High Ferritin Group Research Articles

The Effect of Ferritin Level on Respiratory Functions in Patients with β-Thalassemia Major

Introduction-Purpose β-thalassemia major (β-TM) is an autosomal recessive disorder caused by mutations in the β-globin gene of hemoglobin. The disease is characterized by splenomegaly due to ineffective erythropoiesis, iron accumulation signs in tissues as a result of increased iron absorption, bone expansion due to increased erythropoietic activity, and decreased tissue oxygenation. One of the effected organ can be the lungs due to excessive iron deposition in these patients. The current study aimed to investigate the effect of serum ferritin level, which is known as a marker of iron accumulation in tissues, on pulmonary function tests (PFT) in patients with β-TM. Methods and Materials Patients aged ≥6 years who were regularly followed in the pediatric hematology section of Mersin City Research and Training Hospital with a diagnosis of β-TM were included. All patients received regular blood transfusion and iron chelation therapy. Study participants underwent PFT prior to blood transfusion in the pediatric pulmonology section Results A total of 43 patients with β-TM were studied. Included patients were divided into two groups according to the mean annual ferritin level; low ferritin group if below 2000 ml/ng and high ferritin group if above 2000 ml/ng. The low ferritin group was consisted of 19 patients and the high ferritin group was consisted of 24 patients. The characteristics of these two groups are shown in Table 1. There were no statistical significance in age, gender, body mass index, age at diagnosis, mean annual hemoglobin, splenectomy, cardiac involvement and oxygen saturation among both groups, but the number of annual transfusion was significantly higher in the high ferritin group than lower ferritin group. When PFT parameters of both groups were compared, FVC (forced vital capacity) was statistically lower in the high ferritin group compared to the low ferritin group. Other parameters included FEV 1 (forced expiratory volume in 1 second), FEV 1/FVC ratio, PEF (peak expiratory flow) and FEF 25-75 (forced expiratory flow between 25% and 75% of vital capacity) were similar among groups. (Table 2) Discussion Patients with β-TM may accumulate iron in the interstitial area of the lungs which can lead fibrosis and impaired lung function over time. There are several studies investigated lung dysfunction and its etiology in these patients. Although the results of the studies are varied, the majority of them reported a restrictive pattern of respiratory dysfunction in thalassemia patients. Additionally, some studies showed the presence of mild or moderate obstruction in small airways and decrease in diffusion capacity with the increase of alveolar-capillary membrane thickness at advanced ages. In the present study, we found that patients with β-TM who had high ferritin level showed restrictive type lung function compared to those with low ferritin level. There were no difference among the groups in obstructive parameters (i.e. FEV 1, FEV 1/FVC, FEF 25-75) of PFT. In the literature, studies investigating PFT in patients with high ferritin levels had variable results, impaired or no change, in pulmonary status. In conclusion, loss of respiratory function and impaired tissue oxygenation in patients with β-TM may develop over time due to iron deposition in the interstitial area. PFT assessment of these patients is essential and recommended for the detection of early lung disease. Routine PFT follow in patients with β-TM of high ferritin values is highly important.

Association between Serum Ferritin and Prognosis in Patients with Ischemic Heart Disease in Intensive Care Units.

Recent years have seen a clear link established between elevated ferritin levels and COVID-19 prognosis. However, the impact of heightened ferritin levels on the prognosis of individuals with severe ischemic heart disease remains uncertain. We utilized the MIMIC IV database to identify a cohort of ischemic heart disease patients who underwent serum ferritin testing. We conducted regression analyses, employed the overlap propensity score weighting model, and utilized the restricted cubic splines model to comprehensively investigate the associations between serum ferritin levels and clinical outcomes. Our cohort included 1173 patients with diagnosed ischemic heart disease, categorized into high and low serum ferritin groups. After meticulous adjustment for confounding factors in a fully adjusted model, the hazard ratios (HRs) for 90-day and 1-year mortality were 1.63 (95% CI: 1.27-2.09) and 1.49 (95% CI: 1.19-1.86), respectively, in the high-ferritin group compared to the low-ferritin group. Subsequent analyses with propensity score weighting confirmed these results. Remarkably, restricted cubic spline analysis revealed an almost linear relationship between log-transformed serum ferritin levels and the risk of both 90-day and 1-year all-cause mortality. Moreover, incorporating ferritin into conventional severity of illness scores significantly improved the area under the curve for both 90-day and 1-year mortality. This study provides compelling evidence regarding the prognostic significance of serum ferritin in predicting 90-day and one-year mortality rates among patients diagnosed with ischemic heart disease.

