFE and serum hepcidin and H:E” in identifying normal (60–180 μg/ml) and abnormal level of iron is poor. AUC is seen to be <=0.7, indicating a poor diagnostic ability [Figure 3]. The correlation between ERFE and hepcidin is negative. Whenever ERFE increases, the hepcidin level decreases. However, it was a weak negative correlation [Table 4]. In severe IDA, serum ferritin shows a significant (P = 0.05) positive correlation (0.739), while serum ERFE shows a nonsignificant (P = 0.094) moderate negative correlation (−0.679). In moderate IDA, serum iron and serum hepcidin exhibit a nonsignificant positive correlation; serum iron, serum ferritin, and serum ERFE exhibit a nonsignificant positive correlation. Serum hepcidin shows a nonsignificant negative correlation. In mild IDA, serum iron and serum ferritin show a nonsignificant positive correlation, whereas serum hepcidin and serum ERFE show a nonsignificant negative correlation. In normal group, serum ferritin reveals a significant (P = 0.016) strong positive correlation, while serum iron and serum hepcidin reveal a nonsignificant positive correlation. In addition, serum ERFE shows a nonsignificant negative correlation in all groups except in moderate IDA. Serum hepcidin shows a nonsignificant negative correlation in mild and moderate ID and a nonsignificant positive correlation in severe IDA and normal group [Table 5]. | Figure 2: ROC curves for hepcidin, ERFE, and HE ratio for diagnostic ability of low serum ferritin. ROC = Receiver operating characteristic; HE = Hepcidin/erythroferrone; ERFE = Erythroferrone
Click here to view |
 | Figure 3: ROC curves for hepcidin, ERFE, and HE ratio for diagnostic ability of low iron. ROC = Receiver operating characteristic; HE = Hepcidin/erythroferrone; ERFE = Erythroferrone
Click here to view |
 | Table 4: Correlation of the level of serum iron, ferritin, and hepcidin with erythroferrone hormone
Click here to view |
 | Table 5: Correlation of red blood cells indices (red blood cells, hemoglobin, mean corpuscular hemoglobin, mean corpuscular volume, mean corpuscular hemoglobin concentration, and platelets counts) with erythroferrone levels
Click here to view |
| Discussion | | |
The current study investigates the role of ERFE, a biological mediator of hepcidin during erythropoiesis, in ID status of iron-deficient patients, as well as evaluated iron parameters (serum iron and ferritin), RBC parameter, ERFE, and hepcidin in different stages of ID. The levels of ERFE and hepcidin had a nonsignificant weak negative correlation. ERFE was found to be substantially related to the indicators of iron metabolism (Hb, mean corpuscular volume [MCV], mean corpuscular hemoglobin [MCH], and MCH concentration [MCHC]) in both ID status and IDA patients [Table 5]. In both ID status and anemia cases, a nonsignificant weak negative correlation was identified in the above-mentioned parameters. All the ERFE levels observed in 50 patients were higher than normal, demonstrating that ERFE could be a better indicator for detecting ID status and anemia [Table 6]. | Table 6: Correlation between the level of serum iron, ferritin, hepcidin, and erythroferrone hormone in different stages of iron deficiency
Click here to view |
The high levels of hepcidin are not only just responsible for regulating the expression of iron already stored in the body but they also affect the RBC cycle – erythropoiesis.[7] In patients with IDA, hepcidin may consequently be a crucial controller of iron homeostasis during the process of erythropoiesis.[8] Hepcidin has been shown in multiple studies to be a reliable indicator for measuring iron release and storage in anemic patients.[9] Erythropoietic demand controls hepcidin expression, which controls iron uptake.[10] Hepcidin suppresses the intracellular iron transporter ferroportin,[11],[12] resulting in decreased iron regeneration by splenic lymphocytes and dietary iron absorption by enterocytes. Hepcidin is repressed to facilitate iron mobilization for enhanced erythropoiesis when iron is essential following an episode of acute loss of blood or due to ischemia.[13]
In the present study, we noticed a negative correlation between serum ERFE levels and Hb%, serum iron, and serum ferritin and a positive correlation between ERFE and platelet counts, proven by El Gendy et al., who observed a negative correlation between serum ERFE concentrations and Hb level, serum iron, transferrin saturation, and serum ferritin and a positive correlation between serum ERFE concentrations and TIBC (total iron-binding capacity) in IDA patients.[6] However, the difference is that our current study was carried out on adults while El Gendy et al.'s study was on pediatric patients. This comparison is used because no prior studies are available to date to evaluate the role of ERFE on hepcidin in IDA patients in the adults' group. The present study reveals a significant positive correlation of HCT, MCV, MCH, MCHC, iron, and ferritin with Hb levels in IDA patients. Meanwhile, serum hepcidin with Hb levels shows a nonsignificant (P = 0.784) weak negative correlation (r = −0.04), which was not considered an expected result for this study, and this might be due to the smaller number of samples or due to some patients interfering factors. For this, we recommend a larger sample size to confirm the correlation between hepcidin and Hb levels since this correlation is not significant in this study. On the other hand, serum ERFE with Hb levels reveals a nonsignificant (0.393) moderate negative correlation (−0.135). RDW-SD and PLT show a nonsignificant weak negative correlation, while MPV, WBC, uWBC, and RBC show a nonsignificant weak positive correlation with Hb [Table 5].
