Marker Of Iron Deficiency Anemia Research Articles

Reticulocyte Hemoglobin Equivalent (Ret-He) as a Potential Diagnostic Marker of Iron Deficiency Anemia among Bangladeshi Adults.

Miah MMZ, Pramanik MEA, Rafi MA, et al. Reticulocyte Hemoglobin Equivalent (Ret-He) as a Potential Diagnostic Marker of Iron Deficiency Anemia among Bangladeshi Adults. Euroasian J Hepato-Gastroenterol 2023;13(2):128-132.

Cellular Zinc Deficiency Impairs Heme Biosynthesis in Developing Erythroid Progenitors.

Anemia is the most prevalent nutrition-related disorder worldwide. Zinc is an essential trace element for various biological processes in the body, and zinc deficiency has been associated with anemia in humans. However, the molecular mechanisms by which zinc availability alters red blood cell development remain uncertain. The present study identifies the essentiality of zinc during erythroid development, particularly for normal heme biosynthesis. G1E-ER4 mouse cells were used as an in vitro model of terminal erythroid differentiation, which featured elevated cellular zinc content by development. Restriction of zinc import compromised the rate of heme and α-globin production and, thus, the hemoglobinization of the erythroid progenitors. Heme is synthesized by the incorporation of iron into protoporphyrin. The lower heme production under zinc restriction was not due to changes in iron but was attributable to less porphyrin synthesis. The requirement of adequate zinc for erythroid heme metabolism was confirmed in another erythropoietic cell model, MEL-DS19. Additionally, we found that a conventional marker of iron deficiency anemia, the ZnPP-to-heme ratio, responded to zinc restriction differently from iron deficiency. Collectively, our findings define zinc as an essential nutrient integral to erythroid heme biosynthesis and, thus, a potential therapeutic target for treating anemia and other erythrocyte-related disorders.

Soluble transferrin receptor concentration compared with reticulocyte hemoglobin content as a reliable marker of iron deficiency anemia in hemodialysis patients

Abstract Introduction Adequate iron stores are necessary for successful erythropoiesis-stimulating agents (ESAs) therapy in hemodialysis (HD) patients. However, iron status estimation in HD patients remains challenging, as most parameters are affected by inflammation. We aimed to compare the performance of soluble transferrin receptor concentration (sTfR) and reticulocyte hemoglobin content (CHr) as potential markers for iron status assessment. Methods This was a cross-sectional study that included 60 anemic patients with kidney failure on regular HD for a minimum of 3 months. Patients were in the maintenance phase of the ESAs with stable doses for at least 4 weeks and at least 3 weeks free of iron therapy. Patients were classified into two groups; group I: 18 patients with noniron deficiency anemia (NIDA); transferrin saturation (TSAT) greater than 20% and ferritin greater than 200 ng/ml and group II: 42 patients with iron deficiency anemia (IDA); transferrin saturation less than 20% and/or ferritin less than 200 ng/ml. CHr and sTfR were evaluated as reliable markers for diagnosing iron deficiency. Results CHr was significantly lower while sTfR was significantly higher in patients with IDA. Based on the receiver operating characteristic (ROC) curve, the area under the curve (AUC) of sTfR was significantly larger than the area under the curve of CHr; however, this had a borderline significance. Conclusion sTfR has a significantly higher diagnostic power for diagnosis of IDA than CHr.

MO789SERUM SOLUBLE TRANSFERRIN RECEPTOR IS A PROMISING MARKER OF IRON DEFICIENCY ANEMIA IN PREVALENT HEMODIALYSIS PATIENTS

