Ferritin Ratio Research Articles

The level of lactate dehydrogenase and ferritin in the blood of Covid-19 patients compared to healthy people in Iraq

60 samples were collected, 40 samples were for patients with CO-19 and 20 samples were for healthy control people. Tests were performed to know the patients people through the ADVIA Chemistry XPT System and an analysis was performed to find out the ratio of ferritin to patients based on I CHORMA. As for the LDH analysis, use the Cedex Bio Analyzer to find results were found that showed the great effect on ferritin and LDH, where the ratio of standard deviation to LDH to patients people was 441.5641 ± 234.80 and for control 185.08 ± 35.26 as for the analysis of ferritin, where the ratio of standard deviation was 853.92 ± 516.13 to patients people and for control 88.48 ± 59.44 And through the work of statistical analysis to know the effect of the CO-19 on the abnormal ratio, as the statistical analysis proved that there is a positive effect on ferritin and LDH to patients people and the control has a negative effect, and this explains the reason for the lack of the amount of iron present in the body is little if the person is a carrier of the disease

Clinical features and blood iron metabolism markers in children with beta-propeller protein associated neurodegeneration.

Neurodegeneration with brain iron accumulation constitutes a group of rare progressive movement disorders sharing intellectual disability and neuroimaging findings as common denominators. Beta-propeller protein-associated neurodegeneration (BPAN) represents approximately 7% of the cases, and its first signs are typically epilepsy and developmental delay. We aimed to describe in detail the phenotype of BPAN with a special focus on iron metabolism. We present a cohort of paediatric patients with pathogenic variants of WD-Repeat Domain 45 gene (WDR45). The diagnosis was established by targeted panel sequencing of genes associated with epileptic encephalopathies (n=9) or by Sanger sequencing of WDR45 (n=1). Data on clinical characteristics, molecular-genetic findings and other performed investigations were gathered from all participating centres. Markers of iron metabolism were analysed in 6 patients. Ten children (3 males, 7 females, median age 8.4 years) from five centres (Prague, Berlin, Vogtareuth, Tubingen and Cologne) were enrolled in the study. All patients manifested first symptoms (e.g. epilepsy, developmental delay) between 2 and 31 months (median 16 months). Seven patients were seizure-free (6 on antiepileptic medication, one drug-free) at the time of data collection. Neurological findings were non-specific with deep tendon hyperreflexia (n=4) and orofacial dystonia (n=3) being the most common. Soluble transferrin receptor/log ferritin ratio was elevated in 5/6 examined subjects; other parameters of iron metabolism were normal. Severity of epilepsy often gradually decreases in BPAN patients. Elevation of soluble transferrin receptor/log ferritin ratio could be another biochemical marker of the disease and should be explored by further studies.

Elevated serum levels of checkpoint molecules in patients with adult Still\u2019s disease

BackgroundThe interaction between galectin-9 (Gal-9) and its ligand, T cell immunoglobulin, and mucin-containing-molecule-3 (TIM-3), one of the coinhibitory receptors, transduce the inhibitory signaling to regulate immune responses. The dysregulated expression of checkpoint molecules has been reported under various inflammatory or autoimmune conditions. The aim of this study is to investigate the levels of these checkpoint molecules and their associations between proinflammatory markers in patients with adult Still’s disease (ASD).MethodsSerum samples were collected from 47 patients with active ASD, 116 patients with rheumatoid arthritis (RA), and 37 healthy controls (HCs). Serum levels of Gal-9, soluble TIM-3 (sTIM-3), and IL-18 were determined using enzyme-linked immunosorbent assay (ELISA). Results were compared with the clinical features of ASD.ResultsSerum Gal-9 levels in patients with ASD (median: 21.57 ng/ml, interquartile range IQR [11.41–39.72]) were significantly higher compared to those in patients with RA (7.58 ng/ml, IQR [5.57–10.20] p < 0.001) as well as those in HCs (4.51 ng/ml, [IQR; 3.58–5.45], p < 0.001). Similarly, serum sTIM-3 levels in patients with ASD were significantly higher than those in patients with RA and HCs. Serum levels of Gal-9 or sTIM-3 showed positive correlations with IL-18 levels (Gal-9; r = 0.90, p < 0.001, sTIM-3; r = 0.78, p < 0.001) in patients with ASD. Serum levels of Gal-9 or sTIM-3 correlated with serum ferritin (Gal-9; r = 0.77, p < 0.001, sTIM-3; r = 0.71, p < 0.001) and ASD disease activity score (Pouchot’s score, Gal-9; r = 0.66, p < 0.001, sTIM-3; r = 0.59, p < 0.001), whereas there was no significant correlation between serum Gal-9 or sTIM-3 and CRP. ASD patients with chronic arthritis phenotype had a significantly higher Gal-9/ferritin and sTIM-3/ferritin ratio than those without this phenotype. After immunosuppressive treatment, Gal-9 and sTIM-3 levels showed a significant decline in parallel to the disease activity scores.ConclusionsSerum levels of the coinhibitory checkpoint molecules were elevated and correlated with disease activity in patients with ASD. These coinhibitory checkpoint molecules may be implicated in the autoinflammatory process seen in ASD.

Iron Status from Early Through Late Pregnancy and Neonatal Anthropometric Measures: Friend or Foe?

