Serum transferrin receptors: Distribution and diagnostic performance in pre-school children

Soluble transferrin receptors have gained interest in the field of diagnosing anemias. Reference ranges differ according to the method used for the quantification of sTfR. We aim to explore the distributional properties and diagnostic performance of sTfR in pre-school healthy children as well as in children with β-thalassemia carriers, iron deficiency with normal hematological phenotype (ID) and iron deficiency anemia (IDA). Circulating sTfR as well as biochemical and hematological indices were determined in 521 pre-school children and four groups (normal children, β-thalassemia traits, ID and IDA) were formed. Diagnostic performance and distribution of sTfR according to age and in relation to several parameters were evaluated in every group. Three hundred eighty one children (261 normal, 60 β-thalassemia traits, 44 ID and 16 IDA) aged 1–6 years were included. We found that distribution of sTfR differed significantly among the four groups (Kruskal Wallis p < 0.001) with children in the normal group exhibiting lower concentrations compared to all other. A negative correlation between sTfR and age occurred in the normal (β = − 0.12, p < 0.001) and the ID groups (β = − 0.13, p = 0.035). In the β-thal and IDA groups sTfR is correlated to HbA₂ (β = 0.34, p = 0.001) and ferritin (Spearman's rho = − 0.6, p = 0.014) respectively. An area under the curve equal to 0.63 was achieved by sTfR in distinguishing between normal and ID children. Sensitivity and specificity were 70.5% and 50% respectively at a cut-off of 2.5 mg/l. Levels of sTfR are negatively correlated to age in pre-school children while dyserythropoietic procedures like β-thal, ID, and IDA significantly affect them. These findings indicated that the accuracy of sTfR in diagnosing ID from normal children is limited. Standardization will allow the use of formulas that combine sTfR and ferritin which are of greater diagnostic value than sTfR alone.     

Causes of iron deficiency anemia in an adult inpatient population

Summary The causes of iron deficiency anemia in a population of adults admitted to two Jerusalem hospitals within a period of 7 years were examined. About one half of the 262 patients with iron deficiency anemia were over 70 years old. The ratio of males to females exclusive of young females with menorrhagia was 1:1.8. Despite the combined use of various diagnostic procedures, no definite cause of iron deficiency anemia could be established in 34% of patients. Benign gastrointestinal lesions were found in about one half of the cases in both hospitals. The prevalence of GI neoplasms in hospital B with a more intensive use of endoscopic procedures was significantly higher than in hospital A (18% vs 5%, p<0.001). The relative usefulness of barium contrast vs endoscopic studies is illustrated by the fact that 22 diagnoses established by endoscopy were missed by barium studies, whereas only 2 of those established by barium studies were not visualized by endoscopy. A particularly high risk group were anemic males aged 50 to 69 years in whom the prevalence of GI neoplasms was 30%. These data indicate that reliance on traditional contrast radioscopy may result in misdiagnosis of a high proportion of gastrointestinal neoplasms.     

A guide to diagnosis of iron deficiency and iron deficiency anemia in digestive diseases

Iron deficiency （ID）, with or without anemia, is often caused by digestive diseases and should always be investigated, except in very specific situations, as its causes could be serious diseases, such as cancer. Diagnosis of ID is not always easy. Low serum levels of ferritin or transferrin saturation, imply a situation of absolute or functional ID. It is sometimes difficult to differentiate ID anemia from anemia of chronic diseases, which can coexist. In this case, other parameters, such as soluble transferrin receptor activity can be very useful. After an initial evaluation by clinical history, urine analysis, and serological tests for celiac disease, gastroscopy and colonoscopy are the key diagnostic tools for investigating the origin of ID, and will detect the most important and prevalent diseases. If both tests are normal and anemia is not severe, treatment with oral iron can be indicated, along with stopping any treatment with non-steroidal anti-inflammatory drugs. In the absence of response to oral iron, or if the anemia is severe or clinical suspicion of important disease persists, we must insist on diagnostic evaluation. Repeat endoscopic studies should be considered in many cases and if both still show normal results, investigating the small bowel must be considered. The main techniques in this case are capsule endoscopy, followed by     

Phenotypic expression of hemoglobin A2 in beta-thalassemia trait with iron deficiency

