Ferritin Group Research Articles

Serum ferritin as a risk factor for type 2 diabetes mellitus, regulated by liver transferrin receptor 2.

ObjectiveThe aim of this study was to evaluate the effect of TFR2 on iron storage in type 2 diabetes.MethodsA cross-sectional study was conducted among 1938 participants from the Jiangchuan Community of Shanghai. A total of 784 participants with T2DM and 1154 normal participants (non-T2DM) were enrolled in this study. Serum ferritin, fasting blood glucose, postprandial blood glucose, and HbA1C (glycated hemoglobin A1c) levels were determined. Eighteen Wistar male rats were randomly assigned into three groups (n = 6/group): rats in a high-fat diet streptozotocin (HFD+STZ) group were fed with HFD for 4 weeks and intraperitoneally injected with streptozotocin (STZ); rats in a control group were fed with a standard diet for 4 weeks and intraperitoneally injected with buffer; rats in an STZ group were fed with a standard diet for 4 weeks and intraperitoneally injected with streptozotocin. Glucose tolerance test was performed at the end of the study. Blood samples and liver tissues were assessed for liver TFR2, blood glucose, serum ferritin, and iron levels.ResultsThe mean serum ferritin level of T2DM participants was significantly higher than that of the control group (227 (140–352) vs 203.5 (130.5–312) ng/mL, P < 0.05). Serum ferritin level was an independent risk factor for T2DM (high ferritin group vs low ferritin group, 1.304 (1.03–1.651), P < 0.05). Diabetic rats showed reduced liver TFR2 levels, with increased serum ferritin levels.ConclusionT2DM participants exhibited iron disorder with elevated serum ferritin levels. Elevated serum ferritin levels in diabetic rats were accompanied by reduced liver TFR2 levels.

Prognostic role of pre-operative serum ferritin level in stage 2 colon cancer.

In this study, we aimed to evaluate the prognostic value of preoperative serum ferritin level in patients with stage 2 colon cancer who underwent curative surgery. The data of 120 patients who were stage 2 after curative surgery and whose ferritin levels were measured at the time of diagnosis without starting any treatment were analyzed. Demographic data such as age and gender, histopathological characteristics such as tumor size, lymphovascular invasion (LVI), perineural invasion (PNI), number of removed lymph nodes, tumor grade, and clinical and laboratory data were retrieved from the hospital medical charts or electronic medical records. In the survival analysis, the cut-off level of ferritin was accepted as 150 ng/ml, which is the upper limit determined by the World Health Organization (WHO), as a prognostic factor. Fifty (41.7%) of the patients were female, 70 (58.3%) were male, and the median age was 63.5 (range 24-90) years. There was no significant difference between the low and high ferritin groups regarding age, gender, T stage, tumor localization, histological subtype, PNI, LVI, removal of less than 12 lymph nodes, and tumor size. Disease-free survival and overall survival of patients with high ferritin levels were worse than patients with low ferritin levels, but this difference did not reach statistical significance. Serum ferritin level is an easily monitored, cost-effective, and reproducible marker. İn this study we found that high ferritin level was associated with poor survival, although it was not statistically significant.

Genome-wide gene and serum ferritin interaction in the development of type 2 diabetes in adults aged 40 years or older

Background and aimsElevated serum ferritin is associated with incident Type 2 diabetes (T2D), but the interactions between serum ferritin and genetic factors which may improve understanding underlying mechanism in the development of T2D are still unclear. We determined the gene–ferritin interactions on the development of T2D by genome-wide gene–ferritin interaction analyses. Methods and resultsA total of 3405 participants from two prospective cohorts of community living residents were included, and the median follow-time was 3.99 years. Genome-wide gene–ferritin interactions were analyzed using the joint test with two degrees of freedom and the interaction test with one degree of freedom. There were 18 SNPs selected in the joint test. Finally, four independent variants [rs355140 (LINC00312), rs4075576 (nearby PDGFA), rs1332202 (PTPRD), and rs713157 (nearby LINC00900)] with low pairwise linkage disequilibrium (r2<0.2) and located at least 1000 kb from the index SNP showed interactions with serum ferritin level. In the association analyses between serum ferritin levels (tertiles of ferritin and ferritin status) and the incidence of T2D according to genotype, the Incidence Rate Ratios (IRRs) in the highest tertile of ferritin level (vs. the lowest tertile) were greater for participants with heterozygotes of risk alleles of each of the four SNP than IRRs for those with wild type. Compared with the normal group, the elevated ferritin group also had a higher risk of T2D for all genetic variants of risk alleles, particularly its homozygotes. ConclusionSerum ferritin level interacts with genetic variants (rs355140, rs4075576, rs1332202, and rs713157) in the development of T2D.

