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Keywords = reticulocyte hemoglobin (Ret He)

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12 pages, 736 KB  
Article
The Role of Reticulocyte-Derived Parameters in the Detection of Iron-Restricted Erythropoiesis in the Elderly
by Eloísa Urrechaga and Mónica Fernández
Diagnostics 2026, 16(6), 928; https://doi.org/10.3390/diagnostics16060928 - 20 Mar 2026
Viewed by 572
Abstract
Background: Mindray BC-6800 Plus TM (Mindray, Shenzhen, China) measures reticulocyte counts and provides the reticulocyte hemoglobin (RHe, reticulocyte Hb expression) and mean reticulocyte volume (MRV). We studied the performance of those reticulocyte-derived parameters for the detection of iron-restricted erythropoiesis in older patients, [...] Read more.
Background: Mindray BC-6800 Plus TM (Mindray, Shenzhen, China) measures reticulocyte counts and provides the reticulocyte hemoglobin (RHe, reticulocyte Hb expression) and mean reticulocyte volume (MRV). We studied the performance of those reticulocyte-derived parameters for the detection of iron-restricted erythropoiesis in older patients, compared with standard laboratory tests. Methods: A total of 220 anemic patients, age > 65 years, were recruited in the context of routine health controls. Group differences were assessed using analysis of variance (ANOVA), with p values < 0.05 considered statistically significant. Receiver operating characteristic (ROC) curve analysis was performed to assess the diagnostic performance of RHe and MRV for detecting iron-restricted erythropoiesis. The reference standard for iron deficiency was sTfR > 52 nmol/L. A multivariable logistic regression model was constructed for iron-restricted erythropoiesis, including MRV, Ret-He and s-ferritin as independent covariates, and adjusted for inflammatory status and renal function. Results: Overall, 30.1% in the group had IDA and 29.0% had mixed IDA/ACD, so 59.1% had absolute or functional iron deficiency, while 40.9% had adequate iron supply. RHe and MRV values differed significantly between both groups (p = 0.0001). For s-ferritin, ROC analysis yielded an AUC of 0.685 (95% CI 0.606–0.767), with the best Youden index at a cut-off of 100 µg/L, corresponding to 72.5% sensitivity and 65.9% specificity. An MRV cut-off of 97.4 fL identified iron-restricted erythropoiesis with 88.2% sensitivity and 82.7% specificity (AUC 0.878, 95% CI 0.799–0.957); RHe AUC 0.860, 95% CI 0.777–0.947; cut-off 30.4 pg; sensitivity 82.4%, specificity 79.8%). In multivariable logistic regression adjusted for CRP and eGFR, s-ferritin was not an independent predictor of iron-restricted erythropoiesis, whereas MRV and RHe remained significant. The overall model demonstrated good discrimination, with an AUC 0.808 (95% CI 0.804–0.814). Conclusions: RHe and MRV are reliable parameters for assessing iron supply to erythropoiesis in older patients and can assist in distinguishing iron-restricted erythropoiesis in complex, inflammation-driven settings. Full article
(This article belongs to the Special Issue Advances in Hematology Laboratory—2nd Edition)
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12 pages, 563 KB  
Article
Iron Deficiency Prevention, Screening, and Treatment: A Quality Improvement Initiative Introducing Reticulocyte Hemoglobin in a Level III Neonatal Intensive Care Unit
by Narmin Javadova, Pamela J. Kling, Sally Norlin and Whitley N. Hulse
Nutrients 2025, 17(21), 3391; https://doi.org/10.3390/nu17213391 - 29 Oct 2025
Cited by 1 | Viewed by 2429
Abstract
Objective: To implement a neonatal iron deficiency (ID) guideline as part of a neuroprotective strategy using reticulocyte hemoglobin content (RET-He) for neonates born <33 weeks postmenstrual age (PMA) and small for gestational age (SGA) neonates ≥33 weeks PMA, to achieve ≥80% screening [...] Read more.