Prognostic Value of Serum Ferritin for Patients with Severe Fever with Thrombocytopenia Syndrome: A Single-Center Retrospective Cohort Study.

This article aims to evaluate the prognostic value of ferritin in patients with severe fever with thrombocytopenia syndrome (SFTS). Patients with SFTS diagnosed at the Infection Department of Wuhan Union Medical College Hospital from July 2018 to November 2021 were included. The best cutoff value was determined by receiver-operating characteristic (ROC) curve. The survival curve was analyzed by Kaplan-Meier method and compared among different serum ferritin subgroups by log-rank test. Cox regression model was used to evaluate the effect of prognosis on overall survival (OS). A total of 229 patients with febrile thrombocytopenia syndrome were enrolled. There were 42 fatal cases, with a fatality rate of 18.3%. The best critical value of serum ferritin was 16.775mg/l. With increasing serum ferritin level, the cumulative mortality increased significantly (log-rank, P < 0.001). Cox univariate regression analysis and adjusted confounding factors such as age, viral load, liver and kidney function and blood coagulation function showed that, compared with the low ferritin group, the high ferritin group demonstrated poorer OS. The serum ferritin level before treatment can be considered a valuable index for predicting the prognosis of patients with SFTS.

Electrophysiological properties and heart rate variability of patients with thalassemia major in Jakarta, Indonesia.

Beta thalassemia major (TM) is a common hereditary disease in Indonesia. Iron overload due to regular transfusion may induce myocardial iron deposition leading to electrophysiological dysfunction and functional disorders of the heart. Ventricular arrhythmia is one of the most common causes of sudden cardiac death in thalassemia patients. This cross-sectional study of 62 TM patients aged 10-32 years in Cipto Mangunkusumo General Hospital was done to assess their electrophysiological properties and heart rate variability, including 24- hour Holter monitoring, signal averaged electrocardiogram (SAECG) for detection of ventricular late potential (VLP), and determination of heart rate variability (HRV). We also assessed their 12-lead ECG parameters, such as P wave, QRS complex, QT/ QTc interval, QRS dispersion, and QT/ QTc dispersion. Iron overload was defined by T2-star magnetic resonance (MR-T2*) values of less than 20 ms or ferritin level greater than 2500 ng/mL. Subjects were grouped accordingly. There were significant differences of QTc dispersion (p = 0.026) and deceleration capacity (p = 0.007) between MR-T2* groups. Multivariate analysis showed an inverse correlation between QTc dispersion and MR-T2* values. There was a proportional correlation between heart rate deceleration capacity in the low MR-T2* group (p = 0.058) and the high ferritin group (p = 0.007). No VLPs were detectable in any patients. In conclusion, prolonged QTc dispersion and decreased heart rate deceleration capacity were significantly correlated with greater odds of iron overload among patients with Thalassemia major.

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.

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.

Increased levels of ferritin on admission predicts intensive care unit mortality in patients with COVID-19

BackgroundThe aim of this study was to evaluate hyperferritinemia could be a predicting factor of mortality in hospitalized patients with coronavirus disease-2019 (COVID-19). MethodsA total of 100 hospitalized patients with COVID-19 in intensive care unit (ICU) were enrolled and classified into moderate (n=17), severe (n=40) and critical groups (n=43). Clinical information and laboratory results were collected and the concentrations of ferritin were compared among different groups. The association between ferritin and mortality was evaluated by logistic regression analysis. Moreover, the efficiency of the predicting value was assessed using receiver operating characteristic (ROC) curve. ResultsThe amount of ferritin was significantly higher in critical group compared with moderate and severe groups. The median of ferritin concentration was about three times higher in death group than survival group (1722.25μg/L vs. 501.90μg/L, p<0.01). The concentration of ferritin was positively correlated with other inflammatory cytokines, such as interleukin (IL)-8, IL-10, C-reactive protein (CRP) and tumor necrosis factor (TNF)-α. Logistic regression analysis demonstrated that ferritin was an independent predictor of in-hospital mortality. Especially, high-ferritin group was associated with higher incidence of mortality, with adjusted odds ratio of 104.97 [95% confidence interval (CI) 2.63–4185.89; p=0.013]. Moreover, ferritin had an advantage of discriminative capacity with the area under ROC (AUC) of 0.822 (95% CI 0.737–0.907) higher than procalcitonin and CRP. ConclusionThe ferritin measured at admission may serve as an independent factor for predicting in-hospital mortality in patients with COVID-19 in ICU.