Abstract Background and Aims End stage renal disease (ESRD) is chronic inflammatory condition which affects iron parameters. Serum soluble transferrin receptor (sTfR) is a reliable indicator for assessing iron status in inflammatory conditions. This study evaluates the usefulness of serum sTfR in iron deficiency anemia detection in prevalent hemodialysis patients. Method This case-control study included 40 ESRD patients on conventional hemodialysis with CRP>10, 40 ESRD patients with CRP<10 and 8 apparently healthy controls. Serum sTfR was measured for all patients and controls. Results STFRs predicts iron deficiency anemia in prevalent hemodialysis patients at cut off value 12.5 mg/l with area under curve 0.949, sensitivity 88.75, specificity 100, PPV 100% and NPV 47.1%. The prevalence of STFRs in patients with CRP<10 was 85%, while in patients with CRP>10 was 92.5% (P-value 0.288). 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 haemoglobin and STFR with P-value 0.0001 and 0.0001 respectively. Post Hoc analysis showed significant difference between the patients with CRP<10 and control also in patients with CRP>10 and control as regard haemoglobin and STFR (p value <0.0001). 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 haemoglobin (p value 0.642) and classic iron markers (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 in patients with CRP <10 (r -0.372, P-value 0.018) and (r-0.416, p value 0.008) respectively. Conclusion Serum soluble transferrin receptor is a highly sensitive and specific marker of iron deficiency anemia in hemodialysis patients especially with high CRP level.

Hepcidin Is a Reliable Marker of Iron Deficiency Anemia in Newly Diagnosed Patients with Inflammatory Bowel Disease.

Results There was a high statistically significant difference between IBD patients and controls in levels of hepcidin (P < 0.01). Namely, serum hepcidin levels were significantly higher in the control group. There was no statistically significant correlation of serum hepcidin with CRP, Mayo score, or CDAI, respectively (P > 0.05). However, we have found a statistically significant negative correlation of sTfR and TIBC with hepcidin (P < 0.01). Conclusion Results of our study suggest that hepcidin is a reliable marker of IDA in patients with IBD, and it could be used in routine clinical practice when determining adequate therapy in these patients.

Evaluation of Urinary Hepcidin as a Marker for the Early Diagnosis of Iron Deficiency Anemia in Children

Background: Iron deficiency is an essential element, because nearly all living organism urine hepcidin levels could potentially be used in the determination of iron requirements and be an accurate indicator of physiological IDA. Aim: The present study aimed to evaluate the role of urinary hepcidin as an early diagnostic marker of iron deficiency anemia in children. Methods: This study included 45 children. Their age ranged from 6 to 16 years with hemoglobin levels ≤ 11.5 gm/dL and ferritin levels ≤ 20 ng/mL. The diagnostic performance of urinary hepcidin was estimated by analyzing the receiver operating characteristic curve. Diagnostic cut-off point with a high predictive value for iron deficiency was selected. Results: This study showed no statistically significant difference between the two studied groups regarding to demographic data. There were decrease in serum iron, ferritin, hemoglobin and Red blood cells (RBCs) indices in patient than the control group. There was non-significant decrease in urinary hepcidin in the study group compared to control group. The sensitivity and specificity of urinary hepcidin in diagnoses of iron deficiency anemia was 57.8 and 62.2 respectively with positive predictive value (63.3) in our study. There was positive correlation between urinary hepcidin and mean corpuscular volume (MCV), (r = 0.221), (p = 0.036), with the cut of value Conclusion: We concluded that the decrease of urinary level of hepcidin was non-significant in iron deficiency anemia compare to control group and needed further researches.

Association between serum ferritin levels and clinical outcomes in maintenance hemodialysis patients: a retrospective single-center cohort study

BackgroundFerritin is a well-known marker of iron deficiency anemia, but the target in maintenance hemodialysis (MHD) patients remains controversial. This study examined the association between baseline ferritin levels and clinical outcomes.MethodsWe retrospectively collected the data of outpatients on MHD for 5 years at St. Luke’s International Hospital from July 2009. Patients with baseline ferritin levels of > 100 ng/mL in June 2009 were defined as the high-ferritin (HF) group and the remaining patients as the low-ferritin (LF) group. The primary endpoint was all-cause mortality. The secondary endpoints included cardiovascular events and infection-related hospitalizations. Log-rank test and Cox proportional hazard analysis were performed.ResultsOf 116 patients (age, 65.4 ± 13.4 years, 70% males), 29 (25%) and 87 (75%) belonged to the HF and LF groups, respectively. During the follow-up period of 1825 (interquartile range 819–1825) days, 38 patients (23 in the HF and 15 in the LF groups) died. According to the Kaplan–Meier survival curves, the HF group had significantly poor survival compared with the LF group (p = 0.0089). After adjusting for age, sex, vintage of hemodialysis, C-reactive protein levels, and history of cardiovascular events, the hazard ratio (HR) for the HF group was 2.49 (95% confidence interval (CI), 1.21–5.12). The multivariate analysis of cardiovascular events revealed a similar result with statistical significance (HR 2.69; 95% CI 1.12–6.46). Infection-related hospitalizations did not exhibit any statistically significant difference.ConclusionsIn MHD patients, ferritin levels > 100 ng/mL is associated with increased rates of all-cause mortality and cardiovascular events.