Abstract Objectives Although iron status in pregnancy is an important factor for fetal growth, associations between maternal iron status and neonatal size are highly conflicting. Further, studies with longitudinal measures of iron status in pregnancy are scarce. This study investigated maternal iron status from early through late pregnancy using comprehensive measures of iron biomarkers (ferritin, hepcidin, soluble transferrin receptor [sTfR], and sTfR: ferritin ratio) in relation to neonatal size. Methods This study included 321 pregnant women without major chronic conditions before pregnancy who were enrolled in the NICHD Fetal Growth Study- Singletons (n = 2802). Plasma iron biomarkers (i.e., ferritin, sTfR, hepcidin) were measured at 4 visits (10–14, 15–26, 23–31, and 33–39 gestational weeks [GW]). We used linear and Poisson regression models adjusted for covariates including pre-pregnancy BMI and C-reactive protein to estimate the association of tertiles (T) of iron biomarkers and clinically defined iron status with neonatal anthropometry, such as birthweight (BW), risk of large and small-for-gestational age (LGA, SGA) and macrosomia. Results Iron deficiency (i.e., ferritin &amp;lt;12 ug/L) at 10–14 GW was related to increased risk of macrosomia and LGA; adjusted RR (95% confidence interval (CI)) were 3.64 (1.45, 9.17), and 14.2 (5.49, 36.4), respectively. At 15–26 GW, iron deficiency was also related to increased risk of LGA with a RR of 3.58 (1.13, 11.4). In contrast, at 33–39 GW, iron deficiency was related to lower risk of macrosomia with a RR of 0.06 (0.01, 0.36). The CIs were wide, largely due to small sample size of macrosomia cases. In addition, at 10–14 GW, lower iron status (indicated by higher sTfR levels) was related to greater BW; highest vs. lowest T mean BW was 3385 g vs. 3251 g with an adjusted p-value for difference &amp;lt;0.05. Conclusions Our findings among U.S. pregnant women without major chronic conditions before pregnancy suggest that the relation of maternal iron status to neonatal size may vary by gestational age and lower iron status in early pregnancy is generally related to heavier neonates. Funding Sources Intramural Research Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)/National Institutes of Health (NIH).

Use of the esa resistance index to guide dosing for anaemia management.

Identifying erythropoiesis-stimulating agent (ESA) resistance is important for treating reversible causes, reaching target haemoglobin levels with minimal dosing, avoiding adverse effects and reducing costs. The resistance index (RI, dose/kg weight/g haemoglobin/dl) is reportedly superior to absolute or weight-based dosing. With the growing number of ESA classes and medications, our goal was to develop methodology to establish RI ranges in otherwise healthy haemodialysis patients as a structured approach to identify remediable causes of anaemia. We retrospectively studied anaemia management with darbepoetin in 100 chronic haemodialysis patients and a subgroup of 48 without identifiable conditions that impair erythropoiesis. Data included inflammatory and bone marrow conditions, medications with hematologic effects, catheter use, iron, parathyroid and dialysis measures. The haematologically healthy group was aged 57.1 ± 1.9 SEM years, 33% diabetic, with haemoglobin 10.4 ± 0.2 g/dl. The darbepoetin RI (DRI) values were 0.05 ± 0.01, absolute dose 38.5 ± 3.5 mcg/week and weight-based 0.50 ± 0.05 mcg/kg. Regression analyses included iron saturation, ferritin, parathyroid hormone and urea reduction ratio. DRI was superior to other dosing approaches based on the distribution of results (kurtosis) and discordance between the measures that occurred in 17% of patients at haemoglobin target. We demonstrate the value of determining the RI for use with expanding ESA choices, using as an example how DRI values can be established for healthy haemodialysis patients so as to guide dosing. When elevated, the RI can trigger evaluation for remediable factors causing hyporesponsiveness even when haemoglobin goals have been reached.

Evaluation of Ferritin and Transferrin Ratio as a Prognostic Marker for Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) has tripled in incidence over the past 20years and now ranks as the third leading cause of mortality attributed to cancer. Underlying pathophysiology is sustained hepatic inflammation which results in hepatocellular dysplasia and thus an environment prone to HCC. Considering the essential role of inflammation in the pathogenesis of HCC, we evaluated the prognostic utility of ferritin-transferrin ratio (FTR) in HCC. We retrospectively reviewed the electronic medical records of patients with HCC (diagnosed on radiographic criteria and/or biopsy) from 2000 through 2015. We collected data regarding the patient demographics, laboratory investigations at the time of HCC diagnosis and prior to the initiation of treatment. Overall survival was calculated from the time of diagnosis, cases were censored at the date of last follow-up, if date of death was not known. Kaplan-Meier curves were estimated to evaluate the prognostic significance of FTR. Receiver operating characteristics (ROC) curve was plotted for FTR to predict mortality and identify cut-off value by optimized Youden's index. Among the 176 patients identified by initial screening, 116 patients were eventually included for analysis. Overall median survival was 11.9months. FTR, of note, was significantly lower in alive (6.9, p < 0.001). In univariate analysis, alfa-fetoprotein (AFP), aspartate aminotransferase (AST), serum ferritin (SF), transferrin (TFS), and FTR were significantly associated with mortality. On multivariate analysis for mortality, FTR, AFP, and epidemiologic factors predictive of mortality including male gender and advanced HCC were significant. The ferritin-transferrin ratio (FTR), calculated at the time of HCC diagnosis could predict mortality in our cohort of patients. With an optimal cut-off of 7.7 for FTR were stratified into high- and low-risk groups. The hazard ratio between the two groups was 2.36 (p < 0.003). Future studies with longitudinal follow-up of FTR at intervals and important time points (e.g., perioperative) might provide more insights to its prognostic value.

Serum and salivary ferritin levels in iron-deficiency anemia − is there a difference?