RELATION BETWEEN SERUM FERRITIN AND VISCERAL FAT MASS IN AIN SHAMS MEDICAL STUDENTS

Background: Adipocytes are not just storage organs for fat, they play a regulatory role in body homeostasis including iron metabolism. Concerns about the effect of visceral fat mass on serum ferritin has been raised as increase visceral fat mass accumulation may lead to sequestration of Fe within the reticuloendothelial system leading to decrease dietary Fe absorption from the intestineAim of the work: This study aims to detect relation between percentage of visceral fat mass and serum ferritin level in Sample of Ain Shams medical students.Patients and Methods: this was a case–control study conducted on 150 medical students over 3 months they were divided into two subgroups: normal serum ferritin group and low serum ferritin group. All students were subjected to the detailed history and 24 hour dietary recall, anthropometric measurements, complete blood picture, measurement of serum ferritin=Results: There were significantly negative association between visceral fat mass and serum ferritin also the serum ferritin showed significant positive correlations with BMI and waist hip ratio.Conclusion: Higher visceral fat mass levels should be taken into account when assessing body Fe status and should probably be treated before providing dietary recommendations to correct low serum ferritin level.

Association between HLA genotype and ferritin levels in COVID-19 infection: a study of a Saudi cohort

Background An elevation in serum ferritin levels through an unknown mechanism was observed in COVID-19 infected patients. This study examined the association between patients’ HLA genotype and serum ferritin level modulation and also assessed the effect of serum ferritin levels on infection severity/mortality. Materials and methods One hundred and thirty-six COVID-19 Saudi patients were divided into two groups according to their ferritin levels: group 1 (<500 ng/mL, N = 67) and group 2 (>500 ng/mL, N = 69). HLA genotyping (class I and II) was carried out through the rPCR-SSO method. Results High serum ferritin levels were associated with a significant increase in infection severity, as 75% of ICU patients showed high levels of ferritin compared to 43% of patients with moderate symptoms, p = .002. This elevation indicated a gender skew in that 56% of the infected male patients displayed high ferritin levels compared to 36.6% of the female patients, p = .03. In terms of mortality, 74% of patients with fatal outcomes had a high level of serum ferritin compared to 47% of recovered patients, p = .039. There was a significant difference in the HLA frequency between the two groups, with a predominance of HLA-A*01 in the low-ferritin group (19.4 vs. 6.5%, p = .002, pc = .016) and predominance of C*03 in the high ferritin group (10.9 vs. 3%, p = .047, pc = .27). Conclusion High serum ferritin levels are associated with an increase in COVID-19 severity, which may be affected by HLA polymorphism.

Investigation of Circulating Plasma Micro RNAs As Biomarkers for Iron Status in Blood Donors

