Prognostic Performance of Hematological and Serum Iron and Metabolite Indices for Detection of Early Iron Deficiency Induced Metabolic Brain Dysfunction in Infant Rhesus Monkeys.

BACKGROUND: The current pediatric practice of monitoring for infantile iron deficiency (ID) via hemoglobin (Hgb) screening at one y of age does not identify preanemic ID nor protect against later neurocognitive deficits. OBJECTIVES: To identify biomarkers of iron-related metabolic alterations in the serum and brain and determine the sensitivity of conventional iron and heme indices for predicting risk of brain metabolic dysfunction using a nonhuman primate model of infantile ID. METHODS: Simultaneous serum iron and RBC indices, and serum and cerebrospinal fluid (CSF) metabolomic profiles were determined in 20 rhesus infants, comparing iron sufficient (IS; N = 10) and ID (N = 10) infants at 2 and 4 mo of age. RESULTS: Reticulocyte hemoglobin (RET-He) was lower at 2 wk in the ID group. Significant IS compared with ID differences in serum iron indices were present at 2 mo, but Hgb and RBC indices differed only at 4 mo (P < 0.05). Serum and CSF metabolomic profiles of the ID and IS groups differed at 2 and 4 mo (P < 0.05). Key metabolites, including homostachydrine and stachydrine (4-5-fold lower at 4 mo in ID group, P < 0.05), were altered in both serum and CSF. Iron indices and RET-He at 2 mo, but not Hgb or other RBC indices, were correlated with altered CSF metabolic profile at 4 mo and had comparable predictive accuracy (area under the receiver operating characteristic curve scores, 0.75-0.80). CONCLUSIONS: Preanemic ID at 2 mo was associated with metabolic alterations in serum and CSF in infant monkeys. Among the RBC indices, only RET-He predicted the future risk of abnormal CSF metabolic profile with a predictive accuracy comparable to serum iron indices. The concordance of homostachydrine and stachydrine changes in serum and CSF indicates their potential use as early biomarkers of brain metabolic dysfunction in infantile ID.

The role of reticulocyte hemoglobin equivalent on the evaluation of iron deficiency and iron deficiency anemia in pediatric cyanotic heart disease: a diagnostic study in Indonesia.

BACKGROUND: In light of prolonged hypoxia, children with cyanotic heart disase (CHD) are at a high risk of developing iron deficiency iron deficiency (ID) and iron deficiency anemia (IDA). Reticulocyte hemoglobin equivalent (Ret-He) is a novel and dependable indicator for assessing iron status. However, there has been no previous study regarding cut-off value in pediatric CHD group. The purpose of this study is to assess the role of Ret-He and to establish cut-off points in the diagnosis of iron deficiency and IDA in pediatric cyanotic heart disease. METHOD: This study was conducted in two tertiary hospitals in Jakarta, Indonesia. 59 children with CHD, aged 3 months to 18 years, were enrolled consecutively. To determine iron status, hematological parameters (hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin) and biochemical parameters for iron status (serum ferritin, transferrin saturation) were analysed and compared to Ret-He levels. The receiver operating characteristic (ROC) analysis was performed for the Ret-He cut-off points for ID and IDA. Sensitivity, specificity, positive and negative predictive value were calculated for each cut-off point. RESULT: Normal iron status was identified in 27 (45.8%) subjects, ID in 8 (13.5%) subjects, and IDA 24 (40.7%) subjects. The ID cut-off value for Ret-He is 28.8 pg (sensitivity 75%, specificity 85.2%, PPV 60%, NPV 92%, and AUC 0.828) and the Ret-He cut-off point for IDA is 28.15 pg (sensitivity 75%, specificity 88.9%, PPV 85.7%, NPV 80%, and AUC 0.824). Hemoglobin should be used in conjunction with Ret-He. ID might be detected in this cohort with Ret-He 28.8 pg and hemoglobin > 16,5 g/dL. While Ret-He 28.15 pg or Ret-He 28.15-28.8 pg with hemoglobin 16.5 g/dL could be used to diagnose IDA. CONCLUSION: The reticulocyte hemolgobin equivalent could be utilised as an iron status parameter in pediatric CHD, with a cut-off value of 28.8 pg for ID and 28.15 pg for IDA.

