Certain Associations Between Iron Biomarkers and Total and γ' Fibrinogen and Plasma Clot Properties Are Mediated by Fibrinogen Genotypes

Introduction: Evidence for the relationship between body iron and cardiovascular disease (CVD) is inconsistent and mechanisms involved remain poorly understood. Therefore, we first investigated whether there are linear or non-linear relationships between iron status and total and γ' fibrinogen as well as plasma fibrin clot properties and, second, determined whether there are interactions with iron biomarkers and fibrinogen and FXIII single nucleotide polymorphisms (SNPs) in relation to fibrinogen concentration and functionality.Methods: In this cross-sectional analysis of 2,010 apparently healthy Black South Africans we quantified total and γ' fibrinogen, serum iron, ferritin and transferrin using standardized methods and calculated transferrin saturation (TS). Clot architecture and lysis were explored with a global analytical turbidity assay. The SNPs were determined through an Illumina BeadXpress® platform.Results: Total, but not %γ', fibrinogen negatively correlated with serum iron concentrations, although both decreased over iron tertiles. %γ' fibrinogen correlated negatively with transferrin and decreased over the transferrin tertiles. A weak negative association between total fibrinogen and TS was detected with fibrinogen decreasing over the TS tertiles and categories based on TS. Lag time correlated positively with transferrin and increased over transferrin tertiles, when adjusting for fibrinogen. Before adjusting for fibrinogen, lag time was shorter in those with adequate iron status based on TS than other iron subcategories. Clot lysis time (CLT) negatively correlated with ferritin and was longer in the first than in the third ferritin tertile. Among iron status categories based on ferritin, only CLT differed and was longer in those with adequate iron than with iron-overload. CLT negatively correlated with TS, albeit weakly, shortened over the TS tertiles and was shorter in those with adequate iron based on TS categories. Interactions were observed between FGB SNPs and some of the markers of iron status investigated, in relation to the clot properties with the most prominent associations detected in homozygous carriers of the variant alleles for whom increased iron status was more beneficial than for those harboring the wild-type alleles. Iron modulated the influence of the SNPs so that for the majority iron was beneficial in respect of clot properties, but even more so for a minority group harboring specific variant alleles.Conclusion: This is the first large-scale epidemiological study to relate fibrinogen concentration and functionality to markers of iron status and to take genetic factors into consideration. We have detected a relationship between iron biomarkers and fibrinogen as well as clot characteristics that are influenced by the genetic make-up of an individual.

Download Full-text

Assessment of Gastrointestinal Symptoms and Non-transferrin Bound Iron After Oral Ferrous Sulfate and Iron-enriched Aspergillus Oryzae Supplementation in Women (P24-039-19)

Current Developments in Nutrition ◽

10.1093/cdn/nzz044.p24-039-19 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

Author(s):

Amanda Bries ◽

Chong Wang ◽

Brian Wels ◽

Isaac Agbemafle ◽

Olivia Meier ◽

...

Keyword(s):