Increased levels of ferritin on admission predicts intensive care unit mortality in patients with COVID-19

BackgroundThe aim of this study was to evaluate hyperferritinemia could be a predicting factor of mortality in hospitalized patients with coronavirus disease-2019 (COVID-19). MethodsA total of 100 hospitalized patients with COVID-19 in intensive care unit (ICU) were enrolled and classified into moderate (n=17), severe (n=40) and critical groups (n=43). Clinical information and laboratory results were collected and the concentrations of ferritin were compared among different groups. The association between ferritin and mortality was evaluated by logistic regression analysis. Moreover, the efficiency of the predicting value was assessed using receiver operating characteristic (ROC) curve. ResultsThe amount of ferritin was significantly higher in critical group compared with moderate and severe groups. The median of ferritin concentration was about three times higher in death group than survival group (1722.25μg/L vs. 501.90μg/L, p<0.01). The concentration of ferritin was positively correlated with other inflammatory cytokines, such as interleukin (IL)-8, IL-10, C-reactive protein (CRP) and tumor necrosis factor (TNF)-α. Logistic regression analysis demonstrated that ferritin was an independent predictor of in-hospital mortality. Especially, high-ferritin group was associated with higher incidence of mortality, with adjusted odds ratio of 104.97 [95% confidence interval (CI) 2.63–4185.89; p=0.013]. Moreover, ferritin had an advantage of discriminative capacity with the area under ROC (AUC) of 0.822 (95% CI 0.737–0.907) higher than procalcitonin and CRP. ConclusionThe ferritin measured at admission may serve as an independent factor for predicting in-hospital mortality in patients with COVID-19 in ICU.

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.

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.

Serum ferritin levels at diagnosis predict prognosis in patients with low blast count myelodysplastic syndromes.

Serum ferritin, a marker of systemic iron status, is considered a prognostic factor for patients with myelodysplastic syndromes (MDS), despite the lack of supporting evidence. We investigated the association between serum ferritin levels at diagnosis and the prognoses of Japanese MDS patients with bone marrow blasts < 5% and peripheral blood blasts < 2%. Three hundred and ninety patients with cytopenia were registered prospectively in the multicenter database, among whom 107 patients with MDS (72 males and 35 females, with a median age of 70years) met the eligibility criteria. The median serum ferritin level at diagnosis was 204ng/mL; we divided the cohort into low (n = 56) and high (n = 51) ferritin groups using a cutoff of 210ng/mL. Kaplan-Meier analyses revealed that the 3-year overall survival (OS) of the high ferritin group was significantly shorter than that of the low ferritin group (66% and 79%, respectively). The cumulative incidences of leukemic progression were similar between the groups. On multivariate analysis, age, blast percentage, cytogenetic abnormalities, and serum ferritin levels at diagnosis were independently associated with OS in our patients. Thus, modest elevations of ferritin levels at diagnosis may influence the prognoses of patients with MDS who have low blast counts.

Association between serum ferritin levels and clinical outcomes in maintenance hemodialysis patients: a retrospective single-center cohort study

BackgroundFerritin is a well-known marker of iron deficiency anemia, but the target in maintenance hemodialysis (MHD) patients remains controversial. This study examined the association between baseline ferritin levels and clinical outcomes.MethodsWe retrospectively collected the data of outpatients on MHD for 5 years at St. Luke’s International Hospital from July 2009. Patients with baseline ferritin levels of > 100 ng/mL in June 2009 were defined as the high-ferritin (HF) group and the remaining patients as the low-ferritin (LF) group. The primary endpoint was all-cause mortality. The secondary endpoints included cardiovascular events and infection-related hospitalizations. Log-rank test and Cox proportional hazard analysis were performed.ResultsOf 116 patients (age, 65.4 ± 13.4 years, 70% males), 29 (25%) and 87 (75%) belonged to the HF and LF groups, respectively. During the follow-up period of 1825 (interquartile range 819–1825) days, 38 patients (23 in the HF and 15 in the LF groups) died. According to the Kaplan–Meier survival curves, the HF group had significantly poor survival compared with the LF group (p = 0.0089). After adjusting for age, sex, vintage of hemodialysis, C-reactive protein levels, and history of cardiovascular events, the hazard ratio (HR) for the HF group was 2.49 (95% confidence interval (CI), 1.21–5.12). The multivariate analysis of cardiovascular events revealed a similar result with statistical significance (HR 2.69; 95% CI 1.12–6.46). Infection-related hospitalizations did not exhibit any statistically significant difference.ConclusionsIn MHD patients, ferritin levels > 100 ng/mL is associated with increased rates of all-cause mortality and cardiovascular events.

