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.

Iron deficiency in sepsis patients based on reticulocyte hemoglobin and hepcidin concentration: a prospective cohort study.

Introduction: Iron tests are deranged in sepsis; therefore new biomarkers should be used for diagnosis of iron deficiency (ID)/ID anemia (IDA). Methods: Diagnosis of ID/IDA was based on reticulocyte (Ret) hemoglobin (Hb) equivalent (Ret-He) and Hb concentration, with hepcidin (Hep) determined retrospectively. Results: The prevalence of ID and IDA was 7% and 47%, respectively. The AUROCs for Rets number and Hep in prediction of ID/IDA were 0.69 and 0.62, respectively. Conclusions: Approximately half of sepsis patients are iron-deficient. Number of Rets may be a predictor of ID/IDA when Ret-He is not available. Hepcidin is a poor IDA predictor.

Importance of the reticulocyte hemoglobin equivalent in the exclusion of latent iron deficiency.

BACKGROUND: Iron deficiency is an underdiagnosed public health problem, especially in developing countries, that can conceal serious underlying illnesses. Early diagnosis and treatment of latent iron deficiency (LID) is crucial. Reticulocyte hemoglobin equivalent (RET-He), was reported to be a cost-effective tool that reflects the iron availability at erythropoiesis. The aims of this study were to evaluate the RET-He in the exclusion of LID. METHODS: Transversal study was carried out in the laboratory of clinical biology of Ben Arous regional hospital, it included volunteers in apparently good health. We performed a complete blood count and a serum ferritin assay. Participants with normal hemoglobin were divided into two groups: Control group G1: normal ferritin (≥ 15 ng/mL)/LID group G2: low ferritin (< 15 ng/mL). We compared the blood count parameters of the two groups. RESULTS: We selected 108 participants (G1: 88 (81.5%), G2: 20 (18.5%)), mean age = 36 years, gender-ratio = 0.92. We noted, in G2, significantly lower rates for hemoglobin Hb (p < 0.001), hematocrit (p < 0.001), mean corpuscular hemoglobin MCH (p = 0.026), reticulocyte count (p = 0.039) and RET-He (p < 0.001) and significantly higher rate for RDW/CV (p = 0.009). RET-He averages were 29.1 pg in G2 and 31.1pg in G1. In multivariate analysis, only RET-He showed a significant difference between the two groups. Area under the curve was 0.872, the cutoff = 30.9 (sensitivity 100%, specificity 61%, PPV 37%, NPV 100%). CONCLUSION: RET-He is an accessible and affordable parameter of the iron status, with an excellent NPV. It would be interesting to evaluate our results on a larger sample to define reference values in our population.

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-Equivalent Potentially Detects, Diagnoses and Discriminates between Stages of Iron Deficiency with High Sensitivity and Specificity.

Background: Iron deficiency anemia (IDA) is a global health problem affecting the quality of life of more than 2 billion individuals. The current practice guidelines diagnose and monitor IDA via conventional hematological and iron biomarkers, which take several months before they are corrected under an iron-treatment plan. Reticulocyte hemoglobin equivalent (Ret-He) is used as a marker in most new hematology analyzers to assess iron incorporation into erythrocyte hemoglobin directly. This study aims to examine the efficacy of Ret-He as a marker for iron deficiency (ID) and IDA and investigate whether Ret-He is sensitive to iron therapy. Methods: Two blood samples were drawn from 182 participants for CBC and iron profile measurements. Follow-up samples were drawn from participants with a confirmed diagnosis of ID and/or IDA. Results: Ret-He levels were lower in the ID and IDA groups compared to the control (p < 0.0001), and lower in the IDA group compared to the ID group (p < 0.0001). Ret-He was correlated with ferritin at ID level (<30.0 mg/mL; r = 0.39) and severe IDA (<13.0 ng/mL; p-value < 0.01, r = 0.57). Cut-off values of <28.25 pg for ID and <21.55 pg for IDA showed a higher specificity and sensitivity (ID; AUC: 0.99, sensitivity: 92.73%, specificity: 97.87%) and (IDA; AUC: 0.94, sensitivity: 90.63%, specificity: 92.31%). Finally, Ret-He successfully reflected the iron therapy (p < 0.001) when compared to hemoglobin (Hb) (p = 0.1). Conclusions: Ret-He is a potential marker for detecting and diagnosing different stages of ID with high validity and is very sensitive in reflecting the iron incorporation in a short time.

The Reticulocyte Hemoglobin Equivalent as a Screening Marker for Iron Deficiency and Iron Deficiency Anemia in Children.