Introduction: Ferritin is the major iron storage protein in the body and serum ferritin is the most widely used screening test both for iron deficiency and iron overload conditions. However, as ferritin is a positive acute phase response protein its usefulness is limited in the presence of either acute or chronic inflammation or liver disease. A more specific biomarker of iron status could therefore be of considerable value. MicroRNAs (miRNAs) are small non-coding RNA fragments that repress target gene expression post-transcriptionally within cells. MiRNAs can also be detected outside cells in various body fluids and these circulating forms may be useful as biomarkers for various pathological conditions. Studies indicate that certain miRNAs may play an important role in cellular processes regulating iron homeostasis including, miRNA-320 in post-transcriptional control of Transferrin Receptor 1 (TfR1) gene expression, and miR-200b in regulation of ferritin expression. The aim of this study was to determine whether circulating miRNAs in plasma could serve as biomarkers for iron status in healthy blood donors.Methods: Study participants were selected from new/active blood donors based on their latest historic ferritin results in the blood bank laboratory information system. Participants were divided into two groups, a) high ferritin (>150 μg/l, HF) and b) low ferritin (<15 μg/l, LF) arms. The study was divided into two phases; i) a pilot study (20 participants) and ii) a confirmation study (50 participants). After obtaining informed consent EDTA blood samples were collected and frozen plasma aliquots prepared by a standard method to minimize pre-analytical variation. Ferritin was measured in all participants with an automated immunoassay (Ortho Vitros®). Hepcidin and sTFR plasma levels were measured by ELISA (DRG Instruments GmbH) in the pilot study group to confirm iron status. MiRNA isolation and analysis was performed by a miRNA profiling service (Exiqon A/S, Vedbæk, Denmark). In the pilot-study 179 miRNAs were analyzed using commercially available qPCR assays (Serum/Plasma Focus Panel, Exiqon A/S). In the confirmation study a custom-made Pick-&-Mix miRNA qPCR panel was ordered including 13 candidate miRNAs chosen from the pilot-study data. Standard biostatistical methods were utilized for data analysis.Results: Serum ferritin measured on average 13.8 ± 3.8 μg/l in the pilot study low ferritin (LF) arm, compared to 231 ± 58.8 μg/l in the high ferritin (HF) group (p<0.001). Hepcidin plasma levels were markedly lower in the low ferritin (LF) arm compared to the high ferritin group (HF) (2.3 ± 0.6 vs. 17.8 ± 3.1 ng/ml, p<0.001) whereas sTfR1 levels were higher in the LF group (1.9 ± 0.4 vs. 1.1 ± 0.2 µg/ml, p<0,001) confirming the difference in iron status between the two groups. Quality control of raw miRNA qPCR data indicated good technical performance of the profiling experiments. In the pilot-study 106 of 179 miRNAs in the panel gave signals in all 20 samples and on average 153 miRNAs were detected in each sample. On unsupervised analysis by hierarchical clustering and principal component analysis (PCA) the samples did not cluster according to iron status (figure 1). When comparing HF vs. LF groups 17 miRNAs were found to be differentially expressed when using a significance level of 0.05, but only one assay (hsa-miR-34a-5p) passed Benjamini-Hochberg correction for multiple testing. However, this particular miRNA frequently gave low/absent signals in both groups and was not considered further. To confirm the findings of the pilot study thirteen miRNAs were chosen for a confirmation-study based on technical performance and expression in the pilot study. Unsupervised analysis of 50 samples did not reveal any difference in expression for the 13 selected miRNAs between the LF and HF groups. Furthermore, when comparing the two groups no miRNA was found to be differentially expressed when using a p-value cutoff of 0.05.Conclusion: These data do not suggest that those circulating plasma miRNAs analyzed by qPCR panels in this study should be considered promising biomarkers for iron status in healthy individuals. However, in the future, sensitive and comprehensive detection methods such as next-generation sequencing might reveal novel circulating miRNAs that correlate with iron stores. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Impact of age to ferritin and neutrophil-lymphocyte ratio as biomarkers for intensive care requirement and mortality risk in COVID-19 patients in Makassar, Indonesia.

Inflammation plays a substantial role in COVID‐19 pathophysiology. Ferritin and neutrophil‐lymphocyte ratio (NLR) are significant prognostic biomarkers used in COVID‐19 patients, although they are affected by other factors such as comorbidities and age. Aging changes the immune system through immunosenescence and inflammaging; however, there are limited number of studies evaluating its effect on ferritin and NLR as part of the complete assessment for intensive care requirement and mortality risk. A single‐center retrospective cohort study of 295 COVID‐19 patients was performed at the Siloam Hospitals Makassar, South Sulawesi, Indonesia from April to August 2020. After admission, all patients were followed up for clinical outcomes. Patients were grouped into strata based on age (<50 years vs. ≥50 years) and risk groups (low‐risk ferritin vs. high‐risk ferritin; low‐risk NLR vs. high‐risk NLR). The endpoints of the study were the intensive care requirements and mortality. Among the 295 COVID‐19 patients, 264 survived and 31 deceased. Ferritin and NLR had higher area under curve (AUC) values than other inflammatory parameters and had significantly different outcomes in both mortality and intensive care requirement groups. The combination of ferritin and NLR showed higher AUC values for intensive care requirement and mortality (AUC, 0.783; 95% confidence interval, 0.703–0.864). Multivariate analysis showed that both endpoints were strongly affected by age, ferritin level, and NLR. Age significantly multiplied clinical endpoints in low‐risk group patients but not in high‐risk group patients. The combination of ferritin and NLR had a better predictive value for intensive care requirement and mortality risk. However, age strongly affects clinical outcome in low‐risk groups of both ferritin and NLR groups; hence, it should be considered as an early predictive factor of COVID‐19 disease progression.