Clinical Significance of Serum Ferritin at Diagnosis in Patients With Acute Myeloid Leukemia: A YACHT Multicenter Retrospective Study

PurposeA multicenter retrospective analysis was performed to evaluate the clinical significance of serum ferritin at diagnosis in patients with acute myeloid leukemia (AML). MethodsThe study cohort included 305 patients who were newly diagnosed with AML from 2000 to 2015 and received standard induction chemotherapy. Transplantation was performed in 168 patients. ResultsThe median ferritin value was 512 ng/mL (range, 8-9475 ng/mL). Ferritin correlated with lactate dehydrogenase, C-reactive protein, white blood cell count, and blast count, and elevation of ferritin was associated with poor performance status. The median follow-up period was 58 months (range, 4-187 months) among survivors. The high ferritin group (≥ 400 ng/mL) demonstrated inferior event-free survival (EFS) at the 5-year interval (30% vs. 40%; P = .033) compared to the low ferritin group. Multivariate analysis in the high-risk karyotype revealed that high ferritin levels predicted worse EFS (hazard ratio = 2.07; 95% confidence interval, 1.28-3.33; P = .003). ConclusionElevated ferritin at diagnosis may indicate tumor burden in patients with AML and predict worse EFS in the high-risk group.

A Study on Cardiopulmonary Function Tests in Thalassemia Major Patients (6-14 Years) and its Correlation to Serum Ferritin

Background: Patients with thalassemia major require regular blood transfusions which causes iron overload which untreated leads to respiratory, cardiac, hepatic and endocrine dysfunction. Objectives: This study was undertaken to assess cardiopulmonary functions in thalassemia major patients and its correlation to serum ferritin. Methods: A hospital based observational study was conducted over a period of 11 months, between November 2015 and September 2016. 47 thalassemia major patients were included along with 20 age and sex matched controls were taken as controls. Results: Mean age in our study population was 9.44 ± 2.030 years. The mean Sr. ferritin level was 3217+1351.853 ng/dl. 18 (38%) patients had low FEV1 and FVC; suggesting restrictive pattern along with small airway obstruction suggested by reduced FEF25% to 75%. We observed that as the serum ferritin level increased, mean value of FEV1, FVC, FEV1/FVC, FEF (25% to 75%) decreased and it was statistically significant in cases with ferritin >3000 ng/ml (p value 3000 ng/dl and 5 patients out of 17 (31%) had dilated cardiomypathy in ferritin levels of 2000 to 3000 ng/dl. So the cardiovascular complications were found to be higher in the high-ferritin group (serum ferritin>3000 ng/dl) than in low-ferritin group (serum ferritin 1000-2000). In our study among 47 Thalassemic patients, 15 (40%) were found to have both cardiac pathology as well as pulmonary dysfunction. This finding was statistically significant. Conclusion: At the end of our study on thalassemic patients, we concluded that all the PFT parameters were decreased with increasing Sr. ferritin level. Most of the echocardiographic parameters were found to be significantly deranged with reference to increase in Sr. ferritin levels. Nearly half of the patients were found to have both pulmonary and cardiac involvement.

Serum ferritin is a different predictor from transfusion history for allogeneic transplantation outcome in patients with severe aplastic anemia

ABSTRACTObjectives: Severe aplastic anemia (SAA) patients receive more red blood cell (RBC) transfusions as supportive management. We aim to clarify the associations between transfusion history or pre-transplantation serum ferritin (SF) and the overall survival of allogeneic hematopoietic stem cell transplantation (allo-HSCT) among SAA patients.Material and methods: We retrospectively investigated 96 SAA patients undergoing allo-HSCT, and grouped them according to pre-transplantation duration. Pre-transplantation SF, transfused units and other iron-related parameters were collected. Comparisons in transplantation outcomes and complications were made in groups with different SF levels and different transfusion histories.Results: Among the 96 SAA patients, 45 patients received transplantation within 2 months after diagnosis (short-term pre-transplantation period), and the rest of the patients had long-term pre-transplantation treatment. Among the patients with short-term pre-transplantation treatment, a higher risk of death was seen in the high-ferritin group (p < 0.05). Elevated SF also predicted a trend in incidence of higher bloodstream infection (p = 0.108). Significant correlations were observed between pre-transplantation SF and infection incidence, as well as transfusion history. However, for patients with longer pre-transplantation duration, transfusion history was associated with worse outcome (p = 0.026), in terms of higher incidence of acute graft versus host disease (p = 0.048). High SF was only significantly associated with prolonged RBC transfusion dependence post-transplantation (p = 0.044).Discussion and conclusions: Transfusion history was a stronger predictor of outcome than SF in patients undergoing transplantation more than 2 months after diagnosis.