Enhancing diagnostic accuracy for iron deficiency in pregnant women through mean reticulocyte volume.

BACKGROUND AND OBJECTIVES: Women are more prone to iron deficiency (ID) anemia when pregnant. The diagnostic use of mean reticulocyte volume (MRV) in identifying ID anemia during pregnancy has not been thoroughly investigated. The objective of this study is to evaluate the effectiveness of MRV in diagnosing ID in pregnant women. METHODS AND STUDY DESIGN: Firstly, MRV of 20 healthy female volunteers (healthy group) was measured on specific days for one month. Subsequently, clinical data from 724 pregnant women were thoroughly examined. These women were divided into two groups: 282 with ID (research group) and 442 without ID (control group). Parameters such as MRV, reticulocyte hemoglobin equivalent (RHE), red blood cell volume distribution width-standard deviation (RDW-SD), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), hematocrit (HCT), reticulocyte count (RET), MRV/MCV ratio, and serum ferritin (SF) were analyzed and compared. RESULTS: MRV remained consistent over a period of one month for 20 healthy individuals. In addition, there were significant differences in MRV, RHE, RDW-SD, MCV, MCH, MCHC, HCT, RET, and MRV/MCV between the research group and control group. The receiver operating characteristic (ROC) analysis showed that the areas under the curve (AUCs) for these measures were as follow: 0.840, 0.837, 0.676, 0.654, 0.639, 0.602, 0.571, 0.550, and 0.816, respectively. Ultimately, there was a substantial disparity in MRV prior to and following therapy with oral iron treatments. CONCLUSIONS: In healthy women, MRV remains stable and is a reliable ID marker, which can be used to assess oral iron treatment effectiveness during pregnancy.

Reticulocyte Hemoglobin Equivalent has Comparable Predictive Accuracy as Conventional Serum Iron Indices for Predicting Iron Deficiency and Anemia in a Nonhuman Primate model of Infantile Iron Deficiency.

BACKGROUND: Infantile iron deficiency (ID) causes anemia and compromises neurodevelopment. Current screening relies on hemoglobin (Hgb) determination at 1 year of age, which lacks sensitivity and specificity for timely detection of infantile ID. Low reticulocyte Hgb equivalent (RET-He) indicates ID, but its predictive accuracy relative to conventional serum iron indices is unknown. OBJECTIVES: The objective was to compare diagnostic accuracies of iron indices, red blood cell (RBC) indices, and RET-He for predicting the risk of ID and IDA in a nonhuman primate model of infantile ID. METHODS: Serum iron, total iron binding capacity, unsaturated iron binding capacity, transferrin saturation (TSAT), Hgb, RET-He, and other RBC indices were determined at 2 wk and 2, 4, and 6 mo in breastfed male and female rhesus infants (N = 54). The diagnostic accuracies of RET-He, iron, and RBC indices for predicting the development of ID (TSAT < 20%) and IDA (Hgb < 10 g/dL + TSAT < 20%) were determined using t tests, area under the receiver operating characteristic curve (AUC) analysis, and multiple regression models. RESULTS: Twenty-three (42.6%) infants developed ID and 16 (29.6%) progressed to IDA. All 4 iron indices and RET-He, but not Hgb or RBC indices, predicted future risk of ID and IDA (P < 0.001). The predictive accuracy of RET-He (AUC = 0.78, SE = 0.07; P = 0.003) for IDA was comparable to that of the iron indices (AUC = 0.77-0.83, SE = 0.07; P ≤ 0.002). A RET-He threshold of 25.5 pg strongly correlated with TSAT < 20% and correctly predicted IDA in 10 of 16 infants (sensitivity: 62.5%) and falsely predicted possibility of IDA in only 4 of 38 unaffected infants (specificity: 89.5%). CONCLUSIONS: RET-He is a biomarker of impending ID/IDA in rhesus infants and can be used as a hematological parameter to screen for infantile ID.