English

Serum ferritin has been proposed as a predictor of hepcidin concentrations in response to exercise. However, this fact has not been studied in physically-active women. Therefore, the main objective of this study was to analyse the hepcidin response at different ferritin status before and after running exercise in physically active females. Fifteen eumenorrheic women performed a 40-min running protocol at 75% of VO2peak speed in different menstrual cycle phases (early-follicular phase, mid-follicular phase and luteal phase). Blood samples were collected pre-exercise, 0h post-exercise and 3h post-exercise. For statistics, participants were divided into two groups according to their pre-exercise ferritin levels (&lt;20 and ≥20 μg/L). Through menstrual cycle, hepcidin was lower in both early follicular phase (p=0.024; 64.81±22.48 ng/ml) and mid-follicular phase (p=0.007; 64.68±23.91 ng/ml) for &lt;20 μg/L ferritin group, in comparison with ≥20 μg/L group (81.17±27.89 and 79.54±22.72 ng/ml, respectively). Hepcidin showed no differences between both ferritin groups in either pre-exercise, 0h post-exercise and 3h post-exercise. Additionally, no association between pre-exercise ferritin and hepcidin levels 3h post-exercise (r=-0.091; p=0.554) was found. Menstrual cycle phase appears to influence hepcidin levels depending on ferritin reserves. In particular, physically-active females with depleted ferritin reserves seems to present lower hepcidin levels during the early-follicular phase and mid-follicular phase. However, no association between ferritin and hepcidin levels was found in this study. Hence, ferritin levels alone may not be a good predictor of hepcidin response to exercise in this population. Multiple factors such as sexual hormones, training loads and menstrual bleeding must be taken into account.

Elevated serum ferritin level effectively discriminates severity illness and liver injury of coronavirus disease 2019 pneumonia

Aim Ferritin is a hepatic protein that plays vital roles in diagnosing and predicting diseases, but its potential in coronavirus disease 2019 (COVID-19) remains unknown. Method We collected clinical records from 79 COVID-19 patients at Wuhan Union hospital (China). Spearman’s correlation analysis, receiver operating characteristic (ROC) curve and Kaplan–Meier survival curves were employed. Results Patients with elevated ferritin levels had a higher incidence of severity illness (50.0 vs 2.9%) and liver injury (52.3 vs 20.0%) when compared with patients with normal ferritin levels (p < 0.05). Ferritin could effectively identify the severity of illness (ROC area 0.873) and liver injury (ROC area 0.752). The elevated ferritin group showed longer viral clearance time (median 16 vs 6 days, p < 0.001) and in-hospital length (median 18 vs 10 days, p < 0.001). Conclusions It suggests that ferritin could act as an easy-to-use tool to identify liver injury and severity illness and predict the prognosis of COVID-19 patients. Intensive surveillance is necessary for patients with abnormal ferritin levels.

Diagnostic importance of hepcidin, soluble transferrin receptor (sTfR) and TfR-F index in monitoring the iron status of female hockey players

Latent iron deficiency is highly prevalent among female athletes compared to the sedentary population. The present study is designed to assess whether the subnormal ferritin levels observed in female hockey players were due to true iron deficiency or due to exercise-induced metabolic adaptations. Twenty-six female field hockey players were selected for this study, after assessing the iron profile parameters they were divided into two groups namely the low ferritin group (LFG) and normal ferritin group (NFG) based on their ferritin levels (cut-off value -12ng/ml). Hepcidin, soluble transferrin receptor (sTfR), soluble transferrin receptor-ferritin index (TfR-F Index), levels were compared between groups. Though there was no significant difference in TfR levels, significant differences were observed in hepcidin, TfR-F Index, serum iron, TIBC, and TS levels between both the groups, indicating the incidence of depletion of stored iron in female players during the training cycle.

Could Some Laboratory Parameters Predict Mortality in COVID-19?

The number of confirmed cases of COVID-19 continues to increase worldwide and threatens public health. Our aim in this study is to examine the relationship between some laboratory parameters and hematological ratios with the severity of the disease and hospital mortality. This study was designed as a retrospective cohort. The clinical data of 743 COVID-19 diagnosed patients who were eligible for hospitalization between March 16, and May 15, 2020 analyzed, retrospectively. The patients were separated into two groups as discharged from hospital (n = 681) and dead in hospital (n = 62). ROC curves and cutoff values of NLR (Neutrophil/Lymphocyte Ratio), PLR (Platelet/Lymphocyte Ratio), MLR (Monocyte/ Lymphocyte Ratio), CRP, and ferritin upon admission to hospital were calculated for the two groups. Binary Logistic Regression used to determine independent risk factors for mortality. The difference between both groups for age, duration in hospital, WBC, neutrophil, lymphocyte, NLR, PLR, MLR, CRP, and ferritin values were statistically significant. NLR had the highest area under the curve with a cutoff of 5.5 in the ROC curve [(AUC: 0.892, 95% CI: 0.844 - 0.939); Sensitivity = 85%, Specificity = 84%]. NLR, MLR, PLR, CRP and Ferritin groups have significant effects on the survival times of the Covid-19 patients. According to logistic regression analysis, increments of NLR (OR = 18.1, 95% CI: 6.4 - 51.4), CRP (OR = 5.5, 95% CI: 2.5 - 12.2), and age (OR = 2.7 95% CI: 1.3 - 5.5) values proportionally increase the death probability. NLR, CRP, and age are independent risk factors for mortality from COVID-19. We believe that evaluating these parameters together during diagnosis will be important in predicting the prognosis of the disease and in treatment approaches.

