Serum Soluble Transferrin Receptor in Heterozygous β-Thalassaemia: Application in the Diagnosis of Iron Deficiency and as Hematologic Marker of Erythroid Activity According to Thalassaemic Genotypes (β0 vs β+).

Abstract Although an increased level of serum soluble transferrin receptor (sTfR) have been found in both heterozygous β-thalassaemia patients with iron deficiency and in those with more severe genotype (β0), it is not a useful marker of iron deficiency status associated to β-thalassaemia. The aim of this study was to analyse the use of two biochemical parameters (sTfR and sTfR/log of ferritin ratio) to determine the iron status and to evaluate the degree of erythropoietic activity in a group of 221 β-thalassaemic heterozigotes patients (155 β0 and 66 β+). Serum ferritin and transferrin saturation index were measured in order to establish the iron status. Of the whole group, 51 patients were iron defficient (βthal-ID) while the remaining 170 were iron sufficient (βthal-IS). Based on the combination of β-thalassaemia genotype and iron status, patients were classified into four subgroups: β0thalassaemia and iron-sufficient (β0thal-IS) (n=124); β0thalassaemia and iron-deficient (β0thal-ID) (n=31); β+thalassaemia and iron-sufficient (β+thal-IS) (n=46); β+thalassaemia and iron-deficient (β+thal-ID) (n=20). 258 healthy and 56 iron-deficient individuals were used as controls. All the haematological parameters were measured by using analyzer Coulter® GEN-S™. Haemoglobins A2 (Hb A2) and F (HbF) were analysed by high performance liquid chromatography and molecular analysis was performed by real-time PCR and direct sequencing techniques. Chemical, inmunoturbidimetrical and nephelometric methods were used to measure iron status as well as sTfR. Comparison of haemalogical and biochemical parameters between subgroups was performed by using the t-student test and correlation analysis was calculated by using least-squares regression model. Mean sTfR level obtained was 2.63 ± 0.8 mg/dL and 2.57 ± 1.1 mg/dL in βthal-ID and βthal-IS patients respectively (p=0.783). Soluble transferrin receptor showed a positive correlation with HbA2, HbF and reticulocyte count values in βthal-IS patients (r=0.208 [p<0.05], r=0.440 [p<0.0001] and r=0.393 [p<0.00001] respectively) while it did not reach a significant correlation in βthal-ID patients. Mean sTfR/log sFt ratio was 2.75 ± 1.6 and 1.34 ± 0.5 in βthal-ID and βthal-IS patients (p<0.001). Interestingly, sTfR level was significantly higher in β0thal-IS patients when compared with β+thal-IS patients (2.76 ± 0.9 vs 1.42 ± 0.4) (p<0.001) as a result of an increased globin chains imbalance related to the β0 genotype. In the other hand, in the comparison between β0thal-ID and β+thal-ID subgroups neither sTfr level (2.71 ± 0.7 vs 2.40 ± 1.1) (p=0.417) nor sTfR/log sFt ratio (2.93 ± 1.7 vs 2.24 ± 1.3) (p=0.371) showed significant difference. In summary, sTfR/log sFt ratio is a valid parameter for diagnosis of iron deficiency associated to heterozygous β-thalassaemia. Unlike the findings observed in β-thalassaemic heterozigotes with normal iron status, sTfR level is not useful to evaluate the genotype severity in those with iron deficiency. Consequently, iron status should be determined before using sTfR as a parameter to provide a reliable estimation of the ineffective erythropoiesis related to the severity of β-thalassaemia genotypes.

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Using Soluble Transferrin Receptor and Taking Inflammation into Account When Defining Serum Ferritin Cutoffs Improved the Diagnosis of Iron Deficiency in a Group of Canadian Preschool Inuit Children from Nunavik

Anemia ◽

10.1155/2016/6430214 ◽

2016 ◽

Vol 2016 ◽

pp. 1-10 ◽

Cited By ~ 5

Author(s):

Huguette Turgeon O’Brien ◽

Rosanne Blanchet ◽

Doris Gagné ◽

Julie Lauzière ◽

Carole Vézina

Keyword(s):