Reticulocyte hemoglobin content changes after treatment of anemia of prematurity.

BACKGROUND: Iron deficiency during infancy is associated with poor neurological development, but iron overload causes severe complications. Appropriate iron supplementation is therefore vital. Reticulocyte hemoglobin content (RET-He) provides a real-time assessment of iron status and chracterezes hemoglobin synthesis in preterm infants. However, the existing literature lacks detailed reports assessing chronological changes in RET-He. The aim of this study was to assess the chronological changes in RET-He during oral iron dietary supplementation, and concomitant therapy with recombinant human erythropoietin (rHuEPO) in preterm very low birthweight infants. METHODS: Very low birthweight infants, admitted to our neonatal intensive care unit were analyzed retrospectively. Hemoglobin (Hb), reticulocyte percentage (Ret), mean corpuscular volume, RET-He, serum iron (Fe), and serum ferritin were recorded. Data at birth (T0), the initial day of rHuEPO therapy (T1), the initial day of oral iron supplementation (T2), 1-2 weeks (T3), 3-4 weeks (T4), 5-6 weeks (T5), and 7-8 weeks (T6) from the initial day of oral iron supplementation were extracted, and their changes over time were examined. RESULTS: Reticulocyte hemoglobin content was highest at birth and declined rapidly thereafter, especially after starting rHuEPO therapy. There was no upward trend in RET-He after the initiation of oral iron supplementation, with a slower increase during 5-6 weeks after the initiation of iron therapy. CONCLUSIONS: During the treatment of anemia of prematurity, low RET-He levels may be prolonged. Anemia of prematurity should therefore be assessed and treated on a case-by-case basis, while considering the iron metabolic capacity of preterm infants.

Diagnostic performance of reticulocyte hemoglobin equivalent in assessing the iron status.

BACKGROUND: Measurement of reticulocyte hemoglobin equivalent (RET-He) is rapid, convenient, and cost-effective. Yet, researches on its performance in diagnosing iron deficiency with concurrent inflammation are limited. Hence, this study investigated RET-He value in various states, including inflammation, and evaluated its diagnostic performance in iron status assessment. METHODS: Retrospectively, 953 clinical data and laboratory results-complete blood count, reticulocyte count, RET-He, and serum ferritin-were reviewed. Patients on iron therapy were excluded. Iron status was defined by serum ferritin as the reference method. RET-He among populations was investigated. Its diagnostic performance and optimal cutoff were determined by ROC analysis. RESULTS: Three population groups were classified: healthy control, iron deficiency anemia (IDA), and non-ID anemia. Significantly, RET-He value in IDA was lower than that of healthy control, anemia of inflammation, and chronic kidney disease (P < .0001). Low RET-He was also observed in IDA with concomitant inflammation despite normal-to-high serum ferritin levels. No significant difference was observed between RET-He values in pure IDA and thalassemia (P = .57). ROC curve analysis revealed AUC of 0.876 (P < .0001) at cutoff 30 pg, by which IDA was discriminated with 74.2% sensitivity and 97.4% specificity. Applying cutoff ≤30 pg, IDA can be diagnosed with 96% sensitivity, 97.4% specificity, 80% PPV, and 99.6% NPV. Hence, RET-He >30 pg signifies a non-IDA state. CONCLUSION: In addition to convenience and cost-effectiveness, RET-He cutoff >30 pg can be potentially used to exclude IDA due to its excellent diagnostic sensitivity and specificity.

Significance of Content of the Reticulocyte Hemoglobin in the Management of Renal Anemia.