Oxidative Stress ◽

Side Effects ◽

Ferrous Sulfate ◽

Serum Iron ◽

Iron Supplementation ◽

Iron Status ◽

Transferrin Saturation ◽

Oral Iron ◽

Deficiency Anemia ◽

Iron Supplements

Abstract Objectives Iron deficiency anemia (IDA) is a widespread nutritional deficiency. Iron supplementation with ferrous sulfate (FeSO4) is the most common strategy to treat IDA; however, the compliance with daily FeSO4 administration is poor, due to contraindicating side effects. Previously, we have reported that A. oryzae (Ultimine®; ULT) is a novel iron source. Therefore, the objective of this study was to determine the biochemical assessment, non-transferrin bound iron (NTBI) and commonly related gastrointestinal side effects to assess the safety of A. oryzae compared to FeSO4. Methods Female participants (n = 16) with serum ferritin concentrations 40 µg/L were randomized to a double-blind, 9-wk cross-over study with a 3-wk placebo washout period between treatments. Oral iron supplements (65 mg Fe), FeSO4 and ULT were administered for 21 consecutive days for each subject. Side effect questionnaires were collected 3d/wk over the 9-wk study period. Side effects and biochemical markers (nausea, heartburn, abdominal pain, fatigue, headache, diarrhea, constipation, oxidative stress and liver and kidney function) from iron supplementation were evaluated, along with serum iron, % transferrin saturation (TS) and NBTI 8 h curves. Results Serum iron, TS, and NTBI were all markedly higher with FeSO4 at each time-point from 2–8 hours (P < 0.001) compared to ULT, whereas NTBI was undetected. Among treatments, FeSO4 resulted in higher inflammation, though not statistically significant. Compliance based on returned pills was higher with ULT (97.3%) than placebo and FeSO4 (95.2% and 93.2%, respectively). Subjects taking FeSO4 reported abdominal discomfort 2% more than ULT, which was not significantly different. FeSO4 caused marginally higher incidence of combined nauseation, constipation and diarrhea when subjects were taking FeSO4 (P < 0.07). Iron status was maintained similarly by both oral iron supplements. Oxidative stress, inflammation, kidney and liver function markers were not elevated with ULT supplementation, suggesting safety of its consumption. Conclusions Better compliance and less gastrointestinal related side effects were reported with ULT compared to FeSO4, while maintaining normal iron status. Our data suggests ULT is a safe oral iron supplement for treatment of IDA. Funding Sources Cura Global Health, Inc.

Download Full-text

The Haptoglobin 2-2 Phenotype Affects Serum Markers of Iron Status in Healthy Males

Clinical Chemistry ◽

10.1093/clinchem/46.10.1619 ◽

2000 ◽

Vol 46 (10) ◽

pp. 1619-1625 ◽

Cited By ~ 62

Author(s):

Michel R Langlois ◽

Marie-Elise Martin ◽

Johan R Boelaert ◽

Carole Beaumont ◽

Youri E Taes ◽

...

Keyword(s):

Serum Iron ◽

Iron Status ◽

Transferrin Saturation ◽

Peripheral Blood Monocyte ◽

Serum Markers ◽

Starch Gel Electrophoresis ◽

Iron Storage ◽

Hemoglobin Binding ◽

Healthy Males

Abstract Background: Human iron status is influenced by environmental and genetic factors. We hypothesized that the genetic polymorphism of haptoglobin (Hp), a hemoglobin-binding plasma protein, could affect iron status. Methods: Reference values of serum iron status markers were compared according to Hp phenotypes (Hp 1-1, Hp 2-1, Hp 2-2; determined by starch gel electrophoresis) in 717 healthy adults. Iron storage was investigated in peripheral blood monocyte-macrophages by measuring cytosolic L- and H-ferritins and by in vitro uptake of radiolabeled (125I) hemoglobin-haptoglobin complexes. Results: In males but not in females, the Hp 2-2 phenotype was associated with higher serum iron (P <0.05), transferrin saturation (P <0.05), and ferritin (P <0.01) concentrations than Hp 1-1 and 2-1, whereas soluble transferrin receptor concentrations were lower (P <0.05). Moreover, serum ferritin correlated with monocyte L-ferritin content (r = 0.699), which was also highest in the male Hp 2-2 subgroup (P <0.01). In vitro, monocyte-macrophages took up a small fraction of 125I-labeled hemoglobin complexed to Hp 2-2 but not to Hp 1-1 or 2-1. Conclusions: The Hp 2-2 phenotype affects serum iron status markers in healthy males and is associated with higher L-ferritin concentrations in monocyte-macrophages because of a yet undescribed iron delocalization pathway, selectively occurring in Hp 2-2 subjects.