Introduction Iron-deficiency anemia (IDA) is one of the most important nutritional deficiencies in Egypt. The assessment of serum ferritin has been the gold standard method in the detection of this disease However, this involves the drawing of venous blood, which is invasive and is sometimes physically and psychologically traumatic to the patients, and sometimes it is difficult to withdraw blood from hidden veins. This study was done to estimate and correlate serum ferritin levels and saliva ferritin levels of patients with IDA, thus assessing the effectiveness of saliva as an alternative noninvasive diagnostic tool. This study was done to estimate, compare, and correlate the ferritin levels in serum and saliva of patients with IDA, to determine whether saliva can be used as a predictive marker to monitor the iron levels in IDA. Patients and methods A total of 60 patients with IDA and 20 healthy participants as control were chosen for the study. Quantitative estimation of serum and salivary ferritin levels was performed by solid-phase ELISA. Hemoglobin levels were also estimated to confirm the anemic status of the patient. Data were statistically analyzed using SPSS software version 19. Results There was increased salivary ferritin level in patients with IDA. A negative significant correlation was found between serum hemoglobin and both salivary ferritin level and salivary/serum ferritin ratio, and a significant negative correlation between serum and salivary ferritin levels. Conclusion Salivary ferritin is a noninvasive method for the detection of IDA with a good predictive effect.

Novel Inflammatory-Nutritional Biomarkers as Predictors of Histological Activity in Crohn's Disease.

There has increasingly been an interest in histological remission as a therapeutic endpoint in inflammatory bowel disease. The aim of this study was to evaluate the utility of a variety of inflammatory - nutritional markers for predicting histological disease activity in patients diagnosed with Crohn's disease. Patients with Crohn's disease that had requisite endoscopic, pathological, and laboratory data were retrospectively enrolled in the study. Relevant clinical, laboratory, endoscopic, and pathological data were abstracted. The neutrophil:lymphocyte ratio (NLR), lymphocyte:monocyte ratio (LMR), platelet:lymphocyte ratio (PLR), red blood cell distribution width (RDW), modified Glasgow Prognostic score (mGPS), Prognostic Nutritional Index (PNI), Geriatric Nutritional Risk index (GNRI), CRP/Albumin ratio (CAR), Iron:Ferritin ratio (Fe:F) and the Systemic immune inflammation index (SII) were calculated. The cohort was stratified by presence of histological disease on colonoscopy, and groups were compared with appropriate statistical methods. When comparing patients without histological disease to those with disease, there was a statistically significant difference in CAR (2.9 ± 1.5 vs. 4.2 ± 2, p = 0.001), RDW (13.4 ± 1.3 vs. 14.5 ± 1.8, p = 0.008), PNI (52.4 ± 6.2 vs. 47.4 ± 9.3, p = 0.03), and mGPS (0.2 ± 0.4 vs. 0.6 ± 0.7, p = 0.01). For predicting histological activity, ROC analyses indicated an optimal cutoff of 0.3 for CAR (AUC 0.8, PPV 90.5%), 13.5 for RDW (AUC 0.7, PPV 84.1), 86.1 for PNI (AUC 0.7, PPV 86.1) and > 0 for mGPS (AUC 0.6, PPV 85.2%). The NLR, LMR, PLR, GNRI, Fe: F, and SII did not meet statistical significance (p = 0.4, 0.08, 0.2, 0.5, 0.6, and 0.3, respectively). We report on ten biomarkers, many of them never studied in Crohn's disease, which can help in predicting the presence of active histological disease. Larger prospective studies are needed to investigate the utility of these biomarkers alone and in combination.

Mild COVID-19 infection-predicting symptomatic phase and outcome: A study from AIIMS, New Delhi.

Context:Comprehensive management of mild COVID infection calls for better understanding of symptomatology in these group of patients as well as early identification and close monitoring of patients at risk, data on which is limited.Aim:To study association between inflammatory markers and clinical presentation with progression of disease and the duration of resolution of symptoms.Settings and Design:This is a retrospective study that has been conducted at a designated COVID -19 medical ward at AIIMS, New DelhiMethods and Material:Fifty healthcare workers and their dependents who were admitted with asymptomatic and mild COVID-19 infection were included. Their records were retrospectively reviewed, entered into a predesigned proforma and analyzed.Results:A total of 50 participants were included in the study of which 70% were healthcare workers. The patients were admitted with mild COVID illness out of which 22 (44%) were males. Most common symptom at presentation was fever (72%). Among patients who had mild disease versus those who progressed to moderate illness (n = 3), the patients with moderate illness were older [mean (SD): 57.33 (10.21) vs. 36.13 (14.05); P = 0.014] and had a longer duration of hospital stay [17 (1.41) days vs. 11.20 (3.86) days; P = 0.04]. Inflammatory markers, C-Reactive Protein (CRP) [2.46 vs. 0.20 (P = 0.024)], and Ferritin [306.15 vs. 72.53 (P = 0.023)] were higher in patients with moderate illness. There is also a significant correlation between the number of days taken for symptoms to resolve with Serum Ferritin (P = 0.007), CRP (P = 0.0256), and neutrophil lymphocyte ratio (NLR) (P = 0.044).Conclusions:Acute phase reactants/Inflammatory markers serve as good indicators of time taken to resolution of symptoms in acute COVID infection. NLR is a simple and inexpensive method to provide insight into symptomatic phase. These may be utility tools for primary care physician in the management in periphery and timely decision.