High Transfusion Dependence and Serum Ferritin but Not Transferrin Saturation Predict Inferior Clinical Outcomes in Patients with MDS

High Transfusion Dependence and Serum Ferritin but Not Transferrin Saturation Predict Inferior Clinical Outcomes in Patients with MDS

Magnetic resonance imaging accurately tracks kidney pathology and heterogeneity in the transition from acute kidney injury to chronic kidney disease

Acute kidney injury (AKI) increases the risk for chronic kidney disease (CKD). However, there are few tools to detect microstructural changes after AKI. Here, cationic ferritin-enhanced magnetic resonance imaging (CFE-MRI) was applied to examine the heterogeneity of kidney pathology in the transition from AKI to CKD. Adult male mice received folic acid followed by cationic ferritin and were euthanized at four days (AKI), four weeks (CKD-4) or 12 weeks (CKD-12). Kidneys were examined by histologic methods and CFE-MRI. In the CKD-4 and CKD-12 groups, glomerular number was reduced and atubular cortical lesions were observed. Apparent glomerular volume was larger in the AKI, CKD-4 and CKD-12 groups compared to controls. Glomerular hypertrophy occurred with ageing. Interglomerular distance and glomerular density were combined with other MRI metrics to distinguish the AKI and CKD groups from controls. Despite significant heterogeneity, the noninvasive (MRI-based) metrics were as accurate as invasive (histological) metrics at distinguishing AKI and CKD from controls. To assess the toxicity of cationic ferritin in a CKD model, CKD-4 mice received cationic ferritin and were examined one week later. The CKD-4 groups with and without cationic ferritin were similar, except the iron content of the kidney, liver, and spleen was greater in the CKD-4 plus cationic ferritin group. Thus, our study demonstrates the accuracy and safety of CFE-MRI to detect whole kidney pathology allowing for the development of novel biomarkers of kidney disease and providing a foundation for future invivo longitudinal studies in mouse models of AKI and CKD to track nephron fate.

MO015HAEMODIALYSIS VASCULAR ACCESS THROMBOSIS: AN ANALYSIS OF EVENTS FROM THE PROACTIVE IV IRON THERAPY IN HAEMODIALYSIS PATIENTS (PIVOTAL) TRIAL