Download Full-text

Iron Status in Malnourished Children : A Cross Sectional Study

Chattagram Maa-O-Shishu Hospital Medical College Journal ◽

10.3329/cmoshmcj.v13i3.21024 ◽

2014 ◽

Vol 13 (3) ◽

pp. 50-53

Author(s):

Shormin Ara Ferdousi ◽

Rajat Sanker Roy Biswas ◽

Nayan Kanti Paul ◽

Mohammed Rezaul Karim

Keyword(s):

Serum Iron ◽

Iron Status ◽

Transferrin Saturation ◽

Age Groups ◽

Cross Sectional Study ◽

Iron Level ◽

Serum Iron Level ◽

Cross Sectional ◽

Malnourished Children ◽

Different Types

Objectives: Malnutrition is a common condition among children and iron status varies in different types of malnutrition. So the present study is aimed to find the different iron status among severe malnourished children in our context. Methods: A hospital based cross sectional study was done in the Paediatrics ward Chittagong Medical College Hospital in a period of 6 months from January to July 2013 among the 50 cases of malnourished children of age range between 1 to 5 years and Weight for Height Z score(WHZ) was <-2 SD. Sampling technique was continuous purposive sampling. Venous blood was collected to assay the different iron profile mainly serum iron level, total iron binding capacity(TIBC) and transferrin saturation(TSAT). Data was analyzed after correction by SPSS-19. Results: Among the 50 study children of different age groups 15 patients were 1 to 2 years, 18 patients were 2 to 3 years, 10 patients were 3 to 4 years and 7 patients were at 4-5 years of age groups. Among the patients, 29 (58%) of patients were female and 21(42%) of the patients were male. Most of the children were from the families of low socioeconomic status 38(76%). 2(4%) children were from upper middle class who had step mother. Among the selected patients the dominating clinical features were anemia was found among 45(90%) of patients which was mild(66.6%), moderate(26.6%) and severe(6.6%). Skin changes(32%), eye changes (10%) and hair changes(48%) were also found. Among the 50 study subjects prelacteal feeding was given among 43(86%) children, breast feeding was given 45(90%), exclusive breast feeding was given to 24(48%) of children and complementary feeding after 6 months was given to 29(58%) patients. Among the 50 patients -2 to -3 SD weight for height was found in 20(40%) patients and <-3 SD was found in 30(60%) patients. Most of the children was found to have Mid Upper Arm Circumference (MUAC) 115-125 mm(50%). Iron status was measured among all patients where serum iron level was found 77.72 ± 11.22 mcgm/dl, TIBC was found 340.07 ± 22.67 mcgm/dl and transferrin saturation was found 22.38 ± 2.9 %. Iron status were measured among the different types of malnutrition where serum iron level and transferrin saturation was high among all patients with malnutrition while TIBC was lower than standard level in all patients. Different biochemical status were measured among the different types of malnutrition where serum total protein, serum albumin, Hb% were lower than standard level in all patients.Conclusion: Change in different iron status is a common findings in malnourished children. Screening of all children for anemia and providing iron and folic acid (IFA) or multiple micronutrients (MMN) supplements to children and Infant and Young Child Feeding (IYCF) should be addressed at all level to overcome the situation.DOI: http://dx.doi.org/10.3329/cmoshmcj.v13i3.21024

Download Full-text

P6231Iron status and risk of cardio-metabolic diseases in European adults: a Mendelian randomization study

European Heart Journal ◽

10.1093/eurheartj/ehz746.0833 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

W Gan ◽

D Bennett ◽

A Mahajan ◽

H Du ◽

Z Chen ◽

...

Keyword(s):