In the current study, we investigated the role of ERFE and hepcidin in different stages of ID and observed that serum ERFE shows a nonsignificant negative correlation in all groups except in moderate IDA. Meanwhile, serum hepcidin shows a nonsignificant negative correlation in mild and moderate ID, but a non-significant positive correlation in severe IDA and the normal Hb group. Since no previous studies applied this comparison, we recommend conducting further studies with a larger sample size to determine the role of ERFE and hepcidin in different stages of ID. A study by Cuves et al.[14] demonstrated a median value of ERFE of 0.48 ng/ml for 30 female healthy individuals, which falls within our reference range adapted in our study. A study by Del Orbe Barreto et al. evaluated hepcidin and ERFE levels in different erythroid disorders using the five groups of patients.[15] The median values of Hb, ferritin, hepcidin, and ERFE in the healthy controls group of Barreto et al. are matched within the reference range adapted in our study. We compared relevant parameters (median values of Hb, ferritin, hepcidin, and ERFE) of their two groups, which are the healthy groups (n = 26) and the IDA group (n = 9), with our ID status group, iron-deficient anemia group, and moderate anemia subgroup. The median value of hepcidin in the IDA group of Barreto et al.'s study is 1.00 ng/ml, which is in comparison with our findings in the IDA group (1.11 ng/ml) and in the moderate anemia group (1.13 ng/ml). These values are lower than the reference range and comparable to one another in terms of clinical decisions. A similar comparison for median values of ERFE with Barreto et al. revealed that ERFE is low in IDA (0.118 ng/ml) compared to our IDA group (3.48 ng/ml) and the moderate anemia group (3.81 ng/ml). The ERFE value in Barreto et al.'s study of 0.118 ng/ml falls within the normal range (0.01–0.76 ng/ml), in contrast to our study where the values are above the reference range supporting the role in hepcidin suppression. The negative correlation of low hepcidin and high ERFE is maintained in our study groups, including the ID status group. The ferritin in both studies and all ID groups is on the lower side.