BACKGROUND: Iron deficiency (ID) is one of the most common nutritional deficiencies in children worldwide and may result in iron deficiency anemia (IDA). The reticulocyte hemoglobin equivalent (Ret-He) provides information about the current availability of iron in erythropoiesis. This study aims to examine the validation of Ret-He as a screening marker for ID and IDA in children. METHODS: Blood samples were retrospectively obtained from medical records. Anemia was defined according to the definition provided by the World Health Organization (WHO) for children. ID was defined by transferrin saturation (TSAT) < 20% and ferritin < 100 ng/mL. Children were classified into four groups: IDA, non-anemia iron deficiency (NAID), control and others. RESULTS: Out of 970 children, 332 (34.2%) had NAID and 278 (28.7%) presented with IDA. Analysis revealed that Ret-He significantly correlates with ferritin (rho = 0.41; p < 0.001), TSAT (rho = 0.66; p < 0.001) and soluble transferrin receptor (sTfR) (rho = -0.72; p < 0.001). For ROC analysis, the area under the curve (AUC) was 0.771 for Ret-He detecting ID and 0.845 for detecting IDA. The cut-off value for Ret-He to diagnose ID was 33.5 pg (sensitivity 90.7%; specificity 35.8%) and 31.6 pg (sensitivity 90.6%; specificity 50.4%) to diagnose IDA. CONCLUSIONS: The present study demonstrates Ret-He to be a screening marker for ID and IDA in children. Furthermore, Ret-He can be used as a single screening parameter for ID and IDA in children without considering other iron parameters. Economically, the use of Ret-He is highly relevant, as it can save one blood tube per patient and additional costs.

Reticulocyte Hemoglobin Equivalent in Patients with Idiopathic Warm Autoimmune Hemolytic Anemia: Implication in the Development of Macrocytosis.

OBJECTIVE: Patients with warm autoimmune hemolytic anemia (WAIHA) present with anemia that is highly heterogeneous, and often have macrocytic anemia with inappropriately elevated mean corpuscular volume (MCV). The goal of this retrospectivecase study is to elucidate the characteristics of anemia in patients with idiopathic WAIHA. PROCEDURES: The hematological parameters were analyzed by automated hematology analyzers in 19 consecutive patients with idiopathic WAIHA. Thecontent of hemoglobin (Hb) in the reticulocytes was assessed as reticulocyte Hb equivalent (RET-He). Relevant laboratory data and medical records were retrospectively studied. RESULTS: The median MCV was 102.7 fL and ten patients had macrocytic anemia with MCV above 100 fL. There was a significant correlation between the percentage of reticulocytes and MCV. The median RET-He value was 35.9 pg, and the reticulocytes of patients with higher MCV had higher RET-He. There was a significant correlation between red cell volume distribution width (RDW) andMCV, while the association between RDW and RET-He was not significant. Red blood cell agglutination was not seen in any of the patients. Relative folate deficiency was implied to contribute to the increased Hb content in the reticulocytes of WAIHA patients. CONCLUSION: Reticulocytes in WAIHA patients often contain more Hb than normal reticulocytes and become inappropriately large, possibly due to relative folate deficiency. Elevated MCV in WAIHA patients is due to the increase in both the number and the Hb content of reticulocytes.

Utilidad clínica del equivalente de hemoglobina reticulocitaria en niños en hemodiálisis / Clinical usefulness of the reticulocyte hemoglobin equivalent in children on hemodialysis

Introducción. La anemia por deficiencia de hierro en hemodiálisis es frecuente. Para su detección se utiliza la ferritina sérica y la saturación de transferrina (ST). El equivalente de hemoglobina reticulocitaria (RET-He) es un análisis que no se modifica en estados inflamatorios y refleja directamente el hierro disponible en médula ósea.Objetivo. Explorar la capacidad diagnóstica de deficiencia absoluta de hierro del RET-He y evaluar su correlación con marcadores tradicionales de ferropenia.Población y métodos. Estudio retrospectivo que comparó RET-He con ferritina y ST en niños en hemodiálisis atendidos en el Hospital Garrahan entre julio de 2016 y julio de 2019. Resultados. En 164 observaciones realizadas en 40 niños, se encontró correlación positiva débil entre hemoglobina y RET-He (r 0,35, p < 0,001), positiva significativa entre ST y RET-He (r 0,52, p < 0,001), negativa baja entre hemoglobina y ferritina (r -0,19, p 0,02) y ausencia de correlación entre hemoglobina y ST (r 0,05, p 0,5). El 50 % presentaba anemia; la ferropénica fue por marcadores tradicionales en el 13 % y por RET-He en el 44 %. El RET-He mostró sensibilidad del 90,9 % (IC 95: 57,1-99,5 %), especificidad del 74,5 % (IC 95: 66,7-81 %), valor predictivo negativo del 99,1 % (IC 95: 94,5-99,9 %) y positivo del 20,4 % (IC 95: 10,7-34,7 %) para detectar anemia ferropénica con valor de corte de 29 picogramos.Conclusiones. Pese a su capacidad limitada, el RET-He como biomarcador de deficiencia de hierro aumenta la detección de anemia ferropénica en niños en hemodiálisis