Serum Iron ◽

Metabolic Diseases ◽

Mendelian Randomization ◽

Iron Status ◽

Transferrin Saturation ◽

Sensitivity Analyses ◽

European Ancestry ◽

Research Centre ◽

Inverse Association ◽

Total N

Abstract Background Observational studies have reported conflicting results about the associations of iron status with risk of cardio-metabolic diseases but such studies are constrained by confounding and reverse causality. Purpose To assess the causal relevance of iron status biomarkers (transferrin, serum iron, and ferritin) for risk of coronary artery diseases (CAD), ischaemic stroke (IS), and type 2 diabetes (T2D), using Mendelian randomization (MR). Methods Effect size estimates for genetic variants associated with iron status biomarkers were obtained from the Genetics of Iron Status consortium (transferrin saturation, serum iron, and ferritin: n=48,972). The corresponding effects of these variants on the risk of CAD, IS and T2D were obtained from a meta-analysis of unrelated participants of European ancestry in the UK Biobank (UKB), together with previously recruited participants in CARDIOGRAMplusC4D (total n=90,377 CAD cases), MEGASTROKE (total n=43,381 IS cases) and DIAGRAM (total n=74,124 T2D cases), respectively. The main analysis used a two-sample inverse-variance weighted MR, while the sensitivity analyses used weighted-median, weighted-mode, MR-PRESSO, and MR-Egger approaches. Results MR analysis demonstrated significant inverse association of each of the three genetically-instrumented iron status biomarker with risk of CAD (transferrin saturation OR=0.96 [95% CI: 0.92–0.99], p=0.02; serum iron OR=0.93 [0.89–0.97], p=0.001; and ferritin OR=0.86 (0.79–0.94), p=0.001, per 1 SD higher level). In contrast, these iron status biomarkers showed positive associations with risk of T2D (transferrin saturation OR=1.06 [1.01–1.11], p=0.01; serum iron OR=1.06 [0.99–1.13], p=0.07; and ferritin OR=1.12 [0.99–1.26], p=0.06, per 1 SD higher level). There was positive, but non-significant, association of IS with each of the iron status biomarker analysed. Sensitivity analyses using several different MR approaches yielded concordant results. Conclusions Among European adults, iron status appeared to have causal associations, but in opposite directions, with the risk of CHD and T2D. Our findings highlight the need for caution about strategies for advocating iron supplementation in individuals with normal haemoglobin levels for prevention of CAD. Acknowledgement/Funding British Heart Found, Medical Research Council, Wellcome Trust, NIHR Biomedical Research Centre, Oxford

Download Full-text

Interaction Between Genotypes for HFE and TFR2 Genes Mutations and Iron Status in Brazilian Blood Donors

Blood ◽

10.1182/blood.v112.11.5382.5382 ◽

2008 ◽

Vol 112 (11) ◽

pp. 5382-5382

Author(s):

Rodolfo D Cancado ◽

Paulo CJL Santos ◽

Samuel Rostelato ◽

Cristiane T Terada ◽

Iris Gonzales ◽

...

Keyword(s):

Serum Ferritin ◽

Serum Iron ◽

Blood Donors ◽

Binding Capacity ◽

Iron Status ◽

Hereditary Hemochromatosis ◽

Transferrin Saturation ◽

The Body ◽

Hfe Gene ◽

Automation System

Abstract Hereditary hemochromatosis (HH) is a disorder characterized by increased intestinal iron absorption, which leads to a progressive accumulation of iron in the body. This iron overload has been associated with mutations in HFE gene (C282Y, H63D and S65C) and other genes. The objectives of this study were to assess the frequencies of functional mutations in HFE and TFR2 genes and to investigate their relationship with the iron status in a sample of blood donors. Blood donors (n=542) were recruited at the Hemocenter of the Santa Casa Hospital, Sao Paulo, Brazil. The genotypes for HFE (C282Y, H63D and S65C) TFR2 (Y250X and Q690P) gene mutations were evaluated by PCR-RFLP. The concentrations of serum iron and total iron-binding capacity (TIBC) were measured by automation system Advia®(Bayer Diagnostics) and serum ferritin by Axsym System®(Abbott Laboratories). The frequencies of HFE 282Y, HFE 63D and HFE 65C alleles were 2.1, 13.6 and 0.6%, respectively. The frequency C282Y allele (2.1%) in Brazilian blood donors is lower than that observed in blood donors from Northern Europe (5.1 to 8.2%, P<0.05). The TFR2 250X and TFR2 690P alleles were not found in these subjects. The iron status was similar between HFE genotypes in women. However, men carrying HFE 282CY genotype had higher serum ferritin and lower TIBC concentrations when compared to the HFE 282CC genotype carriers. HFE 282CY genotype was also associated with higher transferrin saturation in men who donated blood at the first time. Moreover, male donors with HFE 63DD plus 63HD genotypes had higher serum iron and transferrin saturation when compared to those with HFE 63HH genotype. A relationship between HFE CY/HH/SS haplotype and lower TIBC concentrations was also found in men. The HFE 282Y and HFE 65C alleles were rare while the HFE 63D was frequent in blood donors. The mutations in TFR2 gene were not found in this study. The HFE 282Y and HFE 63D alleles were associated with alterations on iron status only in male blood donors.

