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

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 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+).

Blood ◽

10.1182/blood.v108.11.3828.3828 ◽

2006 ◽

Vol 108 (11) ◽

pp. 3828-3828

Author(s):

Jose Manuel Calvo-Villas ◽

María Francisca Zapata ◽

Ivan Alvarez ◽

Silvia de la Iglesia ◽

Jorge Cuesta ◽

...

Keyword(s):

Iron Deficiency ◽

Transferrin Receptor ◽

Biochemical Parameters ◽

Iron Status ◽

Direct Sequencing ◽

Saturation Index ◽

Transferrin Saturation ◽

Soluble Transferrin Receptor ◽

Iron Deficient ◽

Significant Difference

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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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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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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Serum ferritin, soluble transferrin receptor, and total body iron for the detection of iron deficiency in early pregnancy: a multiethnic population-based study with low use of iron supplements

American Journal of Clinical Nutrition ◽

10.1093/ajcn/nqy366 ◽

2019 ◽

Vol 109 (3) ◽

pp. 566-575 ◽

Cited By ~ 3

Author(s):

Marthe-Lise Næss-Andresen ◽

Åse Ruth Eggemoen ◽

Jens Petter Berg ◽

Ragnhild Sørum Falk ◽

Anne Karen Jenum

Keyword(s):

Iron Deficiency ◽

South Asian ◽

Transferrin Receptor ◽

Iron Status ◽

Middle Eastern ◽

Population Based ◽

Soluble Transferrin Receptor ◽

Body Iron ◽

Sub Saharan ◽

Total Body

ABSTRACTBackgroundWhich blood-based indicator best reflects the iron status in pregnant women is unclear. Better assessments of iron status in today's multiethnic populations are needed to optimize treatment and clinical recommendations.ObjectivesWe aimed to determine the prevalence of anemia (hemoglobin <11.0 g/dL in first and <10.5 g/dL in second trimester) and iron deficiency (ID) by the iron indicators serum ferritin <15 µg/L, serum soluble transferrin receptor (sTfR) >4.4 mg/L, and calculated total body iron <0 mg/kg, and their associations with ethnicity.MethodsThis was a population-based cross-sectional study from primary antenatal care of 792 healthy women in early pregnancy in Oslo, Norway. We categorized the women into 6 ethnic groups: Western European, South Asian, Middle Eastern, Sub-Saharan African, East Asian, and Eastern European.ResultsAnemia was found in 5.9% of women (Western Europeans: 1.8%; non-Western: 0–14%, P < 0.05). ID from ferritin was found in 33% (Western Europeans: 15%; non-Western: 27–55%, P < 0.05). ID from sTfR was found in 6.5% (Western Europeans: 0.3%; non-Western: 0–20%, P < 0.01). Calculated total body iron indicated ID in 11% (Western Europeans: 0.6%, non-Western: 7.0–28%, P < 0.01). The prevalence of ID was significantly higher by all measures in South Asian, Sub-Saharan African, and Middle Eastern than in Western European women, and the ethnic differences persisted after adjusting for confounders. South Asians, Sub-Saharan Africans, and Middle Easterners had lower iron concentrations by all measures for all hemoglobin intervals. Anemia related to ID varied from 35% (sTfR) to 46% (total body iron) and 72% (ferritin) depending on the iron indicator used.ConclusionsWomen at the highest risk of ID and anemia were of South Asian, Middle Eastern, and Sub-Saharan African origin. The prevalence of ID differed considerably depending on the iron indicator used.

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Effect of Fortification with Multiple Micronutrient Powder on the Prevention and Treatment of Iron Deficiency and Anaemia in Brazilian Children: A Randomized Clinical Trial

Nutrients ◽

10.3390/nu13072160 ◽

2021 ◽

Vol 13 (7) ◽

pp. 2160

Author(s):

Malaine Morais Alves Machado ◽

Mirella de Paiva Lopes ◽

Raquel Machado Schincaglia ◽

Paulo Sérgio Sucasas da Costa ◽

Alexandre Siqueira Guedes Coelho ◽

...