Introduction. Iron-deficiency anemia is common in hemodialysis patients. Serum ferritin and transferrin saturation (TS) are used for its detection. The reticulocyte hemoglobin equivalent (RET-He) is a marker that is not altered by inflammatory conditions and directly reflects iron availability in the bone marrow.Objective. To explore the diagnostic capability of RET-He to detect absolute iron deficiency and assess its correlation with traditional markers of iron deficiency.Population and methods. Retrospective study comparing RET-He with ferritin and TS in children on hemodialysis seen at Hospital Garrahan between July 2016 and July 2019.Results. In 164 observations carried out in 40 children, a weak positive correlation was found between hemoglobin and RET-He (r = 0.35, p < 0.001), a significant positive correlation between TS and RET-He (r = 0.52, p < 0.001), a low negative correlation between hemoglobin and ferritin (r = -0.19, p = 0.02), and a lack of correlation between hemoglobin and TS (r = 0.05, p = 0.5). Anemia was observed in 50 %; iron-deficiency anemia was detected by traditional markers in 13 % and by RET-He in 44 %. RET-He showed a sensitivity of 90.9 % (95 % CI: 57.1-99.5 %), a specificity of 74.5 % (95 % CI: 66.7-81 %), a negative predictive value of 99.1 % (95 % CI: 94.5-99.9 %), and a positive predictive value of 20.4 % (95 % CI: 10.7-34.7 %) to detect iron-deficiency anemia with a cut-off value of 29 pg.Conclusions. Despite its limited capability, the use of RET-He as a biomarker of iron deficiency increases the detection of iron-deficiency anemia in children on hemodialysis.

Clinical usefulness of the reticulocyte hemoglobin equivalent in children on hemodialysis. / Utilidad clínica del equivalente de hemoglobina reticulocitaria en niños en hemodiálisis.

INTRODUCTION: Iron-deficiency anemia is common in hemodialysis patients. Serum ferritin and transferrin saturation (TS) are used for its detection. The reticulocyte hemoglobin equivalent (RET-He) is a marker that is not altered by inflammatory conditions and directly reflects iron availability in the bone marrow. OBJECTIVE: To explore the diagnostic capability of RET-He to detect absolute iron deficiency and assess its correlation with traditional markers of iron deficiency. POPULATION AND METHODS: Retrospective study comparing RET-He with ferritin and TS in children on hemodialysis seen at Hospital Garrahan between July 2016 and July 2019. RESULTS: In 164 observations carried out in 40 children, a weak positive correlation was found between hemoglobin and RETHe (r = 0.35, p < 0.001), a significant positive correlation between TS and RET-He (r = 0.52, p < 0.001), a low negative correlation between hemoglobin and ferritin (r = -0.19, p = 0.02), and a lack of correlation between hemoglobin and TS (r = 0.05, p = 0.5). Anemia was observed in 50 %; iron-deficiency anemia was detected by traditional markers in 13 % and by RET-He in 44 %. RET-He showed a sensitivity of 90.9 % (95 % CI: 57.1-99.5 %), a specificity of 74.5 % (95 % CI: 66.7-81 %), a negative predictive value of 99.1 % (95 % CI: 94.5-99.9 %), and a positive predictive value of 20.4 % (95 % CI: 10.7-34.7 %) to detect iron-deficiency anemia with a cut-off value of 29 pg. CONCLUSIONS: Despite its limited capability, the use of RET-He as a biomarker of iron deficiency increases the detection of iron-deficiency anemia in children on hemodialysis.

Introducción. La anemia por deficiencia de hierro en hemodiálisis es frecuente. Para su detección se utiliza la ferritina sérica y la saturación de transferrina (ST). El equivalente de hemoglobina reticulocitaria (RET-He) es un análisis que no se modifica en estados inflamatorios y refleja directamente el hierro disponible en médula ósea. Objetivo. Explorar la capacidad diagnóstica de deficiencia absoluta de hierro del RETHe y evaluar su correlación con marcadores tradicionales de ferropenia. Población y métodos. Estudio retrospectivo que comparó RET-He con ferritina y ST en niños en hemodiálisis atendidos en el Hospital Garrahan entre julio de 2016 y julio de 2019. Resultados. En 164 observaciones realizadas en 40 niños, se encontró correlación positiva débil entre hemoglobina y RET-He (r 0,35, p < 0,001), positiva significativa entre ST y RET-He (r 0,52, p < 0,001), negativa baja entre hemoglobina y ferritina (r -0,19, p 0,02) y ausencia de correlación entre hemoglobina y ST (r 0,05, p 0,5). El 50 % presentaba anemia; la ferropénica fue por marcadores tradicionales en el 13 % y por RETHe en el 44 %. El RET-He mostró sensibilidad del 90,9 % (IC 95: 57,1-99,5 %), especificidad del 74,5 % (IC 95: 66,7-81 %), valor predictivo negativo del 99,1 % (IC 95: 94,5-99,9 %) y positivo del 20,4 % (IC 95: 10,7-34,7 %) para detectar anemia ferropénica con valor de corte de 29 picogramos. Conclusiones. Pese a su capacidad limitada, el RET-He como biomarcador de deficiencia de hierro aumenta la detección de anemia ferropénica en niños en hemodiálisis.

