Serum transferrin receptor

Transferrin receptors (TfRs) are the conventional pathway by which cells acquire iron for physiological requirements. Under iron-deficient conditions there is an increased concentration of surface TfR, especially on bone marrow erythroid precursors, as a mechanism to sequester needed iron. TfRs are also present in the circulation, and the circulating serum TfR (sTfR) level reflects total body TfR concentration. Under normal conditions erythroid precursors are the main source of sTfR. Disorders of the bone marrow with reduced erythroid precursors are associated with low sTfR levels. The sTfR concentration begins to rise early in iron deficiency with the onset of iron-deficient erythropoiesis, and continues to rise as iron-deficient erythropoiesis progressively worsens, prior to the development of anemia. The sTfR level does not increase in anemia of chronic inflammation, but is increased when anemia of chronic inflammation is combined with iron deficiency. The sTfR level is also increased in patients with expanded erythropoiesis, including hemolytic anemias, myelodysplastic syndromes, and use of erythropoietic stimulating agents. The ratio of sTfR/ferritin can be used to quantify the entire spectrum of iron status from positive iron stores through negative iron balance, and is particularly useful in evaluating iron status in population studies. The sTfR/log ferritin ratio is valuable for distinguishing anemia of chronic inflammation from iron deficiency anemia, whether the latter occurs alone or in combination with anemia of chronic inflammation.     

Value of Soluble Transferrin Receptors and sTfR/log Ferritin in the Diagnosis of Iron Deficiency Accompanied by Acute Infection

There are many causes of anemia; the most common of these are acute and chronic infections, iron deficiency, or both. Identifying the cause is a very important step in management of anemia. So, we evaluated the usefulness of soluble transferrin receptor (sTfR) and of the sTfR/log ferritin in the diagnosis of iron deficiency anemia accompanied by acute infection. This study was conducted on 131 children aged 2–11 years old from those who attended the pediatric outpatient clinics in Menoufia university hospital. Hematological indices, iron balance and sTfR were evaluated and the sTfR/log F was calculated for each examined child. From the examined children four groups were distinguished: Group I (control): included 34 healthy children with normal iron status (66.7% males, age 4.2 ± 1.2). Group II (IDA): included 38 children diagnosed as iron deficiency anemia (47.4% males, age 4.9 ± 1.6). Group III (IDA + infection): included 26 children with infectious disease (upper respiratory tract infection, otitis media, pneumonia, stomatitis, and urinary tract infection) and anemia meeting criteria of IDA (50% males, age 4.2 ± 0.7). Group IV (anemia + infection): included 33 children with infectious anemia without iron deficiency (56.2% males, age 5.06 ± 1.4). It was proved that sTfR and sTfR/log Ferritin were significantly higher in children with anemia due to iron deficiency, and in those with infection + iron deficiency, versus those with infectious anemia or in healthy children. The use of sTfR and sTfR/log ferritin improves the diagnosis of IDA in pediatric patients, especially in the presence of coexisting acute infection.     

Factor V Leiden mutation carriership and venous thromboembolism in polycythemia vera and essential thrombocythemia

The aim of the present study is to evaluate in an elderly hospitalized population the diagnostic value of the serum transferrin receptor (sTfR) in distinguishing IDA (iron deficiency anemia) from ACD (anemia of chronic disease) as compared to conventional laboratory tests of iron metabolism, especially serum ferritin. In a prospective study, 34 patients with IDA and 38 patients with ACD (a chronic disorder in 23 and an acute infection in 15) were evaluated using iron status tests including serum transferrin receptor assay. The iron stores were assessed by bone marrow examination. sTfR levels were elevated (>28.1 nmol/L) in 68% of the IDA patients but also in 43% of the patients with ACD-chronic inflammation and 33% with ACD-acute infection. Serum ferritin was the best test to differentiate IDA from ACD patients. We conclude that serum ferritin is a more sensitive and specific parameter than the sTfR assay to predict the bone marrow iron status in an elderly anemic population.     