Download Full-text

High Prevalence of Iron Deficiency In Anemic and Non Anemic Patients with Various Types of Cancer

Blood ◽

10.1182/blood.v116.21.5145.5145 ◽

2010 ◽

Vol 116 (21) ◽

pp. 5145-5145

Author(s):

Heinz Ludwig ◽

Georg Endler ◽

Brigitte Klement ◽

Wolfgang Hüubl ◽

Tim Cushway

Keyword(s):

Iron Deficiency ◽

Serum Ferritin ◽

Multiple Testing ◽

Serum Iron ◽

Iron Supplementation ◽

Complete Blood Count ◽

Clinical Symptoms ◽

Iron Status ◽

Transferrin Saturation ◽

Patients With Cancer

Abstract Abstract 5145 Introduction and aims: Iron deficiency as a major component in the pathogenesis of anemia in cancer is not acknowledged by most oncologists, possibly except when arising from GI blood loss. Iron deficiency is associated with clinical symptoms such as cognitive impairment, fatigue, and reduced exercise performance. New iron formulations are available that allow rapid iron supplementation with single infusions. This treatment could ameliorate symptoms of iron deficiency and correct anemia. Here, we studied iron parameters and their correlation with erythropoiesis and inflammatory markers in a large unselected cohort of patients with cancer. In addition, we investigated the suitability of serum ferritin and transferrin saturation (TSAT) as parameter for assessment of the iron status. Patients and methods: Data from 1627 patients (median age: 66.4 years, range: 20–97 years) presenting sequentially at the Center for Oncology and Hematology, Wilhelminenspital, Vienna between October 01, 2009 and January 26, 2010, have retrospectively been analyzed. Patients were at different stages of their disease or may not have had an established diagnosis at the time of testing. In patients with multiple testing during this period only the first sample taken was included. TSAT (n=1516), serum ferritin (n=887), serum iron, CRP, and complete blood count, were determined by using standard techniques. Commonly used definitions for absolute iron deficiency (AID), [TSAT <20% and serum ferritin <30ng/ml, in case serum ferritin was not available TSAT <10%] and for functional iron deficiency (FID), [TSAT <20% and serum ferritin ≥30ng/ml, in case serum ferritin was not available TSAT between 10 and 20%] have been applied. Fisher's exact test was used for comparison of frequencies and Pearson's product moment correlation coefficient for evaluation of correlation. Results: Table 1 shows the distribution of TSAT and serum ferritin categories in 1627 patients with cancer. AID was found in 116 patients (7.7%) of the 1516 patients for whom TSAT was available. Eighty-three (72%) of the AID patients presented with anemia (defined by hemoglobin <12g/dl). AID was most common in patients with colorectal and pancreatic cancer (12% and 11%, respectively), and not present in patients with testicular and prostate cancer (p=0.013). FID was diagnosed in 530 patients (35%) and 222 (42%) of them were found to be also anemic. Multivariate analysis revealed a statistically significant correlation between TSAT and serum ferritin (R=0.286, p<0.001), serum iron (R=0.874, p<0.001), hemoglobin (R=0.201, p<0.001) and CRP (R=-0.205, p<0.001) (figure 1). Serum ferritin, in contrast, did not correlate with serum iron (R=0.051, p=0.132), but correlated with hemoglobin (R=-0.259, p<0.001), TSAT (R=0.286, p<0.001), and CRP (R=0.396, p<0.001). Conclusion: AID (7.7%) and even more so FID (35%) are frequent co-morbidities in patients with various types of cancer. Seventy-two percent of patients with AID and 42% with FID presented with overt anemia. TSAT correlated closely with serum iron and hemoglobin levels and seems to be the preferred parameter for assessment of iron status in patients with chronic diseases often complicated by increased inflammation. Serum ferritin was found to be an inadequate parameter for assessment and monitoring of iron status. As iron deficiency has been linked with various symptoms, the question arises whether iron supplementation would benefit patients with FID without overt anemia. Future studies should evaluate the role of novel intravenous iron preparations in ameliorating the symptoms of iron deficiency with or without anemia. Disclosures: Klement: Vifor Pharma Ltd: Employment. Cushway:Vifor Pharma Ltd.: Employment.