Iron Deficiency ◽

Transferrin Receptor ◽

Binding Capacity ◽

Iron Status ◽

Transferrin Saturation ◽

Deficiency Anemia ◽

Soluble Transferrin Receptor ◽

Iron Depletion ◽

Reactive Protein ◽

Iron Deficient

The prevalence of iron depletion, iron deficient erythropoiesis (IDE), and iron deficiency anemia (IDA) was assessed in preschool Inuit children using soluble transferrin receptor (sTfR) and traditional indicators of iron status while disregarding or taking inflammation into account when defining SF cutoffs. Iron depletion was defined as follows: (1) SF < 15 μg/L regardless of the C-reactive protein (CRP) level and (2) SF < 15 or <50 μg/L with CRP ≤ 5 or >5 mg/L, respectively. IDE corresponded to iron depletion combined with total iron binding capacity > 72 μmol/L and/or transferrin saturation < 16%. Iron depletion and IDE affected almost half of the children when accounting for inflammation, compared to one-third when the SF cutoff was defined regardless of CRP level (P<0.0001). The prevalence of IDE adjusted for inflammation (45.1%) was very similar to the prevalence observed when sTfR was used as a sole marker of IDE (47.4%). The prevalence of anemia was 15%. The prevalence of IDA (IDE + hemoglobin < 110 g/L) was higher when accounting for than when disregarding inflammation (8.0% versus 6.2%,P=0.083). Using sTfR and different SF cutoffs for children with versus without inflammation improved the diagnosis of iron depletion and IDE. Our results confirm that Inuit children are at particularly high risk for iron deficiency.

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SOLUBLE TRANSFERRIN RECEPTOR IS A PROMISING MARKER of IRON DEFICIENCY ANEMIA IN PREVALENT HEMODIALYSIS PATIENTS

QJM ◽

10.1093/qjmed/hcab100.090 ◽

2021 ◽

Vol 114 (Supplement_1) ◽

Author(s):

Khaled Abou seif ◽

Hussien Sayed Hussien ◽

Shaimaa Abdelmegied ◽

Marwa Abdulhady

Keyword(s):

Iron Deficiency ◽

Iron Deficiency Anemia ◽

Transferrin Receptor ◽

Iron Status ◽

Hemodialysis Patients ◽

Deficiency Anemia ◽

P Value ◽

Soluble Transferrin Receptor ◽

Significant Difference ◽

And Control

Abstract: Background Diagnosis of iron deficiency is traditionally based on ferritin and other iron parameters becomes difficult in end stage renal disease patients due to the inflammatory condition which affects these markers and masks the iron deficiency. Serum soluble transferrin receptor (sTfR) is able to be a reliable indicator for assessing iron status, as it is not affected by inflammatory procedures. Aim To evaluate the usefulness of serum soluble transferrin receptors in iron deficiency anemia detection in comparison to the classic markers of iron status in prevalent hemodialysis patients. Methods This case-control study assessed sTfR in 80 prevalent ESRD patients on regular hemodialysis in 2 groups. Group A (N = 40): CRP >10 and group B (N = 40):CRP <10 and apparently healthy 8 control subjects. Results The cut of value of STFRs in hemodialysis patients was 12.5 mg\l. The prevalence of STFRs in patients with CRP<10 was 85%, while in patients with CRP>10 was 92.5% (P-value 0.288). STFRs have high sensitivity 88.75, specificity 100, PPV100% and NPV 47.1%. The hemodialysis patients who have elevated STFRs have risk 1.22 times to have iron deficiency anemia if CRP <10 (odds ratio: 1.22) and 3.14 times if CRP>10 (odds ratio: 3.14). There was significant difference on comparing patients with CRP<10, CRP>10 and control as regard Hb and STFR with P-value 0.0001 and 0.0001 respectively. Post Hoc analysis showed significant difference in both between the patients with CRP<10 and control also in patients with CRP>10 and control (p value <0.0001). while on comparing patients with CRP<10 with patients with CRP>10 there was significant difference in STFRs p value 0.0001 despite no significant difference in hemoglobin (p value 0.642) and classic marker of iron deficiency (s.iron, TIBC, TSAT) with p value 0.701,0.192,0.382 respectively. Serum STFRs was negatively correlated with s.iron and Kt\v (r -0.372, P-value 0.018) and (r-0.416, p value 0.008) respectively in patients with CRP <10. Conclusion Serum soluble transferrin receptor is highly sensitive and specific marker for iron deficiency in hemodialysis patients especially in patients with high CRP level.