Reference limits and behaviour of serum transferrin receptor in children 6-10 years of age

Serum transferrin receptor (sTfR) originates mostly from erythroblasts and lesser from reticulocytes. The usefulness of sTfR has been implicated in several clinical situations, mainly as a marker of accelerated erythropoiesis or iron deficiency. The assessment of sTfR may be useful in the period of rapid growth during infancy, childhood and adolescence. We evaluated sTfR and the other quantitative and qualitative parameters of the erythropoiesis (Hb, MCV, CHr, Ret-He) and of the iron storage (serum ferritin, sTfR/ferritin index) in a total of 916 children aged 6-10 years. Children were divided into three groups: (A) healthy children, (B) with storage iron deficiency (serum ferritin < 12 microg/l) and (C) Beta trait carriers (HbA2 > 3.3). We determined reference intervals by sex and by age in healthy children. sTfR showed a slight but statistically significant age related increase but did not show significant sex differences. We compared sTfR and the other parameters investigated in the three groups of children. sTfR is not a decisive parameter that can be utilized alone in discriminating the border-line situations between normal and pathologic ones but can help in completing the panel of tests in iron deficiency and in thalassaemia Beta trait carriers.     

The usefulness of serum transferrin receptor and ferritin for assessing anemia in rheumatoid arthritis: comparison with bone marrow iron study

OBJECTIVES: This study was aimed at investigating the usefulness of serum transferrin receptor (sTfR) and ferritin in anemic patients with rheumatoid arthritis (RA) compared with bone marrow storage iron and other tests for anemia. METHODS: Fifty-five anemic RA patients underwent anemia study. Bone marrow iron stain was performed in 18 patients. sTfR and serum ferritin levels were compared with bone marrow iron stores. RESULTS: (1) Mean sTfR concentration was 2.63+/-1.91 mg/L, (2) sTfR correlated with most indicators of anemia, (3) sTfR showed no correlation with CRP and ESR, whereas ferritin did, and (4) sTfR was higher in the "iron depleted" subgroup than in the "iron nondepleted" subgroup in bone marrow study. CONCLUSION: The measurement of sTfR and ferritin is useful in finding the cause of anemia in RA and is a possible substitute for invasive bone marrow iron study.     

Single values of serum transferrin receptor and transferrin receptor ferritin index can be used to detect true and functional iron deficiency in rheumatoid arthritis patients with anemia

OBJECTIVE: To elucidate the use of serum transferrin receptor (sTfR) to distinguish between iron-deficiency anemia (IDA) and anemia of chronic disease (ACD), and to establish an improved scheme to identify functional iron deficiency (FID) in rheumatoid arthritis (RA) patients with anemia. METHODS: We studied 30 anemic RA patients whose iron status was confirmed by bone marrow examination and determination of the sTfR level, serum ferritin level, and sTfR-log ferritin index (TfR-F Index). All patients with diminished or exhausted iron stores (n = 18) received oral iron supplementation. RESULTS: Baseline values of sTfR and the TfR-F Index predicted the response correctly in all patients who received supplementation treatment and were normal in 10 of 11 patients with normal initial iron stores (ACD). CONCLUSION: The results of this study elucidate the roles of sTfR and the TfR-F Index in the differential diagnosis between IDA and ACD and provide direct evidence that these parameters are useful in detecting FID, irrespective of the concurrent iron storage status.     

贫血患者血清转铁蛋白受体测定的临床意义

采用Ｄｏｔ－ＥＬＩＳＡ法定量测定了６８例不同贫血患者的血清转铁蛋白受体（ｓＴＩＲ）水平,发现缺铁性贫血,溶血性贫血和急性失血性贫血患者ｓＴＩＲ均显高于正常人（Ｐ〈０．００１）,而慢性再生障碍性贫血患者ｓＴｆＲ显著低于正常人（Ｐ〈０．００１）,缺铁性贫血ｓＴｆＲ水平与血清铁蛋白水平呈负相关（Ｐ〈０．００５）,溶血性贫血ｓＴｆＲ与网织红细胞计数呈正相关（Ｐ〈０．００５）,ｓＴｆＲ可以反映机体贮存铁和骨     