 Iron status was estimated in 463 heterozygous beta-thalassemics to delineate the effect of iron deficiency on the expression of hemoglobin A₂ (HbA₂) in these patients. One hundred and twenty-six (27.2%) patients with the trait were iron deficient. These iron-deficient patients had a significantly (p<0.0002) higher prevalence of anemia (90.5%) compared with iron-replete patients with the trait (71.5%). The mean hemoglobin (Hb) concentration, MCV, and MCH were significantly (p<0.0001) lower in patients with beta-thalassemia traits (BTT) who had iron deficiency than in those without iron deficiency. Mean RBC count and MCHC did not differ in the two groups. Mean HbA₂ was not significantly different in the two groups of patients with the trait and was elevated ( 1 3.5%) in all but one heterozygote investigated. Mean HbA₂/cell was significantly (p<0.05) lower in BTT patients with iron deficiency than in patients without iron deficiency. The presence of iron deficiency did not preclude the detection of BTT in this population. The effect of iron deficiency in BTT was apparent as a significant lowering of the Hb concentration and an increased prevalence of anemia. Iron therapy is warranted for BTT patients with iron-deficiency traits and would help to significantly raise their Hb concentration. The elevation ofHbA₂ was striking and could be used with reliability in making the diagnosis of BTT even in the presence of iron deficiency. Received: January 26, 1998 / Accepted: June 2, 1998     

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.     

Prevalence and spectrum of iron deficiency in heart failure patients in south Rajasthan

ObjectiveTo estimate the prevalence and pattern of iron deficiency (ID) in heart failure (HF) patients with or without anemia.MethodsThis is a single-center observational study, conducted at a tertiary care hospital of south Rajasthan. Patients admitted to hospital with clinical diagnosis of HF based on validated clinical criteria were included in the study. ID was diagnosed based on complete Iron profile, including serum iron, serum ferritin, total iron binding capacity, and transferrin saturation (TSAT). Anemia was defined as hemoglobin (Hb) <13 g/dl for males and <12 g/dl for females, based on World Health Organization definition. Absolute ID was taken as serum ferritin < 100 μg/L and functional ID was defined as normal serum ferritin (100–300 μg/L) with low TSAT (<20%).ResultsA total of 150 patients of HF (68% males and 32% females) were studied. Most of the patients were of high-functional NYHA class (mean NYHA 2.89 ± 0.95). ID was present in 76% patients with 48.7% patients having absolute and 27.3% patients having functional ID. Females were having significantly higher prevalence of ID than males (91.6% vs 68.6%; p = 0.002). Nearly one-fourth of the patients were having ID but without anemia, signifying importance of workup of ID other than Hb.ConclusionOur study highlights the yet underestimated and neglected burden of ID in HF patients in India. This study suggests further large-scale studies to better characterize this easily treatable condition and considering routine testing in future Indian guidelines.     

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.     

Relationship between glycosylated hemoglobin and iron deficiency anemia: A common but overlooked problem

IntroductionBoth diabetes mellitus (DM) and iron deficiency anemia (IDA) are prevalent in every area of the world, and so, the possibility of these two diseases co-existing is also very high. It is our belief that clinical results of any correlation between iron status of the body and glycosylated haemoglobin (HbA1c) would be beneficial to many patients, therefore in this study, the effect of IDA on HbA1c was investigated.Materials – methodsA total of 146 patients with DM and IDA were evaluated prospectively. While the patients were administered 270 mg/day of ferrous sulphate (80 mg elemental iron) orally for three months for the treatment of IDA, no interventions were made for the treatment of DM. Patient levels of hemoglobin (Hb), hematocrit, red blood cells (RBC), mean corpuscular volume (MCV), platelet, white blood cells (WBC), serum iron, serum iron binding capacity (SIBC), ferritin, fasting plasma glucose (FPG), HbA1c, body mass index (BMI), C-reactive protein (CRP) values were measured at baseline and at the third month of treatment with iron, and were compared.ResultsThe median age of our patients was 45 (40–50) and median duration of diabetes was 3 years (1,75–5). While the baseline median Hb was 10.4 (mg/dL) (9.5–11.1), MCV was 74 (fL) (70.8–77), ferritin was 4 (ug/L) (3–6) at three months, Hb was measured at 12.6 (mg/dL) (12.1–13.2), MCV was measured at 82 (fL) (80–86), ferritin was measured at 15 (ug/L) (9–21.2) and was significantly higher compared to baseline values (p < 0.001). The baseline median HBA1c of patients was 7.09 ± 0.51 (%) and three month HBA1c was 6.69 ± 0.53 (%), which was significantly lower than when comparing baseline values with values at third month (p < 0.001). Baseline and three month values for FPG were 118 (mg/dL) (108–132) and 116 (mg/dL) (106–125) respectively, and there was no significant difference (p:0.07). A 2.2 mg/dL (1.5–3.5) increase in median Hb level accompanied a 0.4 % (0.2–0.6) decrease in median HbA1c levels (Spearman rho = ?0.362; p < 0.001).ConclusionOur study has shown conclusivly that IDA is related to increased HbA1c concentrations and HbA1c decreases significantly following treatment with iron. IDA should be considered before making any decisions regarding diagnosis or treatment according to HbA1c.     