Анемия при воспалительных заболеваниях кишечника: патофизиология, диагностика и лечение

Anaemia is a common secondary syndrome in gastroenterological diseases. Anaemia in patients with inflammatory bowel disease (IBD) is observed in two thirds of patients, which significantly affects the quality of life. Anaemia in IBD has a complex pathogenesis. The most common types of anaemia in patients with IBD are iron deficiency anaemia (IDA) and anaemia of chronic disease, which are often combined. In most cases, laboratory tests can successfully diagnose iron deficiency, in cases when difficulties with differential diagnosis arise, the recently established indicators can be used, such as the soluble transferrin to ferritin ratio or the percentage of hypochromic red blood cells. In the treatment of IDA in patients with IBD, it is very important both to control intestinal inflammation and to correct iron deficiency. Oral iron supplements can be used in patients with mild anaemia and without inflammatory activity, but intravenous iron infusion should be chosen as a first line therapy in patients with haemoglobin &lt; 10 g/dl, in patients with active IBD, in patients with intolerance of oral drugs, and in cases when a fast response is not required. Erythropoietin is needed (in combination with intravenous iron infusion) in patients with anaemia to manage functional iron deficiency, while blood transfusion is restricted to refractory cases or acute, life-threatening conditions. Key words: anaemia, inflammatory bowel disease, iron deficiency anaemia, iron supplements, pathogenesis of anaemia

Altered Iron Parameters and Hepcidin Levels in a General Population: Lessons from the CHRIS Study

Introduction Environmental and genetic factors may lead to iron accumulation, causing irreversible organ damage. Homozygosity for the C282Y (C282Y +/+) and compound heterozygosity for the C282Y and H63D (C282Y-H63D) mutations of the HFE gene are associated with susceptibility to iron overload (IO). However, their clinical and biochemical expression is heterogeneous, with some patients showing only an increase of transferrin saturation (TSAT) for life, and others developing severe liver disease at a young age. Rarely, IO occurs in subjects without HFE-mutations or other acquired factors (e.g. alcohol intake, hemolysis, etc.). In these cases, non-HFE hemochromatosis is suspected, but the diagnosis is challenging, based on invasive (i.e., liver biopsy) or poorly available (i.e., Next-Generation Sequencing) approaches. A defective production of the iron regulatory hormone hepcidin is the key pathogenetic factor in hereditary hemochromatosis, irrespective of the gene involved, but extensive studies evaluating its potential diagnostic role are still lacking. This project evaluated hepcidin levels in a large subpopulation from the Cooperative Health Research In South Tyrol (CHRIS) study. Here we explored in particular hepcidin levels in subjects with altered iron status parameters, and their role in the identification of subjects at major risk of developing IO. Patients and Methods Study Population. The CHRIS study is a population-based study carried out in South Tyrol (Northern Italy), whose general aims are reported in detail elsewhere (Pattaro C, J Transl Med 2015). Blood samples were tested for several biochemical and genetic parameters, including those related to iron status, such as TSAT, ferritin, and C282Y and H63D mutations. Hepcidin was measured in stored aliquots by a recently updated and validated mass spectrometry-based method in tandem with liquid chromatography (LC-MS/MS), able to distinguish the active hepcidin-25 isoform (Diepeveen LE, Clin Chem Lab Med 2019). Results Among 4,642 participants, 6 were C282Y +/+ and 30 were C282Y-H63D (hereinafter defined as "HFE-H subjects"). HFE-H subjects showed ferritin levels only slightly higher than those with apparent wild-type HFE-H genotype (92.7 vs. 76.0 ng/ml, p=0.29), significantly higher TSAT (46.6 vs. 28.9%, p&lt;0.0001) and lower hepcidin levels (1.41 vs. 2.30 nmol/l, p=0.016) (Table 1). Defective production of hepcidin was suggested by the reduced hepcidin:ferritin ratio (1.53 vs. 3.02 pmol/ng, p&lt;0.0001), which was particularly low in C282Y +/+ (0.65 pmol/ng). Table 2 shows the prevalence of subjects with altered iron parameters (hyperferritinemia and/or increased TSAT), according to the HFE genotype. As concern HFE-H subjects, hyperferritinemia (i.e. &gt;200 or &gt;300 ng/ml in females and males, respectively) was detected in 16.7%, increased TSAT (&gt;45%) in 52.8% and both in 11.1%. A biochemical pattern suggestive of IO (ferritin&gt;500 ng/ml and TSAT&gt;50%) was seen only in 33.3% of C282Y +/+ and in 6.7% of C282Y-H63D, while 41.7% neither had hyperferritinemia nor increased TSAT, confirming the low penetrance of such genotype. Although HFE-H subjects displayed a tendency to increase hepcidin production according to iron deposits (mean level of 1.10 nmol/l in subjects without hyperferritinemia/increased TSAT vs. 3.5 nmol/l of subjects with IO), the hepcidin:ferritin ratio was significantly lower in phenotypically expressed HFE-H subjects (0.49 vs. 2.04 pmol/ng, p=0.014) (Table 3). On the other hand, 540 participants (11.7 percent) without HFE-H genotype had hyperferritinemia, 64 (1.4%) had both hyperferritinemia and increased TSAT, and 12 (0.3 percent) had biochemical signs strongly suggestive of IO (ferritin&gt;500 ng/ml and TSAT&gt;50%). The latters had reduced hepcidin:ferritin ratio (0.92 pmol/ng), a value comparable to that of HFE-H iron loaded subjects (p=0.048). Whole Exome Sequencing data are available for the majority of CHRIS subjects included in this project and will be analyzed in detail in these subpopulations. Conclusions Our data suggest that the hepcidin:ferritin ratio may actually represent a useful indicator of hemochromatosis irrespective of the HFE genotype, possibly driving an optimal use of second level genetic test. Disclosures Girelli: Vifor Pharma: Other: honoraria for lectures; Silence Therapeutics: Membership on an entity's Board of Directors or advisory committees; La Jolla Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy.