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Deranged Iron Status Evidenced by Iron Deficiency Characterizes Patients with Hidradenitis Suppurativa

Dermatology ◽

10.1159/000505184 ◽

2020 ◽

Vol 236 (1) ◽

pp. 52-58

Author(s):

Malgorzata Ponikowska ◽

Lukasz Matusiak ◽

Monika Kasztura ◽

Ewa A. Jankowska ◽

Jacek C. Szepietowski

Keyword(s):

Iron Deficiency ◽

Disease Severity ◽

Transferrin Receptor ◽

Hidradenitis Suppurativa ◽

Iron Status ◽

Transferrin Saturation ◽

Severity Index ◽

Soluble Transferrin Receptor ◽

Serum Concentrations ◽

Autoimmune Processes

Background: Proinflammatory activation and autoimmune processes underlie the pathophysiology of hidradenitis suppurativa (HS). Iron deficiency (ID) is frequently present in inflammation-mediated chronic diseases, irrespective of anemia. Objectives: We aimed to characterize iron status in patients with HS. Methods: Serum concentrations of ferritin, transferrin saturation (Tsat), soluble transferrin receptor and hepcidin were assessed as the biomarkers of iron status in 74 patients with HS and 44 healthy subjects. ID was defined as ferritin <100 µg/L or ferritin 100–299 µg/L with Tsat <20% (following the definition used in the other studies in chronic disease). Results: Compared with controls, patients with HS demonstrated a deranged iron status as evidenced by decreased levels of ferritin (91 ± 87 vs. 157 ± 99 µg/L), Tsat (21.5 ± 10.8 vs. 42.2 ± 11.7%) and hepcidin (31.3 ± 25.9 vs. 44.2 ± 22.0 ng/mL) (all p < 0.05 vs. controls). There was also a trend toward higher values of soluble transferrin receptor (1.23 ± 0.35 vs. 1.12 ± 0.19 mg/L) (p = 0.09 vs. controls). Disease severity (assessed with the Hidradenitis Suppurativa Severity Index and the 3-degree Hurley scale) did not differentiate iron status biomarkers. ID was present in 75% of HS patients, and its prevalence was not related with disease severity (Hurley I/II/III – 82 vs. 73 vs. 67%). In HS, none of the iron status biomarkers correlated with the levels of interleukin-6 (a marker of proinflammatory activation). Conclusions: The majority of HS patients demonstrate derangements in iron status typical of ID. These abnormalities are neither related to proinflammatory activation nor associated with disease severity. Whether it may have a therapeutic impact needs to be further studied.

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Increased Serum Transferrin Saturation Is Associated with Lower Serum Transferrin Receptor Concentration

Clinical Chemistry ◽

10.1093/clinchem/45.12.2191 ◽

1999 ◽

Vol 45 (12) ◽

pp. 2191-2199 ◽

Cited By ~ 16

Author(s):

Anne C Looker ◽

Mark Loyevsky ◽

Victor R Gordeuk

Keyword(s):

Iron Deficiency ◽

Iron Overload ◽

Transferrin Receptor ◽

Iron Status ◽

Transferrin Saturation ◽

Reference Interval ◽

Serum Transferrin ◽

Reactive Protein ◽

Serum Transferrin Receptor ◽

Health And Nutrition

Abstract Background: Serum transferrin receptor (sTfR) concentrations are increased in iron deficiency. We wished to examine whether they are decreased in the presence of potential iron-loading conditions, as reflected by increased transferrin saturation (TS) on a single occasion. Methods: We compared sTfR concentrations between 570 controls with normal iron status and 189 cases with increased serum TS on a single occasion; these latter individuals may be potential cases of iron overload. Cases and controls were selected from adults who had been examined in the third National Health and Nutrition Examination Survey (1988–1994) and for whom excess sera were available to perform sTfR measurements after the survey’s completion. Increased TS was defined as >60% for men and >55% for women; normal iron status was defined as having no evidence of iron deficiency, iron overload, or inflammation indicated by serum ferritin, TS, erythrocyte protoporphyrin, and C-reactive protein. Results: Mean sTfR and mean log sTfR:ferritin were ∼10% and 24% lower, respectively, in cases than in controls (P <0.002). Cases were significantly more likely to have an sTfR value <2.9 mg/L, the lower limit of the reference interval, than were controls (odds ratio = 1.8; 95% confidence interval, 1.04–2.37). Conclusion: Our results support previous studies that suggested that sTfR may be useful for assessing high iron status in populations.

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Impact of Iron Status on Thyroid Function: A Community Based Cross-Sectional Study in Eastern Nepal

Journal of College of Medical Sciences-Nepal ◽

10.3126/jcmsn.v15i1.21022 ◽

2019 ◽

Vol 15 (1) ◽

pp. 18-21 ◽

Cited By ~ 1

Author(s):

Saroj Thapa ◽

Madhab Lamsal ◽

Sanjay Kumar Sah ◽

Rajendra Kumar Chaudhari ◽

Basanta Gelal ◽

...