Serum Soluble Transferrin Receptor-Ferritin Indices in Diagnosing and Differentiating Iron Deficiency Anemia from Anemia of Chronic Disease among Patients with Chronic Kidney Disease

Background: Anemia is common in patients with chronic kidney disease (CKD) and this is generally anemia of chronic disease (ACD), but iron deficiency anemia (IDA) is also common. Soluble transferrin receptor (sTfR) is a useful marker for IDA. Present study was undertaken to assess the utility of sTfR as a marker of IDA and to differentiate ACD from IDA in selected group of Bangladeshi patients with CKD.&#x0D; Methods: This cross-sectional study was conducted in the Department of Nephrology, BSMMU, Dhaka, Bangladesh from January 2013 to December 2014. Patients with anemia admitted in Nephrology Department, whether on hemodialysis or not and Medicine Department of BSMMU were taken for study. The study population was further divided into two groups; Group A, patients (30) who were having IDA and Group B, patients (40) with ACD and a control group was also selected. Data were collected by face to face interview and laboratory investigations with a self-administered questionnaire.&#x0D; Results: The mean age of the patients in Group A and Group B were 38.40±13.23 and 34.85±10.52 years respectively and male-female ratio were 0.5:1 and 1:0.5. Mean sTfR level was higher (4.81± 1.64 μg/ml) in patients with IDA than (2.89±1.40 μg/ml) in patients with ACD (p &lt;0.0001). Mean ferritin level was 599.59± 449.15μg/L in ACD patients whereas 101.23±119.42 in IDA patients (p&lt;0.0001). Total iron binding capacity (TIBC) was more in ACD patients with sTfRe”3μg/ml as compared to ACD patients with sTfR&lt;3μg/ml. Transferrin saturation (TSAT) level was significantly decreased in ACD patients with sTfRe”3μg/ml as compared to ACD patients with sTfR&lt;3μg/ml. sTfR and ferritin indices between group A (IDA) and group B (ACD) shows mean sTfR:logSF level was significantly (P&lt;0.001) high in group A (2.71±1.13) in comparison to group B (1.08±0.54). Mean log sTFR:SF was also significantly higher (P&lt;0.05) in group A (0.001±0.0008) compared to group B (0.013±0.012).&#x0D; Conclusion: sTfR level has a comparable ability to serum ferritin in diagnosing IDA and ACD. However, sTfR and serum ferritin alone cannot definitely exclude coexisting iron deficiency in ACD. Log sTfR/ ferritin index has role in identifying development of iron deficiency in ACD whereas sTfR/ log SF ratio can differentiate pure IDA from ACD with or without iron deficiency. Thus, it is important to estimate both serum sTfR and sTfRferritin indices to be able to differentiate pure IDA, ACD and ACD with co-existing iron deficiency thus providing a non-invasive alternative to bone marrow iron.&#x0D; Birdem Med J 2019; 9(2): 151-156

Iron deficiency anemia among hospitalized children in a rural teaching hospital: a cross sectional study