Serum ferritin in evaluation of iron status in children

The value of serum ferritin in assessing iron status was studied in 192 preschool age children between the ages of 3 and 60 months. Children were considered to have iron deficiency if the transferrin saturation was less than 16% and the peripheral smear revealed microcytosis and hypochromia. Anemia was present when hemoglobin level was 10.5 g/dl. According to this criteria, 46% of children screened had either iron deficiency (11.5%) or iron deficiency anemia (34.4%). Mean serum ferritin for the iron deficiency anemia group was 39.1 ng/mg as compared to 41.7 ng/ml for the iron deficiency group and 84.7 ng/ml for the normal group. Even though the serum ferritin level was lower in the iron deficiency group, the difference in the means did not reach statistical significance. Furthermore, only 30% of children who had either iron deficiency or iron deficiency anemia had serum ferritin level of less than 12 ng/ml, the level considered diagnostic for iron deficiency. It can be concluded that serum ferritin cannot be used alone for iron status determination. Multiple parameters will make the assessment more reliable.     

Serum transferrin receptor levels in patients undergoing evaluation of iron stores: correlation with other parameters and observed versus predicted results

Serum transferrin receptor (sTfR) concentrations were measured in specimens from 77 patients undergoing serum ferritin determination, and the results correlated with serum ferritin, serum iron, serum total iron-binding capacity (TIBC) saturation, erythrocyte mean corpuscular volume (MCV), and mean corpuscular haemoglobin (MCH). All parameters exhibited the expected inverse correlation with sTfR; this correlation was statistically significant for all parameters except serum iron concentration. The frequency with which iron deficiency (defined as absence of stainable marrow iron) is observed in patients with particular ferritin values in this centre was determined and used to estimate the expected number of iron deficient patients in the present study. In no setting were significantly fewer sTfR levels > 3.05 μg/ml observed than expected. However, significantly greater than expected numbers of elevated sTfR values were observed in patients with serum ferritin > 220 μg/l (P = 0.002). The results suggest that the sTfR level is probably not useful as a single test for identification of iron deficiency in unselected patients.     

血清转铁蛋白受体对贫血患者鉴别诊断的临床意义

目的比较各项铁指标在慢性病贫血(ACD),缺铁性贫血(IDA)及ACD合并IDA中的变化规律,明确血清转铁蛋白受体(sTfR)的临床意义.方法设健康志愿者28例为对照组,同时设IDA组29例,ACD组 56例,分别进行血清铁(SI)、总铁结合力(TIBC)、运铁蛋白饱和度(TS)、血清铁蛋白(SF)及sTfR检测,并对26例慢性病患者做骨髓铁染色,根据sTfR值将ACD组分为(1)sTfR值正常组(ACD1组)27例(sTfR≤20.0 nmol/L ),(2)sTfR值升高组(ACD2组)29例(sTfR>20.0 nmol/L).结果 IDA组与其他各组相比,其中平均红细胞体积(68.0±11.3)fl为最小;SI、TS及SF值分别是(19.6±10.1) mg/L、(5.5±2.3)%和(4.3±2.8)μg/L,与对照组(81.7±30.6) mg/L、(27.0±12.0)%和(43.3±26.8) μg/L相比水平明显下降(P≤0.01);sTfR水平(67.2±40.3) nmol/L明显高于对照组(15.6±4.1) nmol/L,P≤0.01.ACD1组SF值(627.3±40.3) μg/L,明显高于其他各组(P≤0.01); SI(60.7±28.7) mg/L和TS(21.1±9.8)%与对照组差异无显著性(P>0.05),10例骨髓铁染色均无缺铁.ACD2组SF值(320.5±156.0) μg/L,高于对照组而低于ACD1组(P≤0.01),16例骨髓铁染色中14例显示铁缺乏,占88%.结论 sTfR值的升高有效地反映了体内铁缺乏状况,是诊断IDA更为敏感的指标,并且较少受慢性炎症性疾病的影响,可与ACD有效鉴别.     

Serum transferrin receptor levels are increased in asymptomatic and mild Plasmodium falciparum-infection.