Keyword(s):

Iron Deficiency ◽

Iron Status ◽

Transferrin Saturation ◽

Cross Sectional Study ◽

Sectional Study ◽

Community Based ◽

Cross Sectional ◽

Hormone Profile ◽

Iron Deficient ◽

The Mean

Background: Iron deficiency is the most common nutritional deficiency in the world. The relation between thyroid hormones and iron status is bidirectional. The aim of this study was to assess iron nutrition status and evaluate its relationship with thyroid hormone profile among children of Eastern Nepal. Methods: A community based cross-sectional study was conducted in eastern Nepal. A total of 200 school children aged 6-12 years were recruited after taking informed consent from their guardians. Blood samples were collected and assayed for free thyroid hormones (fT3 and fT4), thyroid stimulating hormone (TSH), serum iron, total iron binding capacity (TIBC) concentration and percentage transferrin saturation was calculated. Results: The mean serum iron and TIBC was 74.04 µg/dl and 389.38 µg/dl respectively. The median transferring saturation was 19.21%. The overall prevalence of iron deficiency (Transferrin saturation < 16%) was 34% (n=68). The mean concentration of fT3 and fT4 was 2.87 pg/ml and 1.21 ng/dl respectively, while the median TSH concentration was 3.03 mIU/L. Median TSH concentration in iron deficient group (3.11 µg/dl) and iron sufficient group (2.91 µg/dl) was not significantly different. Among iron deficient children 5.9% had subclinical hypothyroidism (n=4). Iron status indicators were not significantly correlated with thyroid profile parameters in the study population. Conclusions: The prevalence of iron deficiency is high and iron deficiency does not significantly alter the thyroid hormone profile in the study region.

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Evaluation of the iron status of a population

Blood ◽

10.1182/blood.v48.3.449.449 ◽

1976 ◽

Vol 48 (3) ◽

pp. 449-455 ◽

Cited By ~ 293

Author(s):

JD Cook ◽

CA Finch ◽

NJ Smith

Keyword(s):

Iron Deficiency ◽

Serum Ferritin ◽

Iron Status ◽

Transferrin Saturation ◽

Red Cell ◽

Adult Males ◽

Packed Red Blood Cells ◽

Iron Deficient ◽

Menstruating Women ◽

Prevalence Of Anemia

Abstract The iron status of a population of 1564 subjects living in the northwestern United States was evaluated by measurements of transferrin saturation, red cell protoporphyrin, and serum ferritin. The frequency distribution of these parameters showed no distinct separation between normal and iron-deficient subjects. When only one of these three parameters was abnormal (transferrin saturation below 15%, red cell protoporphyrin above 100 mug/ml packed red blood cells, serum ferritin below 12 ng/ml), the prevalence of anemia was only slightly greater (10.9%) than in the entire sample (8.3%). The prevalence of anemia was increased to 28% in individuals with two or more abnormal parameters, and to 63% when all three parameters were abnormal. As defined by the presence of at least two abnormal parameters, the prevalence of iron deficiency in various populations separated on the basis of age and sex ranged from 3% in adolescent and adult males to 20% in menstruating women. It is concluded that the accuracy of detecting iron deficiency in population surveys can be substantially improved by employing a battery of laboratory measurements of the iron status.

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Evaluation of new immunoenzymometric assay for measuring soluble transferrin receptor to detect iron deficiency in anemic patients

Clinical Chemistry ◽

10.1093/clinchem/43.9.1641 ◽

1997 ◽

Vol 43 (9) ◽

pp. 1641-1646 ◽

Cited By ~ 66

Author(s):

Pauli Suominen ◽

Kari Punnonen ◽

Allan Rajamäki ◽

Kerttu Irjala

Keyword(s):

Iron Deficiency ◽

Transferrin Receptor ◽

Bone Marrow Aspirate ◽

Clinical Performance ◽

Iron Status ◽

Clinical Work ◽

Analytical Performance ◽

Soluble Transferrin Receptor ◽

Commercial Test ◽

Clinical Applicability

Abstract During the last few years the measurement of serum-soluble transferrin receptor (sTfR) has been introduced as a tool to detect iron deficiency and as an analyte to differentiate between anemia caused by iron deficiency (IDA) and that caused by chronic disease (ACD). Commercially available methods have emerged to make diagnostics by sTfR more readily accessible. We documented the analytical performance of a newly introduced IDeATM sTfR immunoenzymometric assay (IEMA) by Orion Diagnostica. We also evaluated its clinical performance in 98 consecutive anemic patients, with information derived from bone marrow aspirate samples as the reference for iron status. The clinical usefulness of two other commercially available sTfR assays was assessed for comparison. The analytical performance and clinical applicability of the IDeA were sufficient to support reliable clinical work. We conclude that IDA and iron deficiency in the presence of inflammatory states can be differentiated efficiently from ACD with this new commercial test to measure sTfR.