We compared the correlation of serum ERFE and hepcidin in a study conducted by Smesam et al.[9] on transfusion-dependent beta-thalassemia patients (-0.23) with our study (−0.27). Hepcidin and ERFE are negatively correlated in our study, as well as in the study by Semesam et al. Although the pathogenesis of anemia is different in these studies, the negative correlation is maintained in both, where one is ID and the other is ineffective erythropoiesis. The correlation of ERFE with iron (0.18) and ferritin (0.15) is positive in Smesan et al.'s transfusion-dependent beta-thalassemia study and negative in IDA in our study (ERFE with iron [−0.139] and ferritin [−0.104]), substantiating the iron status and the pathogenesis. In beta-thalassemia serum, iron and ferritin are normal or elevated, and ERFE is also elevated due to ineffective erythropoiesis, in contrast with IDA where ERFE is elevated, and serum iron and ferritin decreased. ROC curve analysis for ERFE in detecting beta-thalassemia major in Smesan et al.'s transfusion-dependent beta-thalassemia study indicates AUC of 0.924. In this study, the detecting ability of low serum ferritin by ERFE indicates AUC of 0.729, which shows that ERFE is a reliable indicator for IDA as well as in beta-thalassemia.[16] ROC curves were also utilized for analyzing ERFE, hepcidin, and H:E in detecting low Hb% and low serum iron in our study. Among ERFE, hepcidin, and H:E, serum hepcidin had a better diagnostic ability to detect low Hb%. H:E ratio had a better diagnostic ability to detect low serum iron (AUC: 0.519). H:E ratio has been used as a biomarker in other studies, like in pregnancy to detect adverse outcomes (AUC: 0.86), where it is found to be significant.[17] Kautz et al. reportedly recognized ERFE as a major modulator of iron homeostasis during stress erythropoiesis by reducing hepcidin production during stress erythropoiesis.[18] This study raises the concerns regarding the significance of this novel erythroid hormone in hepcidin suppression in the various kinds of anemia. Since there have been no early cases on the correlation between human serum ERFE and iron status parametric levels in instances of IDA in adult patients, the focus of this research was to show the relationship between serum ERFE and iron status parameters levels in this common form of anemia. There were no earlier publications on plasma ERFE levels in IDA in adult patients, although Mirciov et al. conducted a trial demonstrating a significant elevation in bone marrow and splenic ERFE production in IDA in wild-type mice.[19] In conditions of iron insufficiency, the elevated ERFE output and observed relationships with iron parameters can be described as a regulatory technique to promote hepcidin inhibition and so enhance iron bioavailability. Earlier observations of elevated blood concentrations of erythropoietin and in turn increased the levels of ERFE production by erythroid progenitors in IDA[20] corroborate our findings. The recommended therapy for IDA is to find the cause and take iron supplementation. Conversely, in certain situations, therapy can fail due to significant adverse events or refractoriness to iron therapy. In cases of iron-restricted erythropoiesis, a deeper knowledge of the various iron-hepcidin effector pathways may lead to new treatment alternatives.[21],[22] Our other suggestions are to expand the study to include a larger number of patients of various ages, as well as to estimate blood iron status markers, hepcidin, and ERFE levels for all participants at the same time. Soon, developing a validated reliable assay for estimating human serum ERFE levels and standardizing the reference range in healthy persons of various ages would be a big undertaking. As of now, it is unclear how hepcidin will affect the existing iron indices. Clinical populations have not studied the diagnostic characteristics of blood hepcidin concentration as an indicator of ID, and studies have not included enough healthy and iron-deficient individuals to estimate a reference range for the test. Various cutoffs for serum hepcidin in diagnosing iron insufficiency remain to be identified. There are some limitations in the current study as follows: The study had only a small number of cases. The time duration for the study was short. All the participants were female. Moreover, we faced some difficulties in the kits for testing hepcidin and ERFE; they were difficult to procure as these are research kits.
| Conclusion | | |
The determination of the accurate role and relationship between ERFE and hepcidin and between different parameters will help in differentiating and categorizing the stages of IDA and various types of anemia. This will result in a better diagnosis and better options for treatment. The findings of our study will help generate hypotheses for further studies with a larger sample sizes to envisage the clinical utility of EFRFE and hepcidin.
Future recommendations
We recommend using large sample sizes to obtain accurate statistics, defining reference range for the current geographic distribution by including both male and female patients, and learning the interaction between hepcidin and ERFE in infections/inflammation, including new emerging disease, COVID-19, where serum ferritin is raised as an acute-phase reactant. Hepcidin and ERFE will be helpful as new markers, not only for IDAs but also for better treatment strategies in other diseases.