Non Invasive Evaluation of Bone Marrow Activity in Patients with Sickle Cell Disease: Correlation with Disease Features, Genotype, Markers of Erythropoiesis, Iron Metabolism and Hydroxyurea Treatment

Background: Sickle cell disease (SCD) is an inherited hemoglobinopathy characterized by pathological polymerization of hemoglobin, increased red cell rigidity and poor microvascular blood flow with consequent tissue ischemia and infarction. Thus, hemolytic anemia, vaso-occlusion and vasculopathy are the hallmarks of its clinical presentation. The transferrin receptor (TfR) mediates the transport of iron into cells and the circulating TfR can be measured as soluble transferrin receptor (sTfR). sTfR levels are frequently used to establish the diagnosis of iron deficiency anemia, especially in the context of inflammation, but they also reflect bone marrow erythropoietic activity (BMA) and mass. Erythropoietic activity has been found to be the most important determinant of sTfR levels. In this context, we aimed to study and evaluate bone marrow activity in patients with compound heterozygous HbS and beta-thalassemia (HbS/βthal) based in sTfR measurements and explore possible correlations with of key features of the disease such as: the hemolytic component, vaso-occlusive crises (VOC), acute chest syndrome, venous thrombosis, arterial thrombosis including stroke, avascular necrosis, pulmonary hypertension, hydroxyurea therapy, inflammation and renal injury. along with other biomarkers of erythropoiesis and iron metabolism such as Placental Growth Factor (PlGF), Growth Differentiation Factor-15 (GDF-15), Ferritin and Hepcidin-25. Patients and Methods: Ninety adult Caucasian patients with HbS/βthal [49 patients under hydroxyurea (HU+) treatment and 41 patients without hydroxyurea (HU-) treatment], were included in this study, while 22 apparently healthy individuals of similar age and gender served as controls. None of the patients has received any transfusions at least 6-monthes before enrollment in the study. Along with hematologic and blood chemistry parameters determination, levels of circulating sTfR, PlGF, GDF-15 and Hepcidin-25 were measured in patients with HbS/βthal and controls using RUO and IVD immunoenzymatic techniques. BMA activity was calculated from the established formula: patient-sTFR/meanControl-sTFR. Results: We found that: sTfR levels were markedly elevated in all patients with HbS/βthal compared to controls (4.8±2.2 vs. 1.0±0.2 mg/L, p&lt;0.001), resulting in a 1.6-11.9 fold increase of BMA. No correlation was found between BMA and disease features as well as regarding hydroxyurea treatment BMA (p&gt;0.434). BMA correlated significantly with the markers of the erythropoietic and hemolytic component such as: Hemoglobin (r=-0.434, p&lt;0.001); Reticulocyte Production Index (r=0.645, p&lt;0.001); LDH (r=0.570, p&lt;0.001); Billirubin (r=0.540, p&lt;0.001), PlGF (r=0.597, p&lt;0.001) and Hb A levels (r=-0.493, p&lt;0.001), while no correlation was found between BMA and Hb F levels. Furthermore, BMA values correlated significantly only with GDF-15 (r=0.466, p&lt;0.001), while interestingly no correlation was found between BMA and Ferritin and Hepcidin-25 levels alone (r=0.101, p&gt;0.351 and r=-0.043, p&gt;0.710, respectively), but a negative correlation was found between BMA and Hepcidin-25/Ferritin ratio, (r=-0.330, p=0.005). Conclusions: Our findings demonstrate that all patients with HbS/βthal studied have a significantly increased degree of erythroid BMA as assessed by measurements of sTfR levels. Erythroid BMA correlated significantly with Hepcidin/Ferritin ratio, which is an index of the degree of Hepcidin expression relative to iron overload. The correlation of erythroid BMA with Hb A levels, indicate the important role of βthal genotype in HbS/βthal disease. Furthermore, BMA is not related to hydroxyurea therapy and/or iron metabolism parameters in these patients. This implicates a likely complex action of hydroxyurea, which causes intermittent cytotoxic suppression of erythroid progenitors and cell stress signaling. The latter affects erythropoiesis, leading to recruitment of erythroid progenitors with increased HbF levels, although the number of erythroid progenitors -the main source of sTfR- remains stable. Disclosures Voskaridou: Genesis: Consultancy, Research Funding; Protagonist: Research Funding; Celgene Corporation: Consultancy, Research Funding; Acceleron: Consultancy, Research Funding; Addmedica: Membership on an entity's Board of Directors or advisory committees.

Does Gene Therapy in Beta Thalassemia Normalize Novel Markers of Ineffective Erythropoiesis and Iron Homeostasis?