Abstract Background and Aims Haemodialysis vascular access thrombosis (VAT) is a common occurrence that undermines the safe and effective delivery of haemodialysis (HD) and has been associated with anaemia therapy. In the Proactive IV Iron Therapy in Haemodialysis Patients trial (PIVOTAL), proactive high-dose intravenous iron dosing was compared with reactive low-dose intravenous iron dosing. VAT was a pre-specified secondary endpoint. Here we present data detailing the VAT events in PIVOTAL, alongside univariate and multivariate analyses of risk association, testing the hypothesis that VAT may be independently associated with a proactive iron dosing regimen. Method In PIVOTAL 2141 adults with end-stage kidney disease within 12 months of initiating regular HD were randomised 1:1 to either high-dose intravenous iron administered proactively, or low-dose intravenous iron administered reactively, on the basis of monthly Ferritin and Transferrin saturation levels. Erythropoiesis Stimulating Agents were dosed sufficiently to maintain a haemoglobin of 100 to 120g/L. Vascular access use was recorded at baseline and on a monthly basis. VAT was regarded as a safety event with investigators mandated to record such events. VAT was defined clinically, with investigators expected to report thrombotic occlusion of the access (either arteriovenous or catheter thrombosis) significant enough to prevent further effective use without intervention. Baseline demographic, blood pressure and laboratory data underwent univariate analysis with regard to first event of VAT. Primary patient demographics (age, gender, primary renal disease, randomised treatment arm) were put forward for inclusion in a multivariable cox proportional hazards model alongside variables that associated on univariate testing with α&amp;lt;0.05. Analyses were performed using SAS software, version 9.4 (SAS Institute). Results 2141 eligible patients were randomised, of whom 877/2141 (41.0%) were using a central venous catheter (CVC), 1209/2141 (56.5%) an arteriovenous fistula (AVF), and 55/2141 (2.6%) an arteriovenous graft (AVG) at baseline. Over a median follow up of 2.1 years, 480/2141 (22.4%) experienced a VAT event; 194/887 (21.9%) of CVC patients; 263/1209 (21.8%) of AVF patients; and 23/55 (41.8%) of AVG patients. On univariate testing VAT events associated with diabetes as a cause of kidney failure (HR 1.44, 95%CI 1.19 to 1.74, p&amp;lt;0.001), AVG use at baseline (HR 2.37, p&amp;lt;0.001), digoxin use (HR 2.35, p=0.002), and diuretic use (HR 1.24, p=0.02). Angiotensin receptor blocker (ARB) use associated with less VAT (HR 0.66, p=0.013), as did male gender (HR 0.74, p=0.002), and never having smoked (HR 0.68, p=0.008). No association was seen with age, AVF use, CVC use, blood pressure, history of cardiovascular (CV) disease, atrial fibrillation, other CV medications, C-reactive protein, haemoglobin, transferrin saturation, ferritin or randomised treatment group (Proactive 262/1093 (24.0%) v Reactive 218/1048 (20.8%), HR 1.15, p=0.12) . Multivariate analysis found diabetes as a cause of kidney failure (HR 1.45, p&amp;lt;0.001), AVG use (HR 2.29, p&amp;lt;0.001), digoxin exposure (HR 2.48, p&amp;lt;0.001) and diuretic exposure (HR 1.25, p=0.018) to independently associate with VAT. Male gender (HR 0.75, p=0.002), never smoked (HR 0.68, p=0.004) and ARB use (HR 0.66, p=0.011) were found to independently associate with lower risk of VAT. Investigation of interaction between significant predictors found diuretic use in AVF patients to reach nominal significance (p=0.033). No other significant interactions being demonstrated. Conclusion In PIVOTAL, VAT affected nearly one quarter of the cohort over a median of 2.1 years. Diabetes as a cause of kidney failure, active smoking, AVG use, female gender, exposure to digoxin, and exposure to diuretic were independently associated with VAT, but this was not the case with higher iron dosing. ARB use was independently associated with lower risk.

Phlebotomy requirements are lower in polycythemia vera patients with low ferritin stores.

e19537 Background: Polycythemia vera (PV) is a myeloid neoplasm of clonal red cell proliferation. Most PV patients are iron deficient at diagnosis, prior to the onset of therapeutic phlebotomy, the mainstay of treatment. More recent studies have also suggested that aberrant iron homeostasis contributes to persistently elevated hematocrit in iron deficient PV patients. In healthy individuals, iron deficiency leads to anemia such that the co-occurrence of polycythemia and iron deficiency in PV is pathological. The purpose of our study is to investigate whether iron deficiency, as defined by serum ferritin &lt; 15 μg/L, at PV diagnosis can predict phlebotomy requirements in PV patients. Methods: 173 patients were diagnosed with PV between 2010 and 2019 at our institution. We analyze ferritin levels, phlebotomy frequency, and cytoreductive therapy in PV patients. Patients are stratified into a “high ferritin” (serum ferritin &gt; 30 μg/L) or “low ferritin” (serum ferritin &lt; 15 μg/L) groups and analyzed at 0-6 months and 4-6 years after diagnosis. 91% of PV patients were treated with phlebotomy and 70% with cytoreductive therapy. 23 and 13 patients had both a ferritin level and a record of the number of phlebotomies at 0-6 months or 4-6 years after diagnosis, respectively. Results: The average number of phlebotomies at 0-6 months after diagnosis was 3.1±1.7, with no statistically significant difference between the low and high ferritin groups. The average number of phlebotomies at 4-6 years after diagnosis was 2.9±2.5, with no statistically significant difference between the low and high ferritin groups (1.9 vs. 4.6 phlebotomies, respectively; p = 0.136). In patients with low ferritin at diagnosis, phlebotomy requirements decreased at 4-6 years relative to 0-6 months after diagnosis (1.9 vs. 3.1 phlebotomies; p = 0.009) while no difference occurred in the high ferritin group. In all PV patients, average serum ferritin increased with time from diagnosis (R = 0.81) and cannot be explained by cytoreductive therapy as there was no significant effect on average ferritin levels (137 vs. 60 μg/L; p = 0.295) or phlebotomy requirements (3.2 vs. 3.4; p = 0.803) at 4-6 years after PV diagnosis. Conclusions: Low ferritin levels at PV diagnosis decreased phlebotomy frequency at 4-6 years relative to 0-6 months after diagnosis. Additionally, cytoreductive therapy did not significantly affect phlebotomy requirements or ferritin levels at 4-6 years post-PV diagnosis. Further work is needed to assess the molecular pathways involved in iron-deficient erythrocytosis in PV.