BACKGROUND AND OBJECTIVE: The serum transferrin receptor (sTfR) concentration in an individual reflects the extent of erythropoietic activity and is considered a useful marker of iron deficiency independent of concurrent inflammation or infection. However, data on the impact of malaria on this parameter are ambiguous. We have examined potential associations of asymptomatic and mild Plasmodium falciparum-infections and of several erythrocyte variants with sTfR values in South West Nigeria. DESIGN AND METHODS: In a cross-sectional study among 161 non-hospitalized children, sTfR concentrations and P. falciparum parasitemia were assessed. In addition, hemoglobin (Hb) and serum ferritin values, Hb-types, glucose-6-phosphate dehydrogenase (G6PD)deficiency and a-globin genotypes were determined and the effects of these factors on sTfR levels were analyzed by univariate and multivariate statistical methods. RESULTS: P. falciparum-infection was present in 77% of the children. Mean sTfR levels were higher in infected than in non-infected children (geometric mean, 3.68, 95% confidence interval [3.5-3.9] vs. 2.99 [2.7-3.3] mg/L; p = 0.0009). There was a significant trend for higher sTfR values with increasing parasite density. sTfR values decreased continuously with age. Hb-types, G6PD-, and a-globin genotypes did not correlate with sTfR levels. In the multivariate analysis, age, Hb and log ferritin values, and parasite density of P. falciparum were independently associated with log sTfR values. INTERPRETATION AND CONCLUSIONS: sTfR concentrations are increased in asymptomatic and mild P. falciparum-infections suggesting adequate bone marrow response in this condition. The diagnostic value of sTfR levels for iron deficiency may be impaired in areas where stable malaria occurs.     

Serum soluble transferrin receptor and the prediction of marrow aspirate iron results in a heterogeneous group of patients.

Serum soluble transferrin receptor (sTfR) concentration has been evaluated in the diagnosis of iron deficiency in otherwise healthy individuals and in patients with rheumatoid arthritis, but has not been studied in a general population of patients with complicated clinical presentations. In this study, 145 anaemic patients with a variety of medical conditions undergoing diagnostic bone marrow aspiration for any reason were tested by a complete blood count, a panel of biochemical tests to evaluate iron status, bone-marrow aspirate iron stain, and serum sTfR concentration. Sixteen per cent lacked stainable iron in the marrow aspirate. All biochemical parameters differed significantly between patients with or without stainable marrow iron. The sTfR assay was significantly more sensitive but less specific than other iron status assays in identifying the absence of stainable iron. Logistic regression analysis demonstrated that only sTfR and ferritin contributed independently to the prediction of marrow iron status. Serum ferritin alone was highly specific but insensitive. A decision algorithm combining serum ferritin and sTfR was as sensitive as TfR and as specific as serum ferritin. The measurement of serum sTfR, especially in conjunction with serum ferritin, is a valuable addition to the existing methods for predicting the results of marrow aspirate iron stains.     

Improved differential diagnosis of anemia of chronic disease and iron deficiency anemia: a prospective multicenter evaluation of soluble transferrin receptor and the sTfR/log ferritin index

Anemia of chronic disease (ACD) and iron deficiency anemia (IDA) are the most prevalent forms of anemia and often occur concurrently. Standard tests of iron status used in differential diagnosis are affected by inflammation, hindering clinical interpretation. In contrast, soluble transferrin receptor (sTfR) indicates iron deficiency and is unaffected by inflammation. Objectives of this prospective multicenter clinical trial were to evaluate and compare the diagnostic accuracy of sTfR and the sTfR/log ferritin index (sTfR Index) for differential diagnosis using the automated Access® sTfR assay (Beckman Coulter) and sTfR Index. We consecutively enrolled 145 anemic patients with common disorders associated with IDA and ACD. Subjects with IDA or ACD + IDA had significantly higher sTfR and sTfR Index values than subjects with ACD (P < 0.0001). ROC curves produced the following cutoffs for sTfR: 21 nmol/L (or 1.55 mg/L), and the sTfR Index: 14 (using nmol/L) (or 1.03 using mg/L). The sTfR Index was superior to sTfR (AUC 0.87 vs. 0.74, P < 0.0001). Use of all three parameters in combination more than doubled the detection of IDA, from 41% (ferritin alone) to 92% (ferritin, sTfR, sTfR Index). Use of sTfR and the sTfR Index improves detection of IDA, particularly in situations where routine markers provide equivocal results. Findings demonstrate a significant advantage in the simultaneous determination of ferritin, sTfR and sTfR Index. Obtaining a ferritin level alone may delay diagnosis of combined IDA and ACD. Am. J. Hematol., 2011. © 2011 Wiley‐Liss, Inc.     