Acknowledgments
This publication was supported by the College of Health Sciences, Gulf Medical University, Ajman, UAE.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
| References | | |
| 1. | Almousawi AS, Sharba IR. Erythroferrone Hormone a novel biomarker is associated with anemia and iron overload in beta thalassemia patients. J Phys 2019;1294.  |
| 2. | Robach P, Gammella E, Recalcati S, Girelli D, Castagna A, Roustit M, et al. Induction of erythroferrone in healthy humans by micro-dose recombinant erythropoietin or high-altitude exposure. Haematologica 2021;106:384-90. |
| 3. | Arezes J, Foy N, McHugh K, Quinkert D, Benard S, Sawant A, et al. Antibodies against the erythroferrone N-terminal domain prevent hepcidin suppression and ameliorate murine thalassemia. Blood 2020;135:547-57. |
| 4. | Nemeth E, Ganz T. The role of hepcidin in iron metabolism. Acta Haematol 2009;122:78-86. |
| 5. | Anderson GJ, Frazer DM. Current understanding of iron homeostasis. Am J Clin Nutr 2017;106:1559S-1566S. |
| 6. | El Gendy FM, El-Hawy MA, Shehata AM, Osheba HE. Erythroferrone and iron status parameters levels in pediatric patients with iron deficiency anemia. Eur J Haematol 2018;100:356-60. |
| 7. | Kuragano T, Shimonaka Y, Kida A, Furuta M, Nanami M, Otaki Y, et al. Determinants of hepcidin in patients on maintenance hemodialysis: Role of inflammation. Am J Nephrol 2010;31:534-40. |
| 8. | Zumbrennen-Bullough K, Babitt JL. The iron cycle in chronic kidney disease (CKD): From genetics and experimental models to CKD patients. Nephrol Dial Transplant 2014;29:263-73. |
| 9. | Smesam HN, Albuthabhak HA, Arjmand S, Al-Hakeim HK, R Siadat SO. Evaluation of erythroferrone, hepcidin, and iron overload status in Iraqi transfusion-dependent β-thalassemia major patients. Hemoglobin 2020;44:272-7. |
| 10. | Ganz T. Hepcidin and iron regulation, 10 years later. Blood 2011;117:4425-33. |
| 11. | Nemeth E, Tuttle MS, Powelson J, Vaughn MB, Donovan A, Ward DM, et al. Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science 2004;306:2090-3. |
| 12. | Aschemeyer S, Qiao B, Stefanova D, Valore EV, Sek AC, Ruwe TA, et al. Structure-function analysis of ferroportin defines the binding site and an alternative mechanism of action of hepcidin. Blood 2018;131:899-910. |
| 13. | Gardenghi S, Grady RW, Rivella S. Anemia, ineffective erythropoiesis, and hepcidin: Interacting factors in abnormal iron metabolism leading to iron overload in β-thalassemia. Hematol Oncol Clin North Am 2010;24:1089-107. |
| 14. | Ramirez Cuevas K, Schobinger C, Gottardo E, Voss SC, Kuuranne T, Tissot JD, et al. Erythroferrone as a sensitive biomarker to detect stimulation of erythropoiesis. Drug Test Anal 2020;12:261-7. |
| 15. | |
| 16. | Saad H, Bahgat S, El Dewy D, Galal R. Erythroferrone Level in β-thalassemia Patients. J Recent Adv Med 2021;2:1-9. |
| 17. | Wei S, Liu W, Qi Y, Guo Y, Zhang S, Wang L, et al. Disordered serum erythroferrone and hepcidin levels as indicators of the spontaneous abortion occurrence during early pregnancy in humans. Br J Haematol 2021;192:643-51. |
| 18. | Kautz L, Jung G, Du X, Gabayan V, Chapman J, Nasoff M, et al. Erythroferrone contributes to hepcidin suppression and iron overload in a mouse model of β-thalassemia. Blood 2015;126:2031-7. |
| 19. | Mirciov CS, Wilkins SJ, Dunn LA, Anderson GJ, Frazer DM. Characterization of putative erythroid regulators of hepcidin in mouse models of anemia. PLoS One 2017;12:e0171054. |
| 20. | Ramu R, Narayana Murthy C. Study of iron deficiency anemia with thrombocytosis in association with serum erythropoietin levels. Trop J Path Micro 2017;3:71-6. |
| 21. | De Falco L, Sanchez M, Silvestri L, Kannengiesser C, Muckenthaler MU, Iolascon A, et al. Iron refractory iron deficiency anemia. Haematologica 2013;98:845-53. |
| 22. | Bayraktar UD, Bayraktar S. Treatment of iron deficiency anemia associated with gastrointestinal tract diseases. World J Gastroenterol 2010;16:2720-5. |
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]
|
Search Pubmed for