Evaluation of serum ferritin in screening for iron deficiency in tuberculosis

Serum ferritin (SF) values 10 µg/l are diagnostic of absent Bone Marrow Iron (BMI) stores and therefore of iron deficiency (ID). However, SF, which may be elevated as a part of acute phase reaction, is an unreliable indicator of BMI stores in the setting of chronic disorders, making it difficult to diagnose ID in these patients. Thus, in chronic disorders (CD) such as tuberculosis, bone marrow examination is the only reliable way to establish ID. This study was done in order to identify levels of SF that would be indicative of absent BMI stores and also to study a combination of hematological and biochemical parameters that would be helpful in raising the predictive power of SF in patients of tuberculosis. Fifty-five tuberculosis patients were studied and classified into Iron Deplete (ID) and Iron Replete (IR) based on BMI. Raising the cut-off values of SF from 10 µg/l to 30 µg/l diagnosed 88% of ID cases correctly, as compared with 61% when cut-off levels of 10 µg/l were used. At cut-off values higher than 30 µg/l, the sensitivity was markedly reduced. Therefore, raising cut-off levels of SF to 30 µg/l was most effective in predicting absent BMI, especially in a population where ID is highly prevalent. Combination of SF 30 µg/l with mean corpuscular volume (MCV), erythrocyte sedimentation rate (ESR) and total iron binding capacity (TIBC) did not improve the predictive power of SF further. Also, 89.5% cases could be correctly classified by logistic regression equations using SF with ESR and C- reactive protein (CRP).Abbreviations SF Serum ferritin - BMI Bone marrow iron - ID Iron deplete - IR Iron replete - CD Chronic disorders - MCV Mean corpuscular volume - TIBC Total iron binding capacity - ESR Erythrocyte sedimentation rate - ACD Anemia of chronic disorders - IDA Iron deficiency anemia - Hb Hemoglobin concentration - TLC Total leukocyte count - RBC Red blood cell - RDW Red cell distribution width - % TS Percent transferrin saturation - SI Serum iron     

铁代谢指标测定对慢性病贫血并发缺铁的诊断意义

目的 :了解血清铁蛋白 (SF)、转铁蛋白饱和度 (TS)、血清转铁蛋白受体 (sTFR)及sTFR/log(SF)等外周血铁代谢指标对缺铁性贫血 (IDA)、慢性病贫血 (ACD)和慢性病贫血并发缺铁 (ACD/ID)的鉴别诊断意义。方法 :病例为IDA患者 18例 ,ACD患者 2 0例 ,其中 10例为ACD/ID患者。SF测定采用微粒酶免疫法 ,TS测定采用化学发光法 ,sTFR测定采用双夹心抗体酶联免疫吸附法。结果 :IDA患者的SF值、TS值显著低于ACD患者 ,其sTFR、sTFR/log(SF)值显著高于ACD患者。ACD患者中 ,ACD/ID患者与无缺铁的ACD(ACD/IR)患者间SF值无显著差别 ;但ACD/ID患者的TS值明显低于ACD/IR患者 ,而sTFR和sTFR/log(SF)值则显著高于ACD/IR患者。TS<4 0 %对ACD/ID检出的敏感性为 10 0 % ,特异性为 6 7% ;sTFR >30nmol/L对ACD/ID检出的敏感性为 90 % ,特异性为 82 % ;sTFR/log(SF) >2 0对ACD/ID检出的敏感性和特异性均为 90 %。结论 :新的铁代谢指标sTFR ,尤其是sTFR/log(SF)是传统铁代谢指标的必要补充 ,联合应用上述铁代谢指标可对ACD、IDA和ACD/ID患者进行准确的鉴别诊断。     