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Serum Transferrin Receptor and Transferrin Receptor-Ferritin Index Identify Healthy Subjects With Subclinical Iron Deficits

Blood ◽

10.1182/blood.v92.8.2934.420k07_2934_2939 ◽

1998 ◽

Vol 92 (8) ◽

pp. 2934-2939 ◽

Cited By ~ 1

Author(s):

Pauli Suominen ◽

Kari Punnonen ◽

Allan Rajamäki ◽

Kerttu Irjala

Keyword(s):

Iron Deficiency ◽

Transferrin Receptor ◽

Iron Supplementation ◽

Iron Status ◽

Serum Transferrin ◽

Serum Transferrin Receptor ◽

Iron Deficient ◽

American Society ◽

Induced Changes ◽

Apparently Healthy

Despite the established utility of serum transferrin receptor (sTfR), serum ferritin, and the sTfR/log ferritin ratio (TfR-F Index) in the diagnosis of iron deficiency (ID) anemia, the numeric values of these parameters, which are indicative of subclinical ID, remain to be clearly defined. In this study, 65 apparently healthy nonanemic adults (22 men and 43 women) were treated with 3 months of oral iron supplementation to evaluate its effect on parameters reflecting iron status and to determine the prevalence of subclinical iron deficiency in apparently healthy adults. Significant supplementation-induced changes were observed in sTfR, ferritin, and TfR-F Index values in women, whereas in men, none of the studied parameters showed any significant change. Iron-deficient erythropoiesis (IDE) was not observed in men, but was found in 17 women (40%). Although individuals with a compromised iron status may be represented in substantial numbers in conventional reference populations, they can be readily identified using sTfR, ferritin, and TfR-F Index determinations. © 1998 by The American Society of Hematology.

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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.

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Soluble transferrin receptor as an indicator of iron deficiency and febrile seizures

Paediatrica Indonesiana ◽

10.14238/pi55.2.2015.95-100 ◽

2015 ◽

Vol 55 (2) ◽

pp. 95

Author(s):

Salma Salma ◽

Rita Arifin ◽

Erial Bahar ◽

Rini Purnamasari

Keyword(s):

Risk Factors ◽

Risk Factor ◽

Iron Deficiency ◽

Transferrin Receptor ◽

Febrile Seizures ◽

Control Group ◽

Soluble Transferrin Receptor ◽

Iron Deficient ◽

High Incidence ◽

Matched Case

Background Iron deficiency (ID) has a high incidence inIndonesia, and is a risk factor for febrile seizures. The most suitableassay to detect iron deficiency in the presence of inflammationhas not yet been defined. An indicator of ID unaffected byinflammation is needed, soluble transferrin receptor (sTfR) maybe such an indicator.Objective To evaluate ID as a risk factor for febrile seizures inchildren with inflammation by sTfR measurements.Method We conducted an age-matched, case-control study,focused on children experiencing on acute illnesses at the time.Subjects were 80 children matched by age (40 in the case groupwith febrile seizures, and 40 in the control group who were febrilewithout seizures) aged 3 months to 5 years in Mohammad HoesinHospital, Palembang from February to August 2013. Subjects’clinical data and sTfR levels were recorded. Risk factors wereanalyzed with odd ratios and 95% confident intervals. ThesTfR level cut-off point as a predictor of febrile seizures was alsodefined. Other risk factors were analyzed with multivariate logisticregression test.Results Mean sTfR levels were 41.36 (SD 2.04) nmol/L in thecase group and 33.09 (SD 1.02) nmol/L in the control group.Multivariate analysis revealed ID and iron deficient anemia(IDA), as measured by sTfR levels, to be risk factors for febrileseizures (adjusted OR=3.9; 95%CI 1.41 to 10.8; P=0.007 andOR 3.27; 95%CI 1.21 to 8.84; P=0.017, respectively). The sTfRlevel cut-off point that could be used as a predictor of febrileseizures was 37nmol/L.Conclusion Iron deficiency as measured by increased sTfR isa risk factor for febrile seizures in children.

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