Optimal iron level in hemodialysis patients remains a subject of debate. The reticulocyte hemoglobin content (CHr) is believed to reflect the concentration of iron required in the most recent hematopoiesis in the bone marrow. CHr is not influenced by any factors that measure direct hemoglobin (Hb) of reticulocytes and is considered a reliable indicator. The supply of iron for Hb synthesis is regulated by hepcidin-25 (Hep-25). However, CHr and Hep-25 measurements are not covered by the Japanese medical insurance system. Serum ferritin (s-ft) and transferrin saturation (TSAT) are used mainly as indicators of internal iron status. Therefore, we examined the relationships among CHr, s-ft, TSAT, and Hep-25 to determine the optimal iron level. This report presents the clinical significance of CHr, the potential use of CHr for the diagnosis of iron deficiency, and tests for optimal iron level using CHr as performed in our hospital.

Reticulocyte hemoglobin equivalent in a thalassemia-prevalent area.

BACKGROUND: Reticulocyte hemoglobin equivalent (Ret-He), a direct measure of the hemoglobin (Hb) in the young red blood cells, has been reported to be useful in the diagnosis of iron deficiency anemia (IDA) but may have some limitations in thalassemia trait. This study evaluated the differences in Ret-He in school-aged children, and assessed the diagnostic value of Ret-He in identifying IDA in a thalassemia-prevalent area. METHODS: Blood samples underwent complete blood count analysis, including Ret-He, ferritin, serum iron and total iron binding capacity. Blood samples also underwent Hb typing and a molecular study for α-thalassemia. Receiver operating characteristic analysis was performed to determine the predictive capacity of Ret-He in the diagnosis of IDA. ID was defined as serum ferritin <30 ng/mL and/or transferrin saturation (TSAT) <16%; IDA was defined as serum ferritin <12 ng/mL and/or TSAT <16% with low Hb for age. Normal healthy children (normal controls: NC) had normal iron study, without the thalassemia trait. RESULTS: Ninety-eight children with a mean age of 12.9 ± 0.6 years were included. Ret-He in the thalassemia trait group (26.7 ± 2.4 pg), ID group (29.0 ± 2.9 pg), IDA group (25.4 ± 2.7 pg), ID + thalassemia trait group (26.6 ± 2.8 pg), and the IDA + thalassemia trait group (24.6 ± 2.3 pg) was significantly lower than in the NC group (30.8 ± 1.7 pg; P < 0.001, 0.01, 0.006, 0.002 and <0.001, respectively). Ret-He had an area under the curve of 0.904 in diagnostic ability for IDA, while a cut-off ≤27 pg had a sensitivity of 91.7% and a specificity of 81%. CONCLUSION: Ret-He was lowest in subjects with IDA + thalassemia trait. A Ret-He cut-off ≤27 pg was suggestive of IDA in the present study.

Reticulocyte Hemoglobin Equivalent (Ret-He) Combined with Red Blood Cell Distribution Width Has a Differentially Diagnostic Value for Thalassemias.

As a type of congenital microcytic hypochromic anemia, thalassemia trait is often confused with other conditions, such as congenital sideroblastic anemia (CSA) and iron deficiency anemia, before a specific work-up is performed. However, these tests, including hemoglobin (Hb) electrophoresis, gene mutations and Prussian blue staining after bone marrow aspirate, are relatively expensive, time-consuming and invasive. To find labor-saving parameters to facilitate differential diagnosis, we retrospectively analyzed the routine blood indexes of 59 thalassemia trait cases [22 α-thalassemia (α-thal), 36 ß-thalassemia (ß-thal) and one α/ß-thal], 21 CSA patients, and 238 iron deficiency anemia controls. Significantly higher reticulocyte Hb equivalent (Ret-He) and lower red blood cell (RBC) distribution width (RDW) were prominent in thalassemia trait. Furthermore, RDW-standard deviation (SD) was independent of the severity of anemia in thalassemia trait, similar to Ret-He in CSA. In the context of the same grades of anemia, Ret-He combined with RDW was powerful in differentiation of thalassemia from CSA and iron deficiency anemia. By receiver operation curve (ROC) analysis, Ret-He had a specificity of 67.06% and a sensitivity of 76.92% with a cutoff value of 20.9 pg for thalassemia trait in mild anemia and a specificity of 84.09% and a sensitivity of 68.42% with a cutoff value of 19.1 pg for thalassemia trait in moderate anemia. Regarding CSA, Ret-He had 92.94% specificity and 60.00% sensitivity in mild anemia, with a cutoff value of 18.1 pg. Overall, Ret-He and RDW are two convenient indexes able to differentiate thalassemia from the other two microcytic anemias, CSA and iron deficiency anemia.