Effect of malaria on soluble transferrin receptor levels in Tanzanian infants

The diagnosis of iron deficiency anemia in malaria endemic areas is complicated by the influence of the infection on the laboratory tests conventionally used to assess iron status. Determination of soluble transferrin receptor (sTfR) levels has been shown to be a sensitive indicator of iron deficiency in adults and is not affected by a range of infectious and inflammatory conditions. The utility of sTfR levels in the diagnosis of iron deficiency in malaria endemic areas remains unresolved. Three hundred and fourteen infants in a rural area of southern Tanzania living under conditions of intense and perennial malaria transmission were studied to determine the utility of sTfR plasma levels in the assessment of iron deficiency anemia. Independent of the presence of anemia, malaria parasitemia was associated with a significant increase in sTfR plasma levels that were even higher than those found in iron deficiency anemia. We conclude that the measurement of sTfR levels does not have a role in the diagnosis of iron deficiency anemia in young children exposed to malaria infection.     

Serum soluble transferrin receptor in the diagnosis of iron deficiency in chronic liver disease

Fifty-one consecutive patients with chronic liver disease (CLD) underwent investigations of their iron status (full blood count, serum iron [Fe], total iron binding capacity [TIBC], transferrin saturation [TS], serum ferritin and serum soluble transferrin receptor [sTfR] level). Twenty-six patients were anaemic; 12 patients had iron deficiency, and 10 had iron deficiency anaemia (IDA). The median (range) sTfR in the IDA patients was 16.6 (11.2–24.8) mg/l, compared with 6.6 mg/l (11.2–24.8) in the 16 patients with anaemia due to other causes (P = 0.01). The sensitivity of sTfR for diagnosing iron deficiency in CLD was 91.6% (100% if only anaemic patients are included) and the specificity was 84.6%. Patients with haemolysis and recent blood loss may have falsely elevated sTfR levels. The results suggest that the sTfR is as useful as serum ferritin in identifying a potentially treatable cause of anaemia in CLD.     

Serum soluble transferrin receptor and the prediction of marrow aspirate iron results in a heterogeneous group of patients

Serum soluble transferrin receptor (sTfR) concentration has been evaluated in the diagnosis of iron deficiency in otherwise healthy individuals and in patients with rheumatoid arthritis, but has not been studied in a general population of patients with complicated clinical presentations. In this study, 145 anaemic patients with a variety of medical conditions undergoing diagnostic bone marrow aspiration for any reason were tested by a complete blood count, a panel of biochemical tests to evaluate iron status, bone-marrow aspirate iron stain, and serum sTfR concentration. Sixteen per cent lacked stainable iron in the marrow aspirate. All biochemical parameters differed significantly between patients with or without stainable marrow iron. The sTfR assay was significantly more sensitive but less specific than other iron status assays in identifying the absence of stainable iron. Logistic regression analysis demonstrated that only sTfR and ferritin contributed independently to the prediction of marrow iron status. Serum ferritin alone was highly specific but insensitive. A decision algorithm combining serum ferritin and sTfR was as sensitive as TfR and as specific as serum ferritin. The measurement of serum sTfR, especially in conjunction with serum ferritin, is a valuable addition to the existing methods for predicting the results of marrow aspirate iron stains.     

Reduced soluble transferrin receptor concentrations in acute malaria in Vanuatu.

Soluble transferrin receptor (sTfR) concentration is a sensitive index of iron deficiency when used in conjunction with ferritin measurements in adults. One advantage of this assay is that unlike ferritin it does not appear to be affected by a range of infectious and inflammatory conditions or by pregnancy, rendering it a promising adjunct to the diagnosis of iron deficiency in tropical populations. We have measured plasma sTfR concentrations in a group of malaria patients (n = 21) and asymptomatic (18) and aparasitemic (76) controls in Vanuatu. Plasma sTfR concentration was significantly reduced in individuals with acute malaria (P = 0.003). While this observation provides evidence that erythropoeitic suppression may be an important etiologic component in malarial anemia, it also suggests that malaria may be a confounding factor when interpreting sTfR concentrations in such populations. The role of sTfR in the diagnosis of iron deficiency in tropical populations remains to be established.     