BACKGROUND: Ineffective erythropoiesis in thalassemia alters iron homeostasis, predisposing to systemic iron overload. Successful allogeneic hematopoietic stem cell transplantation (HSCT) in thalassemia major corrects anemia, should eliminate ineffective erythropoiesis (IE) and normalize iron homeostasis (IH). Whether gene therapy (GT) will fully correct IE and IH is not known. This cross-sectional observational study evaluated the iron status of patients with beta thalassemia following HSCT or GT, and compared them with cohorts of patients with thalassemia intermedia (TI) or transfusion-dependent thalassemia (TDT) using recently introduced biomarkers along with imaging studies and other clinical assessments to better understand and characterize IE and IH across groups. METHODS: We evaluated a convenience sample of 29 participants with beta thalassemia (median age 25 years, IQR 21-35; females 55%; Asian 52%). Participants in the HSCT (n=6) and GT (n=10) groups were evaluated on average 116.5 and 46.9 months following cell infusion, respectively. TDT patients (n= 9) were evaluated pre-transfusion and off iron chelation for at least 7 days, and TI (n=4) were un-transfused or not transfused in &amp;gt;3 years. Clinical lab assessments and MRI R2*/ T2* to assess heart and liver iron burden including post-processing, were performed using local clinical protocols. ELISAs for hepcidin, erythroferrone (Erfe) and GDF-15 were performed in a blinded manner. RESULTS: Median values for all IE and IH parameters tested were normal in the HSCT group, and were significantly lower than in all other groups. There were significant differences among all groups for hemoglobin (p=0.003), erythropoietin (Epo) (p=0.03), serum ferritin (SF) (p=0.01), transferrin (p=0.006), soluble transferrin receptor (sTfR) (p=0.02), serum hepcidin: serum ferritin (H:F) ratio (p=0.006), Erfe (p=0.001), GDF15 (p=0.003), and liver iron content (LIC) by MRI R2* (p=0.02). H:F ratio, a surrogate for predisposition to systemic iron loading, inversely correlated with Erfe (rs= -0.85, p&amp;lt;0.0001), GDF15 (rs= -0.69, p=0.0001) and liver R2* (rs= -0.66, p=0.0004). In a multivariate analysis, adjusted for gender and race, H:F ratio and Epo levels predicted Erfe and GDF15 (p=0.05 and p=0.06; p=0.01 and p=0.05), respectively. Even after excluding GT patients that are not transfusion independent (N=2), SF, Epo, sTfR and hepcidin remain abnormal in the GT group, and there were no significant differences in these parameters between GT and TDT. However, novel biomarkers of IH and IE suggested lower ineffective erythropoiesis in GT compared to TDT (median (IQR) Erfe, 12 (11.6-25.2) vs. 39.6 (24.5-54.7), p=0.03; GDF15, 1909.9 (1389-4431) vs. 8906 (4421-12331), p=0.02), respectively. Erfe and GDF15 were also lower in GT compared to TI, however these differences did not reach statistical significance. There were no differences in hepcidin, ferritin, or H:F by race, however Erfe and GDF15 were significantly lower in Asians compared to non-Asians (p=0.006 and p=0.02, respectively). CONCLUSION: Nearly 4 years post infusion, most subjects with TDT treated with GT are transfusion independent with near normal hemoglobin, however, studies in this limited cohort using conventional measures suggest IE and IH improve, particularly when transfusion support is no longer needed, however they remain abnormal compared to HSCT recipients, who using these parameters appear to be cured. STfR did not detect differences, however GDF15 and Erfe were more sensitive assays that could demonstrate significant improvement in IE and IH with GT compared to TDT. Contribution to IE by uncorrected stem cell populations post GT cannot be determined. Transduction enhancement and other recent improvements to GT may yield different results. Longitudinal studies are needed to determine if thalassemia patients treated with GT will have ongoing IE predisposing to systemic iron overload. Disclosures Thompson: bluebird bio, Inc.: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Baxalta: Research Funding. Ganz:Intrinsic LifeSciences: Consultancy, Equity Ownership. Nemeth:Intrinsic LifeSciences: Consultancy, Equity Ownership; Silarus Therapeutics: Consultancy, Equity Ownership; Keryx: Consultancy; Ionis Pharmaceuticals: Consultancy; La Jolla Pharma: Consultancy; Protagonist: Consultancy.

Iron status and hepcidin levels as potential regulators of haemoglobin homeostasis in overweight and obese women of childbearing age.

ObjectivesOverweight is considered a risk factor for anaemia. However, the mechanisms underlying anaemia development in overweight and obese people remain unclear. This study analysed the correlation of iron status (soluble transferrin receptor [sTfR]/log ferritin ratio) and hepcidin levels with haemoglobin (Hb) levels in overweight and obese women of childbearing age.MethodsIn this cross-sectional study, we recruited 66 women aged 20–29 years with a body mass index ≥23 kg/m2. We gathered data on informed consent, demographic characteristics, questionnaire responses, anthropometric and laboratory values. A Spearman correlation test was performed to determine the correlation.ResultsThe mean levels of ferritin and sTfR were 10.2 ± 8.12 and 22.2 ± 7.96 ng/ml, respectively, and the mean sTfR/log ferritin ratio was 29.3 ± 17.65 nmol/L. The mean hepcidin levels were 9.0 ± 3.05 ng/ml. In total, 75.8% of subjects had low ferritin levels, high sTfR (51.5%) levels, and a high sTfR/log ferritin ratio (87.9%). The sTfR levels (r = −0.359; p = 0.003) and sTfR/log ferritin ratio (r = −0.375; p = 0.002) were negatively correlated with Hb levels. There was no correlation between the levels of hepcidin and Hb (r = −0.140; p = 0.264), but there was a positive correlation between ferritin and Hb levels (r = 0.350; p = 0.004).ConclusionThis study showed a correlation between iron status and Hb levels in overweight and obese women of childbearing age. All the women had erythropoiesis with iron deficiency anaemia. We recommend that overweight and obese women undergo further iron parameters for the detection of early anaemia. In this group, the consumption of foods that enhance iron absorption, such as ascorbic acid, should be encouraged.

The Relation between Serum Hepcidin, Ferritin, Hepcidin: Ferritin Ratio, Hydroxyurea and Splenectomy in Children with β-Thalassemia.