Retrospective Evaluation of Relationship Between Iron Overload and Transplantation Complications in Pediatric Patient Who Underwent Allogeneic Stem Cell Transplantation Due to Acute Leukemia and Myelodysplastic Syndrome.

Hematopoietic stem cell transplantation (HSCT) is a curative therapy option for hematologic malignancies. Iron overload is common in this patient group and can impact short-term and long-term nonrelapse mortality. Retrospective observational cohort study. To evaluate the effect of iron load on early and late HSCT outcomes in patients with acute leukemia and myelodysplasia to assess the necessity of reducing iron load. Sixty patients who underwent HSCT in pediatric stem cell transplantation unit between 2000 and 2012 were evaluated retrospectively. The patients were divided into those with pretransplantation serum ferritin levels above and below the median value of 1299 ng/mL. Forty-two (70%) of the patients were male, mean ages of the low and high ferritin groups were 85.43±9.42 and 118.56±10.04 months, respectively. Acute graft-versus-host disease (GVHD) within the first 100 days and acute liver GVHD were significantly more common in the high ferritin group (P<0.011 for both). Ferritin level was not associated with rates of engraftment syndrome, veno-occlusive disease, early/late infection, relapse, or overall and disease-free survival. In our study, significant result especially in terms of acute liver GVHD, was important to emphasize the need to be more careful in terms of acute liver GVHD risk in early liver pathologies in patients with high levels of ferritin after transplantation. In future large studies may be helpful to explain the relationship between acute liver GVHD and high ferritin levels.

Association of Serum Ferritin Levels Before Start of Conditioning With Mortality After alloSCT - A Prospective, Non-interventional Study of the EBMT Transplant Complications Working Party.

Elevated serum ferritin levels occur due to iron overload or during inflammation and macrophage activation. A correlation of high serum ferritin levels with increased mortality after alloSCT has been suggested by several retrospective analyses as well as by two smaller prospective studies. This prospective multicentric study aimed to study the association of ferritin serum levels before start of conditioning with alloSCT outcome. Patients with acute leukemia, lymphoma or MDS receiving a matched sibling alloSCT for the first time were considered for inclusion, regardless of conditioning. A comparison of outcomes between patients with high and low ferritin level was performed using univariate analysis and multivariate analysis using cause-specific Cox model. Twenty centers reported data on 298 alloSCT recipients. The ferritin cut off point was determined at 1500 μg/l (median of measured ferritin levels). In alloSCT recipients with ferritin levels above cut off measured before the start of conditioning, overall survival (HR = 2.5, CI = 1.5–4.1, p = 0.0005) and progression-free survival (HR = 2.4, CI = 1.6–3.8, p < 0.0001) were inferior. Excess mortality in the high ferritin group was due to both higher relapse incidence (HR = 2.2, CI = 1.2–3.8, p = 0.007) and increased non-relapse mortality (NRM) (HR = 3.1, CI = 1.5–6.4, p = 0.002). NRM was driven by significantly higher infection-related mortality in the high ferritin group (HR = 3.9, CI = 1.6–9.7, p = 0.003). Acute and chronic GVHD incidence or severity were not associated to serum ferritin levels. We conclude that ferritin levels can serve as routine laboratory biomarker for mortality risk assessment before alloSCT.

Association between Serum Ferritin and Blood Lipids: Influence of Diabetes and hs-CRP Levels.

This study is aimed at exploring the relationship between serum ferritin and blood lipids and the influence of diabetes and different hs-CRP levels. A total of 8163 subjects were analyzed. Participators were classified according to serum ferritin, diabetes, and two hs-CRP levels. Blood lipids were determined using standardized methods and conditions. Except for HDL-C, there was a significant increase in blood lipids in the progressive ferritin group with normal hs-CRP levels (P < 0.05). But HDL-C was just the opposite (P < 0.0001). In nondiabetic patients, TG, TC, and LDL-C were significantly elevated in the progressive ferritin group (P < 0.05). And, HDL-C was just the opposite (P < 0.05). The generalized linear model and the parsimonious model showed that serum TG was positively correlated with ferritin, and LDL-C was negatively correlated with ferritin (P < 0.05). But the correlation between LDL-C and ferritin was broken (P > 0.05). After a sufficient adjustment, there was a positive correlation between serum TG and ferritin and a negative correlation between LDL-C and ferritin. Nonetheless, a negative correlation between LDL-C and ferritin is influenced by diabetes frailly. And, there was no change of relationship between lipids and ferritin in different hs-CRP levels. We found a real relationship between ferritin and lipids after sufficient adjustment for confounders.