Keyword(s):

Iron Deficiency ◽

Serum Ferritin ◽

Transferrin Receptor ◽

Ferrous Sulfate ◽

Soluble Transferrin Receptor ◽

Standard Drug ◽

Micronutrient Powder ◽

Prevention And Treatment ◽

Multiple Micronutrient ◽

Multiple Micronutrient Powder

Fortification with multiple micronutrient powder has been proposed as a public health intervention able to reduce micronutrient deficiencies in children. Our objective was to compare the effectiveness of fortification with multiple micronutrient powder with drug supplementation in the prevention and treatment of iron deficiency and anaemia. This was a cluster trial with anemic and non-anaemic children between six and 42 months old, in randomization data. Non anaemic children received fortification with multiple micronutrient powder or standard drug supplementation of ferrous sulfate associated with folic acid in a prevention dose. Anaemic children who were randomized to receive multiple micronutrient powder also received the recommended iron complementation for anaemia treatment. A total of 162 children were evaluated. The prevalence of anaemia decreased from 13.58 to 1.85%. Iron deficiency decreased from 21.74% to 7.89% (by serum ferritin) and iron deficiency decreased from 66.81 to 38.27% (by soluble transferrin receptor). No difference was identified between interventions for hemoglobin (p = 0.142), serum ferritin (p = 0.288), and soluble transferrin receptor (p = 0.156). Fortification with multiple micronutrient powder was effective in preventing iron deficiency and anaemia in children aged six to 48 months. In anaemic children; it was necessary to supplement the dose of multiple micronutrient powder with ferrous sulfate.

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Prenatal Iron Deficiency and Replete Iron Status Are Associated with Adverse Birth Outcomes, but Associations Differ in Ghana and Malawi

Journal of Nutrition ◽

10.1093/jn/nxy278 ◽

2019 ◽

Vol 149 (3) ◽

pp. 513-521 ◽

Cited By ~ 1

Author(s):

Brietta M Oaks ◽

Josh M Jorgensen ◽

Lacey M Baldiviez ◽

Seth Adu-Afarwuah ◽

Ken Maleta ◽

...

Keyword(s):

Iron Deficiency ◽

Birth Outcomes ◽

Regression Models ◽

Iron Status ◽

Secondary Data ◽

Hemoglobin Concentration ◽

Late Pregnancy ◽

Zinc Protoporphyrin ◽

Adverse Birth Outcomes ◽

Soluble Transferrin Receptor

ABSTRACTBackgroundPrevious literature suggests a U-shaped relation between hemoglobin concentration and adverse birth outcomes. There is less evidence on associations between iron status and birth outcomes.ObjectiveOur objective was to determine the associations of maternal hemoglobin concentration and iron status with birth outcomes.MethodsWe conducted a secondary data analysis of data from 2 cohorts of pregnant women receiving iron-containing nutritional supplements (20–60 mg ferrous sulfate) in Ghana (n = 1137) and Malawi (n = 1243). Hemoglobin concentration and 2 markers of iron status [zinc protoporphyrin and soluble transferrin receptor (sTfR)] were measured at ≤20 weeks and 36 weeks of gestation. We used linear and Poisson regression models and birth outcomes included preterm birth (PTB), newborn stunting, low birth weight (LBW), and small-for-gestational-age.ResultsPrevalence of iron deficiency (sTfR >6.0 mg/L) at enrollment was 9% in Ghana and 20% in Malawi. In early pregnancy, iron deficiency was associated with PTB (9% compared with 17%, adjusted RR: 1.63; 95% CI: 1.14, 2.33) and stunting (15% compared with 23%, adjusted RR: 1.44; 95% CI: 1.09, 1.94) in Malawi but not Ghana, and was not associated with LBW in either country; replete iron status (sTfR <10th percentile) was associated with stunting (9% compared with 15%, adjusted RR: 1.71; 95% CI: 1.06, 2.77) in Ghana, but not PTB or LBW, and was not associated with any birth outcomes in Malawi. In late pregnancy, iron deficiency was not related to birth outcomes in either country and iron-replete status was associated with higher risk of LBW (8% compared with 16%, adjusted RR: 1.90; 95% CI: 1.17, 3.09) and stunting (6% compared with 13%, adjusted RR: 2.14; 95% CI: 1.21, 3.77) in Ghana, but was not associated with birth outcomes in Malawi.ConclusionsThe associations of low or replete iron status with birth outcomes are population specific. Research to replicate and extend these findings would be beneficial. These trials were registered at clinicaltrials.gov as NCT00970866 (Ghana) and NCT01239693 (Malawi).

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