铁缺乏对妊娠期甲状腺功能影响的研究进展

铁缺乏症(irondeficiency,ID)会增加妊娠期甲状腺功能减退症(甲减)的发生风险.目前认为其发生与甲状腺轴及核受体介导的信号转导通路、甲状腺过氧化物酶及脱碘酶活性、甲状腺自身免疫损伤以及补碘效果等有关.近来研究显示,补铁治疗能够改善甲状腺功能并缓解甲减患者的症状,提示铁剂可能在妊娠期甲减的治疗中扮演重要角色...     

UK guidelines on the management of iron deficiency in pregnancy

Iron deficiency is the most common deficiency state in the world, affecting more than 2 billion people globally. Although it is particularly prevalent in less-developed countries, it remains a significant problem in the developed world, even where other forms of malnutrition have already been almost eliminated. Effective management is needed to prevent adverse maternal and pregnancy outcomes, including the need for red cell transfusion. The objective of this guideline is to provide healthcare professionals with clear and simple recommendations for the diagnosis, treatment and prevention of iron deficiency in pregnancy and the postpartum period. This is the first such guideline in the UK and may be applicable to other developed countries. Public health measures, such as helminth control and iron fortification of foods, which can be important to developing countries, are not considered here. The guidance may not be appropriate to all patients and individual patient circumstances may dictate an alternative approach.     

Treatment of iron deficiency anemia associated with gastrointestinal tract diseases

The gastrointestinal (GI) tract is a common site of bleeding that may lead to iron deficiency anemia (IDA). Treatment of IDA depends on severity and acuity of patients’ signs and symptoms. While red blood cell transfusions may be required in hemodynamically unstable patients, transfusions should be avoided in chronically anemic patients due to their potential side effects and cost. Iron studies need to be performed after episodes of GI bleeding and stores need to be replenished before anemia develops. Oral ...     

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.     

The missed opportunities to diagnose and treat iron deficiency in patients hospitalized with heart failure

Introduction

Iron Deficiency (ID) is common in heart failure (HF), and is an independent contributor to mortality and morbidity.We examined whether patients with previously known HF who were recently hospitalized, had previous treatment for ID, were investigated for it at the time of hospitalization, and, if ID was found, were prescribed iron on discharge.

Methods

We examined the records of 76 consecutive patients admitted to our hospital medical wards with a primary diagnosis of HF.

Results

Anemia (Hb < 12 g/dl) was found in 42/76 patients (55.3%). In 55/76 patients (72.4%) there was no iron workup, in 6 (7.9%) an incomplete iron workup with serum iron, transferrin or ferritin lacking and in 15/76 (19.7%) a complete iron workup.If ID was defined as either a serum ferritin of < 100 μg/l or a serum ferritin of 100–299 μg/l and a %Transferrin Saturation of < 20% it was found in 12/15 (80%) of those with a complete workup; in 9 of 10 (90%) of the anemic patients and in 3 of 5 (60%) of those non-anemic patients.At discharge 11/15 (73.3%) of those with a complete iron workup were given iron, 10 orally and 1 IV. In those 6 with an incomplete workup 2 were started on oral iron (33.3%) and in those without any workup, 1 of 55 (1.8%) was given oral iron.

In conclusions

ID is common in hospitalized HF patients but is usually not sought after by physicians at the time of admission. However if detected the physicians usually treated it.     

Frequency of iron deficiency anemia in type 2 diabetes - Insights from tertiary diabetes care centres across India