Background: Iron deficiency anemia is the most common nutritional deficiency disorder in the world. The present study was conducted to know the prevalence and severity of iron deficiency anemia among of 6 months to 60 months old children. A large proportion of iron deficiency is preventable with appropriate and timely intervention.Methods: This cross-sectional study was done on 100 children clinically suggestive of anemia with hemoglobin level less than 11gm/dl admitted in pediatrics ward of tertiary care hospital. 5 ml of blood sample was taken and complete hemogram, peripheral blood film and serum ferritin estimation was done. Case were studied in reference to history, age, clinical examination, hemoglobin level and confirmation of iron deficiency anemia was done by serum ferritin levels.Results: The prevalence of iron deficiency anemia in present study was 56%. It was most prevalent in the age group of 6 to 24 months. Exclusively breastfed children showed higher prevalence of iron deficiency anemia in present study, however no statistical correlation was found. Low Serum ferritin levels have statistically significant result with socioeconomic status, with as many as 69.4% suffering from iron deficiency anemia belonging to low socioeconomic status.Conclusions: Prevalence of iron deficiency anemia remains alarmingly high and major health problem in our country. All anemia are not iron deficiency anemia. Low socioeconomic status is a huge hurdle in child health and greatly influences prevalence of iron deficiency anemia. Serum ferritin is a most sensitive marker of iron deficiency anemia, helps diagnose it early in its course, which can be missed on clinical or routine blood investigations.

Aggregation-Induced Emission Probe for Specific Turn-On Quantification of Soluble Transferrin Receptor: An Important Disease Marker for Iron Deficiency Anemia and Kidney Diseases.

Transferrin receptor (TfR) is overexpressed on the surface of many cancer cells due to its vital roles in iron circulation and cellular respiration. Soluble transferrin receptor (sTfR), a truncated extracellular form of TfR in serum, is an important marker of iron deficiency anemia (IDA) and bone marrow failure in cancer patients. More recently, sTfR level in urine has been related to a specific kidney disease of Henoch-Schönlein purpura nephritis (HSPN). Despite the universal significance of sTfR, there is still a lack of a simple and sensitive method for the quantification of sTfR. Furthermore, it is desirable to have a probe that can detect both TfR and sTfR for further comparison study. In this work, we developed a water-soluble AIE-peptide conjugate with aggregation-induced emission (AIE) characteristics. Taking advantage of the negligible emission from molecularly dissolved tetraphenylethene (TPE), probe TPE-2T7 was used for the light-up detection of sTfR. The probe itself is nonemissive in aqueous solution, but it turns on its fluorescence upon interaction with sTfR to yield a detection limit of 0.27 μg/mL, which is much lower than the sTfR level in IDA patients. Furthermore, a proof-of-concept experiment validates the potential of the probe for diagnosis of HSPN by urine test.

Role of Serum Transferrin Receptor in Diagnosing and Differentiating Iron Deficiency Anemia from Anemia of Chronic Disease in Patients with Chronic Kidney Disease

Background: Anemia is common in patients with chronic kidney disease (CKD) and this is generally anemia of chronic disease, but iron deficiency anemia (IDA) is also common. Soluble transferrin receptor (sTfR) is a useful marker for IDA. Present study was undertaken to assess the utility of sTfR as a marker of IDA in selected group of Bangladeshi patients with CKD.Methods: This cross-sectional study was conducted in the Department of Nephrology, BSMMU, Dhaka, Bangladesh from January 2013 to December 2014. Patients with anemia admitted in nephrology department whether on hemodialysis or not and medicine department of BSMMU were taken for study. The study population was further divided into two groups; Group A, patients who are having IDA and Group B, patients with ACD and a control group was also selected. Data were collected by face to face interview and laboratory investigations with a self-administered questionnaire.Results: The mean age of the patients in two study groups were 38.40±13.23 and 34.85±10.52 years respectively and male-female ratio were 0.5:1 and 1:0.5. Mean sTfR level was higher (4.81± 1.64 ?g/ml) in patients with IDA than (2.89±1.40 ?g/ml) in patients with ACD (p &lt;0.0001). In our study mean ferritin level was 599.59± 449.15?g/L in ACD patients whereas 101.23±119.42 in IDA patients (p&lt;0.0001). Total iron binding capacity (TIBC) was more in ACD patients with sTfRe”3?g/ml as compared to ACD patients with sTfR&lt;3?g/ml. Transferrin saturation (TSAT) level was significantly decreased in ACD patients with sTfR ?3?g/ml as compared to ACD patients with sTfR&lt;3?g/ml.Conclusion: sTfR has a comparable ability to S. ferritin in diagnosing IDA and ACD. However, sTfR and serum ferritin alone cannot definitely exclude co-existing iron deficiency in ACD. As sTfR is not affected by infection and/or inflammation, thus providing a non-invasive alternative to bone marrow study.Birdem Med J 2017; 7(2): 132-137

Red Cell Distribution Width and Mortality inHemodialysisPatients.