Download Full-text

The significance of haemochromatosis gene mutations in the general population: implications for screening

Gut ◽

10.1136/gut.43.6.830 ◽

1998 ◽

Vol 43 (6) ◽

pp. 830-836 ◽

Cited By ~ 142

Author(s):

M J Burt ◽

P M George ◽

J D Upton ◽

J A Collett ◽

C M A Frampton ◽

...

Keyword(s):

General Population ◽

Serum Iron ◽

Deoxyribonucleic Acid ◽

Iron Status ◽

Transferrin Saturation ◽

Gene Mutations ◽

The Other ◽

Phenotypic Screening ◽

C282y Mutation ◽

C282y Homozygosity

Background—Haemochromatosis is associated with mutations in the HFE gene but the significance of these mutations in the general population is unknown.Aims—To determine the frequency ofHFE gene mutations in the general population, their effect on serum iron indexes, and their role in screening for haemochromatosis.Methods—Deoxyribonucleic acid (DNA) from 1064 randomly selected subjects was analysed for the C282Y and H63D mutations in the HFE gene. Serum iron, transferrin saturation, and ferritin were measured and individuals with increased iron indexes were investigated to confirm or exclude a clinical diagnosis of haemochromatosis.Results—Mutations were identified in 409 individuals (38.4%) with heterozygote (carrier) frequencies of 13.2% and 24.3% for the C282Y and H63D mutations respectively. Heterozygosity for either mutation significantly increased serum iron and transferrin saturation but despite a similar trend for ferritin, this was only significant for C282Y homozygotes. Five individuals (0.47%) were homozygous for the C282Y mutation, three of whom had haemochromatosis confirmed by liver biopsy (0.28%). The other two C282Y homozygotes would not have been detected by phenotypic screening alone.Conclusions—HFE mutations are present in 38.4% of the population, affect serum iron indexes, and are important determinants of iron status. The population frequency of genetically defined haemochromatosis (C282Y homozygosity) is approximately one in 200 and is higher than the prevalence of clinically apparent haemochromatosis.

Download Full-text

Iron Age or New Age: Ironing out the Diagnosis of Anaemia of Inflammation from Iron Deficiency Anaemia

Blood ◽

10.1182/blood.v126.23.3354.3354 ◽

2015 ◽

Vol 126 (23) ◽

pp. 3354-3354

Author(s):

Nicola J Svenson ◽

Russell Patmore ◽

Heidi J Cox ◽

James R Bailey ◽

Stephen Holding

Keyword(s):