AimTo study the frequency of iron deficiency anemia (IDA) in individuals with type 2 diabetes mellitus (T2DM) seen at tertiary diabetes care centres across India.MethodsThis is a retrospective study (January 1, 2017–December 31, 2019), which included 1137 individuals with T2DM, aged ≥18 years, for whom data on glycemic, lipid and haematological parameters were available. Anthropometric measurements were done using standardized techniques. Biochemical investigations included fasting plasma glucose[FPG], post prandial plasma glucose, HbA1c, lipids and serum ferritin and iron wherever feasible.ResultsOf the 1137 individuals included for the study, 117 (10.3%) were categorized as no ‘iron deficiency’ (ID) group [normal hemoglobin: male ≥13 g/dl, female ≥12 g/dl and normal serum ferritin ≥70 μg/L], 123 (10.8%) as ID group [normal hemoglobin and low serum ferritin <70 μg/L)], 447 (39.3%) as IDA group [low haemoglobin: male <13 g/dl, female <12 g/dl and low serum ferritin] and 450 (39.6%) as ‘anemia of chronic disease’ (ACD) group [low hemoglobin and normal serum ferritin]. The percentage of women having ID (57.7%) and IDA (65.3%) was significantly higher than their male counterparts. ID was most prevalent (61.7%) in the individuals with duration of diabetes <5 years whereas ACD was most prevalent (50.5%) in individuals with long standing diabetes (>10 years). Independent risk factors for IDA were female gender (OR 3.3,95% CI:1.75–6.23, p < 0.001), duration of diabetes (OR 1.05, 95% CI 1.01–1.11, p = 0.028) and FPG (OR 1.01, 95% CI 0.99–1.00, p = 0.018).ConclusionsThere is a need of identifying and monitoring iron status and anemia in patients with T2DM.     

A new iron free treatment with oral fish cartilage polysaccharide for iron deficiency chronic anemia in inflammatory bowel diseases： A pilot study

AIM:To investigate the effect of a new oral preparation,highly concentrated in fish cartilage,in a group of inflammatory bowel diseases(IBD)patients with chronic iron deficient anemia.METHODS:In an open label pilot study,we supple-mented a group of 25 patients(11 with Crohn's disease and 14 with ulcerative colitis)in stable clinical conditions and chronic anemia with a food supplement which does not contain iron but contains a standardized fraction of fish cartilage glycosaminoglycans and a mixture of antioxidants(Captafer Medestea,Turin,Italy).Patients received 500 mg,twice a day during meals,for at least 4 mo.Patients were suggested to maintain their alimentary habit.At time 0 and after 2 and 4 mo,emocrome,sideremia and ferritin were examined.Paired data were analyzed with Student's t test.RESULTS:Three patients relapsed during the study(2 in the 3rd mo,1 in the 4th mo),two patients were lost to follow up and two patients dropped out(1 for orticaria,1 for gastric burning).Of the remaining 18 patients,levels of serum iron started to rapidly increase within the 2nd mo of treatment,P < 0.05),whereas serum ferritin and hemoglobin needed a longer period to significantly improve their serum levels(mo 4)P < 0.05.The product was safe,easy to administer and well tolerated by patients.CONCLUSION:These data suggest a potential new treatment for IBD patients with iron deficiency chronic anemia and warrant further larger controlled studies.     

Independence of in vitro iron absorption from mucosal transferrin content in rat jejunal and ileal segments

Summary Isolated non blood-perfused intestinal segments from normal and irondeficient rats were used in vitro. A modification of the luminal perfusion method according to Fisher and Parsons allowed the comparison of iron and transferrin quantities in the serosal fluid at 15 min intervals. Iron transfer in jejunal and ileal segments was directly proportional to the luminal iron concentration within a dose range of 1 to 100 mol/l, did not show saturation characteristics and was linear over time. Jejunal segments from iron-deficient rats transfered about twice as much iron as the jejunal controls. In ileal segments there was no difference in iron transfer between iron-deficient and control rats; in both cases transfer amounted to approx. 10% of jejunal controls. An exponential correlation was found, when the decreasing transferrin content of the tissue was plotted against the cumulative water transport. Transferrin and albumin release from jejunal and ileal segments into the absorbate cumulated asymptotically, which is typical for wash-out phenomena. As iron transfer cumulated linearly while transferrin release cumulated in an asymptotic manner, the capacity of transferrin to bind iron ions is exceeded roughly 100 times by molar equivalents of iron in the last absorbate fractions. Independence of iron transfer from mucosal transferrin quantities is concluded. As the molar transferrin/albumin ratios do not show significant differences between plasma and the sequence of absorbate samples, a wash-out from the gut's interstitial space is assumed, which makes plasma the most likely origin of transferrin in the mucosa.Supported by a grant of the Deutsche Forschungsgemeinschaft Fo 58/8-2. Part of the results has been presented during the VIth Meeting of the European Intestinal Transport Group [16]