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.

The Importance of RET-He in the Diagnosis of Iron Deficiency and Iron Deficiency Anemia and the Evaluation of Response to Oral Iron Therapy.

BACKGROUND: The purpose of this study is to investigate whether or not reticulocyte hemoglobin equivalent (RET-He) is a superior indicator of blood count and other iron parameters in terms of diagnosing iron deficiency (ID) and iron deficiency anemia (IDA), and thus evaluating a patient's response to oral iron treatment. METHODS: The research population consisted of 217 participants in total: 54 control, 53 ID, 58 non-ID anemia, and 52 IDA patients. A hemoglobin (Hb) value of < 130.0 g/L was defined as indicating anemia for men, while an Hb value of < 120.0 g/L was defined as indicating anemia for women. All patients were administered 270 mg oral elemental iron sulphate daily. RESULTS: The RET-He was significantly lower in the IDA group, compared to other groups (IDA: 21.0 ± 4.1, ID: 26.0 ± 4.9, non-ID anemia: 32.1 ± 6.8, control: 36.6 ± 7.0; < 0.001). The ID group had a lower RET-He compared to the non-ID anemia group and the control group. On the 5th day of treatment, the ID and IDA group showed no significant differences in terms of Hb while the RET-He level demonstrated a significant increase. The increase in the RET-He level observed in the IDA group on the 5th day was significantly higher compared to the increase observed in the ID group. A RET-He value of 25.4 pg and below predicted ID diagnosis with 90.4% sensitivity and 49.1% specificity in IDA patients, compared to the ID group. CONCLUSIONS: The results of our study, therefore, suggest that RET-He may be a clinically useful marker in the diagnosis of ID and IDA.

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.

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.

Reticulocyte hemoglobin equivalent as a potential marker for diagnosis of iron deficiency.

Evaluation of parameters relating to serum ferritin and iron is critically important in the diagnosis of iron deficiency anemia (IDA). The recent development of automated systems for hematology analysis has made it possible to measure reticulocyte hemoglobin equivalent (RET-He), which is thought to reflect iron content in reticulocytes, in the same sample used for complete blood count tests. If RET-He is, indeed, capable of evaluating iron deficiency (ID), it would be useful for immediate diagnosis of IDA. In the present study, we examined the usefulness of RET-He for diagnosis of ID. Blood samples were obtained from 211 patients. Anemia was defined as hemoglobin (Hb) level of <12 g/dL. Iron deficiency was defined as serum ferritin level of <12 ng/mL. Patients were classified into four groups: IDA, ID, control, and non-ID with anemia. Patients in the IDA group had significantly lower RET-He levels than those in the control group. RET-He correlated with serum ferritin in the IDA and ID groups. The area under the curve for RET-He was 0.902, indicating that RET-He facilitates the diagnosis of ID with high accuracy. RET-He changed in parallel with changes in Hb during iron administration for 21 IDA patients. Our results indicate that RET-He may be a clinically useful marker for determining ID in the general population.

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.

Acceleration of iron utilization after intravenous iron administration during activated erythropoiesis in hemodialysis patients: a randomized study.

This study aimed to evaluate the effect of different timings of iron administration during erythropoiesis activated by continuous erythropoietin receptor activator (CERA) on reticulocyte iron uptake in hemodialysis patients. In total, 110 patients were randomized to receive 40 mg intravenous elemental iron doses at all three hemodialysis sessions in the first week (IW1 group: n = 57) or in the third week (IW3 group: n = 53) after CERA administration. Following CERA administration at day 0, reticulocyte count increased, peaking at day 7. At days 7 and 14, the observed changes in Ret-He were higher in the IW1 group than in the IW3 group. Increases in total reticulocyte hemoglobin at day 7 were higher in the IW1 group than in the IW3 group. In contrast, there was only tendency toward greater total reticulocyte hemoglobin after iron administration in the third week in the IW3 group. Intravenous iron supplementation in the first week of CERA administration increases reticulocyte iron uptake; however, iron supplementation in the third week does not. The findings indicate that iron should be intravenously administered to increase the efficacy of CERA within 1 week of CERA administration during highly active erythropoiesis.