Concordance between Reticulocyte Hemoglobin Equivalent and Reticulocyte Hemoglobin Content in CKD Patients Undergoing Hemodialysis.

AIM: to evaluate the correlation and the concordance between reticulocyte hemoglobin equivalent (RET-He) and reticulocyte hemoglobin content (CHr) as well as to obtain the cut-off value of RET-He as the target of iron supplementation in chronic kidney disease (CKD) patients undergoing hemodialysis. METHODS: a cross-sectional study was performed using K3EDTA-anticoagulated peripheral blood samples collected from 106 CKD patients undergoing routine hemodialysis. The samples were then analyzed using both Sysmex XN-2000 and Siemens ADVIA 2120i for RET-He and CHr analysis. RESULTS: a very strong correlation (r=0.91; p<0.0001) and a good concordance were found between RET-He and CHr with mean bias of 0.5 pg. The diagnostic concordance was 96.23%. The cut-off value of RET-He 29.2 pg was obtained from the receiver operating characteristic (ROC) curve with CHr as the gold standard. At this cut-off point, the sensitivity and specificity to assess the target of iron supplementation in CKD patients undergoing hemodialysis were 95.5% and 94%, respectively. CONCLUSION: the study shows a good correlation and concordance between RET-He and CHr in CKD patients undergoing hemodialysis.

Comparison of reticulocyte hemoglobin equivalent with traditional markers of iron and erythropoiesis in pediatric dialysis.

BACKGROUND: Anemia is a major complication for patients on chronic dialysis. Erythropoietin is effective if iron is available, however unnecessary iron supplementation results in iron overload. Reticulocyte hemoglobin equivalent (Ret-He) may be useful for assessing iron status. METHODS: A national retrospective cohort study including all children on chronic dialysis in New Zealand between 2007 and 2013, pairing Ret-He with demographic information, anemia indices, and markers of iron status. RESULTS: In 606 observations, we found a modest relationship between Ret-He and transferrin saturation (TSAT) (r = 0.34, p < 0.001) and a poor correlation between Ret-He and ferritin (r = 0.09, p = 0.04). There was a negative correlation between ferritin and hemoglobin (r = -0.14, p = 0.002), a weak positive correlation between TSAT and hemoglobin (r = 0.12, p = 0.007), and a modest positive correlation between Ret-He and hemoglobin (r = 0.22, p < 0.001). The diagnostic performance of Ret-He to detect absolute iron deficiency (cut-off value 28.9 pg, sensitivity 90 %, specificity 75 %, AUC 0.87) was good. CONCLUSIONS: Ret-He is a more relevant marker of iron status than ferritin and TSAT. This supports prospectively testing Ret-He to distinguish between iron deficiency and suboptimal erythropoietin dosing as competing causes for anemia. Ferritin is an unhelpful biomarker of iron deficiency in this setting.

Reticulocyte Hemoglobin Content During the First Month of Life in Critically Ill Very Low Birth Weight Neonates Differs From Term Infants, Children, and Adults.