BACKGROUND:Hepcidin, a small peptide hormone, is established as the main regulator of iron homeostasis.AIM:To estimate serum hepcidin, ferritin, and hepcidin: ferritin ratio in β-thalassemia patients and to determine the effect of splenectomy and hydroxyurea on serum hepcidin.METHODS:A study was conducted on 30 thalassemia major (βTM), 29 thalassemia intermedia (βTI) and 29 healthy children’s controls. Data were collected by patient interviewing where detailed history-taking and thorough clinical examinations were carried out. Serum ferritin and hepcidin were measured by ELISA assay (Bioneovan Co. Ltd Beijing, China).RESULTS:Βeta-thalassemia patients had higher serum ferritin, serum hepcidin and lower Hb and hepcidin: ferritin ratio compared to the controls (p < 0.001, 0.010, 0.001, 0.001) respectively. Β-TM patients had higher mean serum hepcidin and serum ferritin compared to β-TI, with statistically significant difference (P = 0.042, P < 0.001, respectively). Twenty-one patients out of 29 βTI was on hydroxyurea therapy; these patients had significantly lower levels of serum ferritin (P < 0.004) and significantly higher levels of Hb (P < 0.004). Serum ferritin was statistically significantly higher in splenectomized patients P < 0.009. Serum hepcidin level was insignificantly higher in splenectomized patients than non-splenectomized patients (21.6 ± 14.75, 17.76 ± 10.01 ng/mL). Hepcidin showed a significantly positive correlation with hepcidin: ferritin ratio in all studied groups.CONCLUSION:Serum hepcidin was elevated in β-thalassemia children with more evident elevation in βTM patients. Splenectomy played no major role in hepcidin regulation. Knowing that hepcidin in serum has a dynamic and multi-factorial regulation, individual evaluation of serum hepcidin and follow up, e.g. every 6 months could be valuable, and future therapeutic hepcidin agonists could be helpful in management of iron burden in such patient.

Ferritin to Erythrocyte Sedimentation Rate Ratio: Simple Measure to Identify Macrophage Activation Syndrome in Systemic Juvenile Idiopathic Arthritis.

ObjectiveMacrophage activation syndrome (MAS) is a life‐threatening complication of systemic juvenile idiopathic arthritis (sJIA). Early diagnosis is critical. Classification criteria for MAS in sJIA perform less well in the setting of cytokine‐directed therapies. The goal herein was to explore a simple ratio of serum ferritin to the erythrocyte sedimentation rate (ESR) for diagnosis of MAS in the setting of sJIA, and to assess ferritin alone as a screening tool for identifying MAS of multiple etiologies.MethodsData from a large international cohort of sJIA patients with and without MAS, and from hospitalized patients with systemic infection (SI), were assessed for the ferritin:ESR ratio and ferritin alone to identify MAS among sJIA patients. Moreover, data from a smaller cohort of MAS patients associated with multiple etiologies and febrile hospitalized controls were explored. For both cohorts and controls, receiver operating characteristic curves (ROCs) for the ferritin:ESR ratio and ferritin alone were constructed, and areas under the curves (AUCs) were calculated. The Youden index was used to determine the optimal ferritin:ESR ratio and ferritin alone cut points for diagnosis.ResultsA ferritin:ESR ratio of 21.5 was 82% sensitive and 78% specific for diagnosing sJIA‐MAS versus active sJIA without MAS. Ferritin alone with a set sensitivity of 95% (screening tool) had an 89.3% specificity of identifying all‐cause MAS versus febrile hospitalized children.ConclusionThe ferritin:ESR ratio is a practical tool for diagnosing MAS among sJIA patients, and serum ferritin alone is a remarkable screening tool for identifying MAS among febrile hospitalized children.

Bioavailability of Iron Supplement Formulations by Bariatric Surgery Type: A Pilot Study (P23-013-19)

ObjectivesOur previous research demonstrated that ferrous sulfate, the gold standard iron supplement treats iron deficiency in bariatric surgery patients but wasn’t well tolerated. We also found that the bioavailability of iron supplements, assessed by a serum iron absorption test, predicts treatment response. The objective of the current study is to determine whether bariatric surgery type (gastric bypass [GB] and sleeve gastrectomy [SG]) or iron formulation type (inorganic ferrous sulfate versus and an organic, slow-release form of iron, called AspironTM) predicts iron supplement bioavailability. MethodsIron-deficient GB and SG females, ages 18–65 years, who had surgery at least 6 months previously, participated in an 8-hour iron absorption test. Participants were considered iron deficient if two of the following values were abnormal: serum transferrin receptor greater than 2012 mcg/L, ferritin below 30 mcg/L, total iron binding capacity above 370 mcg/dL, and a serum transferrin receptor: ferritin ratio greater than 500. Participants received a low-iron breakfast with a 65 mg iron supplement. We assessed serum iron every 30 minutes for 8 hours following the supplementation using a calorimetric assay (South Bend Medical Foundation, South Bend, IN). ResultsWe report our preliminary findings to date; the study is ongoing. Out of the 10 participants, 8 had GB and 2 had SG. Six of the GB patients and both SG patients received AspironTM, and two of the GB patients received ferrous sulfate. In GB participants, following ferrous sulfate, serum iron increased 80.5 ± 6.4 mcg/dL compared to baseline, whereas following AspironTM, serum iron increased 6.7 ± 4.6 mcg/dL compared to baseline (P = 0.000). Compared to the GB group, serum iron increased 58.5 ± 57.3 mcg/dL in the SG group following AspironTM supplementation (P = 0.037). ConclusionsOur preliminary findings suggest that AspironTM is not as bioavailable as ferrous sulfate in GB patients. AspironTM may be better absorbed in SG patients, indicating that it could be an effective treatment to reverse iron deficiency in the SG population. Funding SourcesCura Global Health Inc.