Iron Deficiency ◽

Serum Ferritin ◽

Serum Iron ◽

Iron Status ◽

Diagnostic Testing ◽

Transferrin Saturation ◽

Oral Iron ◽

Gastrointestinal Disorders ◽

Serum Hepcidin ◽

Iron Parameters

Abstract Introduction Iron deficiency anaemia (IDA) and anaemia of chronic inflammation (AI) are the most prevalent causes of iron related anaemia in subjects with gastrointestinal disorders contributing significantly to morbidity and mortality. Diagnosis of IDA and AI is not always straight forward and currently a combination of several serum parameters (ferritin, transferrin, transferrin saturation, iron and C-reactive protein) is required. Subjects with a mixed aetiology can be difficult to interpret using traditional serum parameters, particularly in the presence of an inflammatory process. Hepcidin (a 25 amino-acid peptide hormone) in conjunction with reticulocyte haemoglobin equivalent (RetHe) has the potential to differentiate IDA from AI and in cases of mixed aetiology replacing the traditional laboratory parameters (serum iron, CRP, transferrin saturation and ferritin). Aim The aim of the study was to evaluate the performance of a commercially available ELISA assay and investigate whether hepcidin and RetHe can differentiate AI from mixed aetiology. Method The study investigated 77 patients with gastrointestinal disorders associated with anaemia in a secondary care setting using a traditional pathway of 6 tests (figure 1): Complete Blood Count (CBC), Reticulocytes, serum ferritin, CRP, transferrin, serum Iron. Hepcidin concentration was measured using a commercially available ELISA method (DRG Diagnostic GmbH, Marburg, Germany), CBC and RetHe using a Sysmex XE-2100 CBC analyser, iron parameters and CRP using Beckman Coulter platforms. Results Hepcidin correlated well with ferritin R2 = 0.79, p<0.0001. The results were compared to traditional parameters with Receiver Operator Curves (ROC) used to determine diagnostic cut off concentrations (table 1). Table 1. Sensitivity and specificity of serum ferritin and serum hepcidin used to determine diagnostic cut off values. Selected cut off values IDA AI Serum ferritin 30.0µg/L Sensitivity 83% Specificity 64% Sensitivity 55% Specificity 75% Serum hepcidin 8ng/mL Sensitivity 73% Specificity 72% Sensitivity 70% Specificity 67% Serum hepcidin 40ng/mL Sensitivity 98% Specificity 32% Sensitivity 25% Specificity 91% Ferritin was unable to distinguish IDA from AI in mixed aetiology situations. This gives rise to a new proposed 2 step pathway (figure 2) using 3 tests: CBC, RetHe and hepcidin differentiating IDA from AI in mixed aetiology cases indicating the cause of the anaemia. The RetHe value can then be used to predict the response to oral iron. Conclusion Serum hepcidin may not yet replace serum ferritin as the preferred iron status marker, but in conjunction with RetHe it may distinguish mixed aetiology subjects. This offers the potential development of a clearer clinical pathway for investigation of difficult subjects, including reduction in the number of tests required during anaemia investigations and shorter diagnosis times. The advantage of hepcidin together with RetHe over traditional iron parameters is both as a real time marker of iron status and an indication of likelihood of response to iron therapy. The patient would benefit from a shorter recovery time, unnecessary testing, reduction in ineffective treatment and overall reduction in costs. Figure 1. Current diagnostic testing pathway using 6 independent tests with serum ferritin used as the primary indicator of iron stores. Figure 1. Current diagnostic testing pathway using 6 independent tests with serum ferritin used as the primary indicator of iron stores. Figure 2. Suggestion of a new 2 step diagnostic testing pathway with serum hepcidin as the primary indicator and reticulocyte haemoglobin equivalent as the predictor of iron deficiency and response to oral iron. Figure 2. Suggestion of a new 2 step diagnostic testing pathway with serum hepcidin as the primary indicator and reticulocyte haemoglobin equivalent as the predictor of iron deficiency and response to oral iron. Disclosures Patmore: Janssen: Honoraria; Gilead: Honoraria.