Red cell distribution width (RDW) is an index of red blood cell volume variability that has historically been used as a marker of iron deficiency anemia. More recently, studies have shown that elevated RDW is associated with higher mortality risk in the general population. However, there is lack of data demonstrating the association between RDW and mortality risk in hemodialysis (HD) patients. We hypothesized that higher RDW is associated with higher mortality in HD patients. Retrospective observational study using a large HD patient cohort. 109,675 adult maintenance HD patients treated in a large dialysis organization from January 1, 2007, to December 31,2011. Baseline and time-varying RDW, grouped into 5 categories:<14.5%, 14.5% to<15.5%, 15.5% to<16.5%, 16.5% to<17.5%, and≥17.5%. RDW of 15.5% to<16.5% was used as the reference category. All-cause mortality. Mean age of study participants was 63±15 (SD) years and the study cohort was 44% women. In baseline and time-varying analyses, there was a graded association between higher RDW and incrementally higher mortality risk. Receiver operating characteristic, net reclassification analysis, and integrated discrimination improvement analyses demonstrated that RDW is a stronger predictor of mortality as compared with traditional markers of anemia, such as hemoglobin, ferritin, and iron saturation values. Lack of comprehensive data that may be associated with both RDW and HD patient outcomes, such as blood transfusion data, socioeconomic status, and other unknown confounders; therefore, the possibility of residual confounding could not be excluded. Also, lack of information for cause of death; thus, cardiovascular mortality outcomes could not be examined. In HD patients, higher RDW is associated with incrementally higher mortality risk. RDW is also a stronger predictor of mortality than traditional laboratory markers of anemia. Further studies are needed to determine the mechanisms underlying the association between RDW and mortality.

Salivary Ferritin as a Predictive Marker of Iron Deficiency Anemia in Children

The objective of the study was to determine the salivary Ferritin levels in children with iron deficiency anemia and its reliability as a predictive marker of the disease and whether these levels could give a new hypothetical insight on the oral epithelial changes seen in patients with iron deficiency anemia. The study comprised of 60 children of which the study group comprised of 30 individuals; aged 8-14 years with iron deficiency anemia. Venous blood was collected and hematological examination was performed to determine the hemoglobin and serum ferritin levels to confirm the diagnosis. Saliva was then collected from 30 children with iron deficiency anemia and an equal number of controls. The ferritin levels in saliva were then analyzed using solid phase ELISA. The mean value of salivary ferritin in iron deficient cases was 153.24 +/- 46.58 microg/dl and the mean ferritin levels in control subject were 93.87 +/- 30.15 microg/dl. Thus the salivary ferritin was found to be significantly higher in iron deficient subjects compared to the controls. The result of our research affirms the fact that the expression of ferritin in saliva of iron deficiency anemia may be due to the enzymatic functions in the saliva and the endocytosis of ferritin which can possibly elevate the salivary ferritin. The diminished level of cytochrome oxidase, together with its relatively high Ferritin content, depicts the association of oral epithelial changes and ferritin occurring in iron deficiency anemia.