BACKGROUND: Reticulocyte hemoglobin content (RET-He)-an established indicator of iron status in children and adults-was determined in very low birth weight (VLBW) infants. METHODS: Longitudinal retrospective RET-He data in 26 VLBW neonates during the first month of age were compared with: (a) concurrent complete blood counts (CBCs), including hemoglobin (Hb) concentration, reticulocyte count, and immature reticulocyte fraction (IRF), and erythropoietin (EPO) levels; (b) clinical variables; and (c) RET-He data from the literature for term infants, children, and adults. RESULTS: RET-He within 24 hr following birth was 31.8 ± 1.1 pg (mean ± SEM). This was followed by an abrupt, significant decline to 28.3 ± 1.1 pg at 2-4 days, and to steady state levels of 28.4 ± 0.5 pg thereafter. The changes in RET-He were mirrored by changes in plasma EPO, reticulocyte count, and IRF, but not Hb. Steady state RET-He values after 4 days were significantly lower than RET-He values for term infants, children, and adults (31.6 ± 0.11, 32.0 ± 0.12, and 33.0 ± 0.13 pg, respectively). CONCLUSION: Although RET-He values in VLBW infant were lower than term infants, children, and adults, the significance and mechanism(s) responsible are unknown. The present VLBW infant data are relevant to investigations assessing hemoglobinization following treatment with recombinant human EPO (r-HuEPO) and/or iron.

Clinical Value of Hypochromia Markers in the Detection of Latent Iron Deficiency in Nonanemic Premenopausal Women.

BACKGROUND: Iron deficiency (ID) is the most common cause of anemia in fertile women and hemoglobin (Hb) within the reference interval does not exclude ID. The consequence of an imbalance between the iron requirements and supply is a reduction of red-cell Hb content, which causes hypochromic cells. The aim of this study was to assess the reliability of new parameters low Hb density (LHD%), reticulocyte Hb equivalent (RetHe), and percentage of hypochromic erythrocytes (%HypoHe) in the detection of latent ID (LID), defined as depletion of iron stores without anemia. METHODS: Two hundred fifty consecutive nonanemic women in fertile age (18-40 years, mean 33.5 years), whose analyses had been requested by general practitioners, were included. Independent samples t-test, receiver operating characteristic (ROC) curve analysis (gold standard for detecting LID ferritin <30 µg/l), and Cohen's kappa index were applied. RESULTS: One hundred fifty-three women had ferritin within the reference range and Hb >120 g/L; 97 (38.8%) had LID. The results were as follows: %HypoHe-AUC 0.934, cutoff 1.6%, sensitivity 85.7%, specificity 92.1%; RetHe-AUC 0.914, cutoff 29.9 pg, sensitivity 86.8%, specificity 85.7%; LHD%-AUC 0.898, cutoff 5.0%, sensitivity 85.9%, specificity 84.1%. Applying those cutoffs, agreement between ferritin and %HypoHe was κ 0.61 and 0.56 for RetHe and LHD%. CONCLUSIONS: LHD%, %HypoHe, and RetHe emerge as reliable tests for the investigation of LID and could improve the ability to detect ID before anemia is present.

Report of the International Council for Standardization in Haematology working group for standardization of reticulocyte parameters.

INTRODUCTION: The International Council for Standardization in Haematology convened a working group to assess and propose improvements upon the state of standardization and harmonization of reticulocyte parameters among commercial hematology analyzers. METHODS: An international group of laboratory hematologists prospectively collected and analyzed clinical samples using locally available IVD commercial hematology analyzers. Eight hundred and fifty-five total samples were collected at 6 sites using 9 distinct analyzer types. Samples were assessed for reticulocyte percent (RET%), immature reticulocyte fraction (IRF), and reticulocyte hemoglobin content (RHC). Method comparison and regression statistics were calculated. These analyses were used to determine whether statistical recalibration offered a potential avenue for increasing comparability between these methods. RESULTS: While methods producing reticulocyte percent were the most comparable in this study, the state of harmonization for the IRF and RHC was reduced with pearson correlation coefficients ranging from 0.955 to 0.77 and 0.927 and 0.680, respectively. Nevertheless, use of parameters from the Passing Bablok regression substantially improved the comparability of the results. In addition, precision data was derived which also demonstrated substantial differences between analyzer systems. CONCLUSION: While reticulocyte counting is correlated between the automated methods evaluated in this study, the current state of harmonization of other reticulocyte parameters is not as strong. A major challenge in moving this field forward is the need for commutable materials to facilitate comparisons between analyzers not co-located. A potential alternate approach to improve the current state would be instrument re-calibration. However, this is challenging both technically and due to national regulatory frameworks.