Serum soluble transferrin receptor in the diagnosis of iron deficiency in chronic liver disease.

Fifty-one consecutive patients with chronic liver disease (CLD) underwent investigations of their iron status (full blood count, serum iron [Fe], total iron binding capacity [TIBC], transferrin saturation [TS], serum ferritin and serum soluble transferrin receptor [sTfR] level). Twenty-six patients were anaemic; 12 patients had iron deficiency, and 10 had iron deficiency anaemia (IDA). The median (range) sTfR in the IDA patients was 16.6 (11.2-24.8) mg/l. compared with 6.6 mg/l (11.2-24.8) in the 16 patients with anaemia due to other causes (P = 0.01). The sensitivity of sTfR for diagnosing iron deficiency in CLD was 91.6% (100% if only anaemic patients are included) and the specificity was 84.6%. Patients with haemolysis and recent blood loss may have falsely elevated sTfR levels. The results suggest that the sTfR is as useful as serum ferritin in identifying a potentially treatable cause of anaemia in CLD.     

Hepcidin is the major predictor of erythrocyte iron incorporation in anemic African children

Iron supplementation strategies in the developing world remain controversial because of fears of exacerbating prevalent infectious diseases. Understanding the conditions in which iron will be absorbed and incorporated into erythrocytes is therefore important. We studied Gambian children with either postmalarial or nonmalarial anemia, who were given oral iron supplements daily for 30 days. Supplements administered on days 1 and 15 contained the stable iron isotopes (57)Fe and (58)Fe, respectively, and erythrocyte incorporation was measured in blood samples drawn 14 days later. We investigated how the iron-regulatory hormone hepcidin and other inflammatory/iron-related indices, all measured on the day of isotope administration, correlated with erythrocyte iron incorporation. In univariate analyses, hepcidin, ferritin, C-reactive protein, and soluble transferrin receptor (sTfR) strongly predicted incorporation of (57)Fe given on day 1, while hepcidin, ferritin, and sTfR/log ferritin correlated with (58)Fe incorporation. In a final multivariate model, the most consistent predictor of erythrocyte isotope incorporation was hepcidin. We conclude that under conditions of competing signals (anemia, iron deficiency, and infection), hepcidin powerfully controls use of dietary iron. We suggest that low-cost point-of-care hepcidin assays would aid iron supplementation programs in the developing world.     

Serum hepcidin‐25 may replace the ferritin index in the Thomas plot in assessing iron status in anemic patients

Introduction: Biochemical markers of iron deficiency do not distinguish iron‐deficient anemia (IDA) from the anemia of chronic disease (ACD) and the combined state of ACD/IDA. Serum hepcidin‐25 might be a marker resolving this problem. We investigated the extent to which serum hepcidin‐25 enables the differentiation of the states above in comparison with the ferritin index plot, the so‐called Thomas plot [soluble transferrin receptor (sTfR)/log ferritin and the reticulocyte hemoglobin content (CHr)]. Methods: Serum hepcidin‐25 was determined in 155 anemic patients who were classified as having latent iron deficiency (latent ID), IDA, ACD, or ACD/IDA using the ferritin index plot (Thomas plot). Hepcidin‐25 was determined using an isotope‐dilution micro‐HPLC‐tandem mass spectrometry method. The ability to discriminate among these states based on serum hepcidin‐25 alone or in combination with the CHr was evaluated in a receiver operating characteristic curve analysis and a comparison with the recently established ferritin index plot. Results: Serum hepcidin‐25 correlated with ferritin and the ferritin index. Use of a hepcidin‐25 cutoff level of ≤4 nmol/l allowed the differentiation of IDA from ACD and ACD/IDA. Furthermore, the discrimination of ACD/IDA from ACD required combination with CHr in a new plot (hepcidin‐25 and the CHr). The hepcidin‐25 plot and the ferritin index plot showed a good correspondence in the differentiation of iron states in patients with anemia. Conclusion: Patients with IDA can be differentiated from ACD and ACD/IDA but not ACD from ACD/IDA based on hepcidin‐25 alone. The combination of hepcidin‐25 with CHr in the hepcidin‐25 plot was useful for the differentiation of the states above.