Effect of Maintenance Intravenous Iron Treatment on Erythropoietin Dose in Chronic Hemodialysis Patients: A Multicenter Randomized Controlled Trial.

Background:There is no consensus on intravenous (IV) iron supplement dose, schedule, and serum ferritin target in functional iron deficiency anemia to maintain optimum target levels of iron stores by several guidelines.Objective:To examine the effect of IV iron supplementation to different targets of serum ferritin on erythropoietin dose and inflammatory markers in chronic hemodialysis (HD) patients with functional iron deficiency anemia.Design:A multicenter, randomized, open-label study.Setting:In a developing country, Thailand.Patients:Chronic HD patients with functional iron deficiency anemia.Measurements:Erythropoietin resistance index, high-sensitivity C-reactive protein, and fibroblast growth factor 23.Methods:Two hundred adult chronic HD patients with transferrin saturation less than 30% and serum ferritin of 200 to 400 ng/mL were randomized 1:1 to maintain serum ferritin 200 to 400 ng/mL (low-serum ferritin group, N = 100) or 600 to 700 ng/mL (high-serum ferritin group, N = 100). During a 6-week titration period, participants randomized to the high-serum ferritin group initially received 600 mg IV iron (100 mg every week), while the participants in the low-serum ferritin group did not receive IV iron. During the 6-month follow-up period, the dose of IV iron was adjusted by protocol.Results:The mean dose of IV iron was 108.3 ± 28.2 mg/month in the low-serum ferritin group and 192.3 ± 36.2 mg/month in the high-serum ferritin group. The mean serum ferritin was 367.0 ± 224.9 ng/mL in the low ferritin group and 619.6 ± 265.2 ng/mL in the high ferritin group. The erythropoietin resistance index was significantly decreased in the high-serum ferritin group compared to the low-serum ferritin group after receiving IV iron in the 6-week titration period (mean difference: −113.43 ± 189.14 vs 41.08 ± 207.38 unit/week/g/dL; P < .001) and 3-month follow-up period (mean differences: −88.88 ± 234.43 vs −10.48 ± 217.75 unit/week/g/dL; P = .02).Limitations:Short follow-up period.Conclusion:Maintaining a serum ferritin level of 600 to 700 ng/mL by IV iron administration of approximately 200 mg per month as a maintenance protocol can decrease erythropoietin dose requirements in chronic HD patients with functional iron deficiency anemia.Trials registration:The study was registered with the Thai Clinical Trials Registry TCTR20180903003.

The Effect of Serum Ferritin Level on Gonadal, Prolactin, Thyroid Hormones, and Thyroid Stimulating Hormone in Adult Males with Sickle Cell Anemia.

BackgroundSickle cell anaemia (SCA) is an inherited hemoglobinopathy resulting in sickling of erythrocytes that cause micro-vascular obstruction leading to acute complications and chronic organ damage. Adults with SCA have endocrine complications and metabolic alterations. The aim of this study was to assess the association between gonadal and thyroid hormones with iron indices and to explore the potential association between serum ferritin levels and sex hormones in adult males with sickle cell disease in New Prince Saud Bin Jalawy Hospital (NPSBJH) in Hofuf city (Eastern region of Saudi Arabia) where there are many patients with SCA.MethodsA cross-sectional analytical study was carried out in the Haematology Clinic at NPSBJH in 2018. A total of eighty (80) male patients with sickle cell anaemia were included in this study and were divided into two groups according to serum ferritin level. Group I (G-I): Included 40 male patients with high serum ferritin level and group II (G-II): included 40 male patients with normal serum ferritin level.ResultsThere was a significant difference in height/cm between GI and Gil, P value= 0.006. Serum ferritin was significantly higher in GI (P value= 0.000), and serum TIBC was significantly higher in G-II. (P value= 0.022). Testosterone level was significantly higher in G-II (P value= 0.018). Luteinizing hormone (LH) was significantly higher in group I (P-value 0.019). There was a significant relation between serum ferritin level in G-I and the following: serum iron, TIBC, serum testosterone, LH, prolactin, free T3 and free T4.ConclusionAdult males with SCD with high serum ferritin level were shorter than adult males with SCD who had normal serum ferritin level and had a significant lower level of serum testosterone and significant high level of LH and this was most likely due to endocrine dysfunction secondary to high ferritin level and iron overload.