Evaluation of hepcidin-25/erythroferrone ratio as a potential biomarker for iron utility and erythropoiesis responsiveness to erythropoiesis-stimulating therapy in comparison to immature erythrocyte/reticulocyte parameters in hemodialysis patients.

BACKGROUND: Anemia-associated chronic kidney disease increases in more advanced stages with a subsequent acceleration in renal impairment progressing to end-stage renal disease. Although hepcidin and erythroferrone have been described as novel biomarkers of iron metabolism, there is still an area of ambiguity regarding iron utility in anemia-associated end-stage renal disease. OBJECTIVES: This study aims to determine the correlations between erythropoietin, erythroferrone, and hepcidin-25 in hemodialysis, and to evaluate the clinical utility of the hepcidin-25/erythroferrone ratio as a biomarker of erythropoiesis-stimulating agent effectiveness compared to reticulocyte maturation parameters. METHODS: Serum erythropoietin, erythroferrone, and hepcidin-25 levels in 35 dialysis-dependent patients on a maintenance dose of a short-acting erythropoiesis-stimulating agent were consequently assessed on Days 0, 5, and 7. The erythropoiesis activity was monitored by measuring the increment in reticulocyte maturation parameters. RESULTS: Though the effectiveness of erythropoiesis in these patients was not associated with the hepcidin-25/erythroferrone ratio, it was lower among those with effective erythropoiesis than those with ineffective erythropoiesis. The effective group showed a statistically significant increase in reticulocyte maturation parameters compared to the ineffective group. CONCLUSIONS: The findings show the pathogenesis of iron homeostasis in hemodialysis, the validity of hepcidin-25/erythroferrone ratio as a biomarker of erythropoiesis-stimulating agent effectiveness, and the advantageous monitoring of reticulocyte maturation measures to improve management of anemia-associated chronic kidney disease.

Reticulocyte hemoglobin content associated with the risk of iron deficiency anemia.

Background/Objective: Reticulocyte hemoglobin content (MCHr) was recognized as a rapid and reliable marker for investigating iron deficiency (ID). We hypothesized that MCHr was associated with the risk of iron deficiency anemia in adults. Methods: This is a dual-center case-control study. A total of 806 patients and healthy individuals were recruited from Ruijin Hospital and Xinhua Hospital affiliated to Shanghai Jiaotong University School of Medicine between January 2021 and December 2021. The participants were categorized into iron deficiency anemia (IDA) group (n = 302), non-IDA group (n = 366), and healthy control group (n = 138). According to the MCHr level, the participants were divided into two groups, i.e. normal MCHr (≥25 pg) and decreased MCHr (<25 pg) group. Multivariate logistic regression analysis and adjusted subgroup analysis were conducted to estimate the relative risk between MCHr and IDA, with confounding factors including age, sex, hemoglobin (Hb), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), Hematocrit (HCT), serum iron (Fe), ferritin (Ferrit), and total iron binding capacity (TIBC). Results: Compared with the non-IDA, the MCHr level with IDA decreased significantly. ROC curve analysis showed that MCHr had the largest area under the AUC curve. After comprehensive adjustment for confounding factors, individuals with normal level of MCHr exhibited a decreased risk of IDA (OR = 0.68 [0.60, 0.77], P < 0.01), while the risk of IDA was up to 5 times higher for those with decreased MCHr. Conclusion: Our findings supported the hypothesis that MCHr was associated with the risk of IDA in adults and could serve as an indicator of IDA severity. MCHr holds clinical value as an auxiliary diagnostic indicator, providing valuable insights into whether invasive examinations are warranted in the assessment of IDA.