血液透析患者における鉄欠乏の指標としての網状赤血球ヘモグロビン量,低色素赤血球比率,血清トランスフェリンレセプター/血清鉄比の有用性

Reticulocyte hemoglobin content(CHr), percentage of hypochromic red blood cells(%HRC, level of serum transferrin receptor(sTfR), and sTfR/serum iron ratio(sTfR/Fe) were measured in 132 hemodialysis patients. On univariate analysis, CHr was positively correlated with serum amyloid A(SAA) and negatively correlated with Kt/V. %HRC showed a positive correlation with the recombinant human erythropoietin(rHuEPO) dosage. The dependency of each iron-status index on 5 variables, SAA, sFt, TS, KtN, and dose of rHuEPO administered, was determined by stepwise multiple regression analysis. CHr was influenced only by TS, while %HRC, sTfR and sTfR/Fe were influenced by both logrHuEPO dosage and TS. Patients whose hemoglobin concentration increased by more than 1 g/dl following iron supplementation were defined as Iron-Responders, and the remaining patients were defined as Iron-Nonresponders. Fifteen out of 20 patients responded to 10 consecutive intravenous administrations of 80 mg of saccharated ferric oxide at each dialysis session, while five did not. The baseline CHr was significantly lower in Iron-Responders than Iron-Nonresponders. The baseline %HRC, sTfR, and sTfR/Fe were significantly higher in Iron-Responders than Iron-Nonresponders. The baseline CHr, %HRC, and sTfR/Fe were correlated with the degree of change in Hb concentration at 4 weeks of iron supplementation. The absolute change in CHr at 2 weeks of iron supplementation was positively correlated with the absolute change in Hb concentration over the first 4 weeks. (1) In assessing the iron metabolic status of dialysis patients, CHr, %HRC, and sTfR/Fe were unique indices compared with the ordinary indices, particularly in diagnosing the functional iron deficiency state. (2) CHr was a valuable marker of iron deficiency anemia and could predict the degree of increase in Hb level following iron supplementation. (3) The %HRC and sTfR/Fe seemed to reflect both erythropoiesis induced by rHuEPO and the iron supply to erythropoietic cells.

Is soluble transferrin receptor a good marker of iron deficiency anemia in chronic kidney disease patients?

Anemia in patients with chronic renal failure is multifactorial with an absolute or functional iron deficiency present in 60–80% of patients. In this study, 102 patients of stage 5 chronic kidney disease (CKD) were enrolled. Thirty six age- and sex-matched anemic patients without any known renal disease were taken as controls. Their sTfR levels were measured with anemia profile.(Fe, TIBC, Ferritin, TSAT). The patients were followed up twice, at four weeks and six months. There was a significant statistical difference in the mean sTfR levels in patients when compared to controls (P < 0.01).The mean level of sTfR in CKD patients was 3.23 ± 2.07 mg/l while in controls this was 5.16 ± 3.64 mg/l. sTfR had no statistically significant correlation with the levels of hemoglobin, iron, ferritin, TIBC and TSAT. We conclude that owing to complexity of iron metabolism in CKD, sTfR can not be used as a reliable marker of iron deficiency anemia.

Soluble transferrin receptor level: a new marker of iron deficiency anemia, a common manifestation of gastric autoimmunity in type 1 diabetes.

A total of 15-20% of type 1 diabetic patients have parietal cell antibodies (PCAs). PCA+ subjects are at increased risk for iron deficiency anemia and atrophic gastritis. Recently, soluble transferrin receptor (sTfR) levels have proven to be a sensitive indicator for iron deficiency They are, in contrast with ferritin levels, independent of inflammation, liver and hormonal status, and sex. We are the first to evaluate sTfR levels in type 1 diabetes and tested the hypothesis of higher sTfR levels in patients with PCAs and/or autoimmune gastritis. We examined 148 type 1 diabetic patients (85 men and 63 women; 50 were PCA+) and 59 sex- and age-matched control subjects (30 men and 29 women). The main outcome measures were sTfR levels, iron deficiency anemia, and atrophic gastritis. Logistical regression analysis tested risk factors for iron deficiency Iron deficiency was present in 38 subjects. Iron (P<0.0001) and ferritin (P<0.0001) levels but not sTfR levels were lower in women. sTfR levels were similar in diabetic and control subjects but were higher in PCA+ subjects (P = 0.015). In diabetic subjects, iron deficiency anemia was more prevalent in PCA+ than in PCA- patients (odds ratio 3.07, P = 0.013) and was associated with sex (P = 0.0001), age (P = 0.046), and sTfR (P = 0.0008) levels. Atrophic gastritis was present in 15 of 28 PCA+ and in 1 of 11 PCA diabetic subjects (P = 0.014). sTfR levels tended to be higher in patients with atrophic gastritis (P = 0.062). In type 1 diabetes, sTfR levels can be used to diagnose iron deficiency anemia, which is more prevalent in PCA+ subjects. sTfR levels are higher in PCA+ individuals who are at risk for developing atrophic gastritis.