Circulating Iron Levels Interaction with Central Obesity on the Risk of Nonalcoholic Fatty Liver Disease: A Case–Control Study in Southeast China

Objectives: We aimed to evaluate the associations between body iron stores and the risk of nonalcoholic fatty liver disease (NAFLD) in a Chinese population and explore whether this effect may be modified by other factors. Methods: A 1: 1 frequency-matched case–control study was conducted, including 482 NAFLD cases and 490 gender- and age-matched controls. Serum levels of ferritin, hepcidin, and C-reactive protein were measured. Results: Multivariate logistic regression analysis showed that hepcidin was not associated with NAFLD risk; however, elevated serum ferritin was significantly associated with increased risk of NAFLD (adjusted OR 1.619, 95% CI 1.158–2.267), and hepcidin:ferritin ratio was significantly associated with decreased risk of NAFLD ­(OR­_adjusted 0.702, 95% CI 0.501–0.984). When stratified by gender, a significant association was found between elevated serum ferritin and hepcidin:ferritin ratio and NAFLD only for women (OR_adjusted 2.131, 95% CI 1.151–3.944 and OR_adjusted 0.414, 95% CI 0.219–0.781, respectively). A significant multiplicative interaction between central obesity and elevated serum hepcidin was observed (p < 0.05). Conclusions: Elevated serum ferritin and hepcidin:ferritin ratio are associated with NAFLD in a Chinese population. Although serum hepcidin is not associated with NAFLD, it may augment the risk effect of central obesity on NAFLD.

Malaria early in the first pregnancy: Potential impact of iron status

Low iron stores may protect from malaria infection, therefore improving iron stores in early pregnancy in line with current recommendations could increase malaria susceptibility. To test this hypothesis we compared iron biomarkers and red cell indices in nulliparae and primigravidae who participated in a randomized controlled trial of long-term weekly iron supplementation. Cross-sectional and longitudinal data analysis from a randomized controlled trial of long-term weekly iron supplementation in rural Burkina Faso. Malaria parasitaemia was monitored and biomarkers and red cell indices measured at study end-points: plasma ferritin, transferrin receptor (sTfR), zinc protoporphyrin, hepcidin, sTfR/log10 ferritin ratio, body iron, haemoglobin, red cell distribution width; mean corpuscular haemoglobin concentration/volume, and C-reactive protein. Correlation coefficients between biomarkers and red cell indices were determined. A regression correction approach based on ferritin was used to estimate iron body stores, allowing for inflammation. Body iron differences were compared between nulliparae and primigravidae, and the association determined of iron biomarkers and body iron stores with malaria. Iron and haematological indices of 972 nulliparae (mean age 16.5 years) and 314 primigravidae (median gestation 18 weeks) were available. Malaria prevalence was 54.0% in primigravidae and 41.8% in nulliparae (relative risk 1.28, 95% CI 1.13-1.45, P<0.001), anaemia prevalence 69.7% and 43.4% (P<0.001), and iron deficient erythropoiesis (low body iron) 8.0% and 11.7% (P=0.088) respectively. Unlike other biomarkers the sTfR/log10 ferritin ratio showed no correlation with inflammation as measured by CRP. Most biomarkers indicated reduced iron deficiency in early pregnancy, with the exception of haemoglobin. Body iron increased by 0.6-1.2mg/kg in early gestation, did not differ by malaria status in nulliparae, but was higher in primigravidae with malaria (6.5mg/kg versus 5.0mg/kg; relative risk 1.53, 95% CI 0.67-2.38, P<0.001). In primigravidae, early pregnancy haemoglobin was not a good indicator of requirement for iron supplementation, which could be detrimental given the association of better iron status with increased malaria infection. clinicaltrials.gov:NCT01210040. Until placed in a public repository, data relating to the current study can be requested from the corresponding author and will be made available following an end user data agreement and sponsor approval.

Iron status determination in individuals with Helicobacter pylori infection: conventional vs. new laboratory biomarkers

Background Helicobacter pylori has been associated with iron deficiency (ID). This study is aimed at investigating ID with conventional (ferritin, transferrin saturation [TSAT]) and new biomarkers (soluble transferrin receptor [sTfR], sTfR/log ferritin, reticulocyte hemoglobin content [CHr], hepcidin-25) in patients sub-grouped by the presence or absence of H. pylori infection. Methods In total, 200 consecutive outpatients, who were referred for the H. pylori 13C-urea breath test (13C-UBT), underwent blood testing for ID. Additionally, Thomas-plot (TP)-analyses (sTfR/log ferritin, CHr) were calculated. Results Fifty-three and 147 individuals were found with and without H. pylori infection, respectively. Patients with H. pylori infection showed a higher sTfR concentration (p<0.02) and a higher sTfR/log ferritin ratio (p<0.05). Based on a ferritin <30 μg/L and/or a TSAT <20%, 25/53 (47.2%) patients with H. pylori infection and 63/147 (42.9%) without H. pylori infection showed ID. Based on TP-analyses, 10/53 (18.9%) patients with and 17/147 (11.6%) without H. pylori infection were identified with ID. Completed eradication therapy tended to be associated with functional ID. Conclusions Helicobacter pylori infection was associated with significantly higher plasma sTfR concentrations and sTfR/log ferritin ratios. Patients with H. pylori eradication therapy were more often detected with functional ID compared to patients without eradication therapy, when using the new biomarkers.