Reticulocyte hemoglobin equivalent as a marker to assess iron deficiency: A large pediatric tertiary care hospital study.

INTRODUCTION: Detection of iron deficiency (ID) remains challenging. We aimed to evaluate the performance of reticulocyte hemoglobin equivalent (Ret-He) as a potential diagnostic marker to assess ID and iron deficiency anemia (IDA) in a large pediatric cohort. METHODS: A total of 3158 patients (aged 15 days to 19 years with a median age of 8.5 years; 60.2% female) were retrospectively studied. Statistical analysis was performed (a) to evaluate relationship of Ret-He with other relevant complete blood count and iron panel parameters; (b) to compare the levels of Ret-He in ID and IDA groups to a control group; and (c) to assess sensitivity and specificity of Ret-He in ID, IDA, and anemia without ID groups. RESULTS: Ret-He values were significantly positively correlated to ferritin and transferrin saturation (TSAT). The median Ret-He was significantly lower in ID. A Ret-He cutoff of ≤30.0 pg distinguished cases of ID from the control group with a sensitivity of 90.2%, specificity of 59.5%, and area under curve (AUC) of 0.88. Ret-He showed better diagnostic performance in the IDA group and acceptable performance for ID without anemia. The sensitivity, specificity, and AUC were 90.1%, 80.9%, and 0.93 for IDA at cutoff value of ≤27.4 pg, and 80.8%, 51.1%, and 0.70 for ID without anemia at cutoff value of ≤30.8 pg, respectively. CONCLUSION: Our large pediatric tertiary care hospital study demonstrates that Ret-He is a reliable marker to help confirm IDA in pediatric population. However, further studies are needed for its use to capture the early stages of ID.

Biomarkers of Brain Dysfunction in Perinatal Iron Deficiency.

Iron deficiency in the fetal and neonatal period (perinatal iron deficiency) bodes poorly for neurodevelopment. Given its common occurrence and the negative impact on brain development, a screening and treatment strategy that is focused on optimizing brain development in perinatal iron deficiency is necessary. Pediatric societies currently recommend a universal iron supplementation strategy for full-term and preterm infants that does not consider individual variation in body iron status and thus could lead to undertreatment or overtreatment. Moreover, the focus is on hematological normalcy and not optimal brain development. Several serum iron indices and hematological parameters in the perinatal period are associated with a risk of abnormal neurodevelopment, suggesting their potential use as biomarkers for screening and monitoring treatment in infants at risk for perinatal iron deficiency. A biomarker-based screening and treatment strategy that is focused on optimizing brain development will likely improve outcomes in perinatal iron deficiency.

Clinical significance of reticulocyte hemoglobin content in the diagnosis of iron deficiency anemia.

OBJECTIVE: The aim of this study was to evaluate the clinical significance of reticulocyte hemoglobin content (CHr) in the diagnosis of iron deficiency anemia (IDA) and to compare it with other conventional iron parameters. MATERIALS AND METHODS: A total of 32 female patients with IDA (serum hemoglobin <120 g/L and serum ferritin <20 ng/ mL) and 18 female patients with iron deficiency (serum hemoglobin > 120 g/L and serum ferritin <20 ng/mL) were enrolled. RESULTS: CHr was 24.95±3.92 pg in female patients with IDA and 29.93±2.96 pg in female patients with iron deficiency. CHr showed a significant positive correlation with hemoglobin, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, serum iron, and transferrin saturation and a significant negative correlation with transferrin and total iron-binding capacity. The cut-off value of CHr for detecting IDA was 29 pg. CONCLUSION: Our data demonstrate that CHr is a useful parameter that can be confidently used in the diagnosis of IDA, and a CHr cut-off value of 29 pg predicts IDA. CONFLICT OF INTEREST: None declared.