Download Full-text

Correlation between vivax malaria infection and iron deficiency in children

Paediatrica Indonesiana ◽

10.14238/pi55.1.2015.44-9 ◽

2015 ◽

Vol 55 (1) ◽

pp. 44

Author(s):

Desmansyah Desmansyah ◽

Rini Purnamasari ◽

Theodorus Theodorus ◽

Sulaiman Waiman

Keyword(s):

Iron Deficiency ◽

Serum Ferritin ◽

Vivax Malaria ◽

Malaria Infection ◽

Serum Iron ◽

Iron Status ◽

Transferrin Saturation ◽

Hemoglobin Level ◽

Ferritin Concentration ◽

Iron Deficient

Background Iron deficiency is considered to be a major public health problem around the world due to its high prevalence as well as its effect on growth, development, and infection-resistance in children. In malaria-endemic areas, malaria infection is thought to contribute to the occurrence of iron deficiency, by means of hepcidin and hemolysis mechanisms. Objective To assess the prevalence of asymptomatic vivax malaria, compare hemoglobin levels and iron status parameters between vivax malaria-infected and uninfected children, assess the prevalence of iron deficiency, and evaluate a possible correlation between vivax malaria infection and iron deficiency. Methods This cross-sectional study was conducted from February to April 2013 at Sanana City of Sula Islands District, North Maluku. Six parameters were evaluated in 5-11-year-old children: malaria parasite infection, hemoglobin level, serum iron concentration, total iron-binding capacity (TIBC), serum transferrin saturation, and serum ferritin concentration. Results Among 296 children aged 5-11 years, 75 (25.3%) were infected with Plasmodium vivax. In infected children, hemoglobin, serum iron, transferrin saturation, TIBC and serum ferritin were significantly lower than in non-infected children (P<0.01). Using a serum ferritin cut-off of <15 μg/dL, 142 (48.0%) of the children were found to be iron deficient. There was a strong correlation between vivax malaria infection and iron deficiency (OR 3.573; 95%CI 2.03-6.29). ConclusionThe prevalence of asymptomatic vivax malaria infection was 25.3%. The hemoglobin level and iron status parameters in vivax malaria-infected subjects were significantly lower than in uninfected children. The prevalence of iron deficiency was 48.0% for all study subjects. Malaria vivax infection was correlated with iron deficiency in 5-11-year-old children at Sanana City.

Download Full-text

Sex-Specific Genetically Predicted Iron Status in relation to 12 Vascular Diseases: A Mendelian Randomization Study in the UK Biobank

BioMed Research International ◽

10.1155/2020/6246041 ◽

2020 ◽

Vol 2020 ◽

pp. 1-8

Author(s):

Fangkun Yang ◽

Qinyi Bao ◽

Zhuo Wang ◽

Menghuai Ma ◽

Jinlian Shen ◽

...

Keyword(s):

Coronary Atherosclerosis ◽

Serum Iron ◽

Mendelian Randomization ◽

Iron Status ◽

Transferrin Saturation ◽

Vascular Diseases ◽

Lower Extremities ◽

Vascular Pathology ◽

Uk Biobank ◽

The Uk

Background. Iron overload has been implicated in the pathogenesis of varicose veins (VVs). However, the association of serum iron status with other vascular diseases (VDs) is not well understood, which might be a potential target for VD prevention. This study was aimed at investigating the causal associations between iron status and VDs using the Mendelian randomization (MR) method. Methods. A two-sample MR was designed to investigate whether iron status was associated with VDs, based on iron data from a published genome-wide association study meta-analysis of 48,972 subjects of European descent and VD data obtained from the UK Biobank, including 361,194 British subjects (167,020 males and 194,174 females). We further explored whether there was sex difference in the associations between genetically predicted iron status and VDs. Results. The results demonstrated that iron status had a significant causal effect on VVs of lower extremities ( P < 0.001 ) and a potential effect on coronary atherosclerosis ( P < 0.05 for serum iron, ferritin, and transferrin saturation, respectively), but not on other VDs. Furthermore, higher iron status exerted a detrimental effect on VVs of lower extremities in both genders ( P < 0.05 ) and a protective effect on male patients with coronary atherosclerosis ( P < 0.05 for serum iron, ferritin, and transferrin saturation, respectively). Conclusions. This MR study provides robust evidence that higher iron status increases the risk of VVs of lower extremities, whereas it reduces the incidence of coronary atherosclerosis in the male population, which indicates that iron has divergent effects on vascular pathology.

Download Full-text