Objective: To implement a neonatal iron deficiency (ID) guideline as part of a neuroprotective strategy using reticulocyte hemoglobin content (RET-He) for neonates born <33 weeks postmenstrual age (PMA) and small for gestational age (SGA) neonates ≥33 weeks PMA, to achieve ≥80% screening rate by June 2024. Methods: An interdisciplinary team conducted a quality improvement initiative in a level III neonatal intensive care unit (NICU) from April 2022 to August 2024. RET-He is a validated, sensitive marker of early iron deficiency reflecting recent iron supply for erythropoiesis and providing a more reliable measure than ferritin. The primary outcome was RET-He screening at 30 ± 7 days for neonates <33 weeks PMA or pre-discharge for SGA neonates ≥33 weeks PMA. Exclusion criteria were death or transfer before eligibility. Process measures included ID screening failure rate (RET-He level < 29 pg). Results: Of 345 eligible neonates, P-chart analysis showed screening rates for premature neonates <33 weeks PMA declined during PDSA 1–2, before improving to 85.9% in PDSA 3. ID screening failure was 12.6% at one month, increasing to 32.1% at two months. For SGA neonates ≥33 weeks PMA, screening rates remained low, peaking at 36% in PDSA 3, with a 2.2% failure rate. Conclusions: Implementation of a RET-He based ID guideline improved screening rates for premature neonates but was less effective for SGA neonates. Despite improved guideline adherence, ID prevalence remained high at NICU discharge, indicating a further need to improve nutritional prevention and treatment strategies. Full article
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10 pages, 531 KB  
Article
Comparison of Standard and New Iron Status Biomarkers: A Prospective Cohort Study in Sepsis Patients
by Piotr F. Czempik and Agnieszka Wiórek
Healthcare 2023, 11(7), 995; https://doi.org/10.3390/healthcare11070995 - 30 Mar 2023
Cited by 7 | Viewed by 3686
Abstract
Both iron deficiency (ID) and iron overload can have negative effects on the risk and course of infection. Therefore, the ability to accurately assess iron status in these patients is of the utmost importance. Systemic inflammation in sepsis patients affects the results of [...] Read more.
Both iron deficiency (ID) and iron overload can have negative effects on the risk and course of infection. Therefore, the ability to accurately assess iron status in these patients is of the utmost importance. Systemic inflammation in sepsis patients affects the results of standard iron biomarkers and makes accurate diagnosis of ID problematic. The aim of our study was to analyze the association between widely available standard iron biomarkers and selected new iron biomarkers in various iron status subgroups among sepsis patients. Consecutive patients diagnosed with sepsis or septic shock and procalcitonin concentration > 0.5 ng/mL were enrolled. The following iron biomarkers were determined: iron, ferritin, transferrin, transferrin saturation, reticulocyte (Ret) number and percentage, Ret hemoglobin equivalent, Ret fluorescence subpopulations, and hepcidin concentration. The study group comprised 90 study subjects. There were 42 (47%) patients with normal iron status, 6 (6%) with ID without anemia, and 42 (47%) with ID anemia. No meaningful correlation exists between standard and new iron biomarkers in various iron status subgroups among sepsis patients. Therefore, standard iron biomarkers cannot be used to diagnose ID in this cohort. Full article
(This article belongs to the Special Issue Hematologic Challenges in Anesthesiology and Critical Care)
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11 pages, 458 KB  
Article
Reticulocyte Hemoglobin as a Screening Test for Iron Deficiency Anemia: A New Cut-Off
by Abdullah I. Aedh, Mohamed S. M. Khalil, Alaa S. Abd-Elkader, Mohamed M. El-Khawanky, Hamdan M. Alshehri, Amr Hussein, Ali A. Lafi Alghamdi and Abdulkarim Hasan
Hematol. Rep. 2023, 15(1), 201-211; https://doi.org/10.3390/hematolrep15010021 - 14 Mar 2023
Cited by 16 | Viewed by 12862
Abstract
Introduction: Latent iron deficiency (LID), in which iron stores in the body are depleted without incidental anemia, poses a key diagnostic challenge. Reticulocyte hemoglobin content (Ret-Hb) is directly correlated with the functionally available iron for heme synthesis in erythroblasts. Consequently, Ret-Hb has been [...] Read more.
Introduction: Latent iron deficiency (LID), in which iron stores in the body are depleted without incidental anemia, poses a key diagnostic challenge. Reticulocyte hemoglobin content (Ret-Hb) is directly correlated with the functionally available iron for heme synthesis in erythroblasts. Consequently, Ret-Hb has been proposed as an efficient iron status marker. Aim: To assess the importance of Ret-Hb in detecting latent iron deficiency as well as its use in screening for iron deficiency anemia. Materials and Methods: A study involving 108 individuals was conducted at Najran University Hospital, 64 of whom had iron deficiency anemia (IDA) and 44 of whom had normal hemoglobin levels. All patients were subjected to complete blood count (CBC), reticulocyte percentage, Ret-Hb, serum iron, total iron binding capacity (TIBC), and serum ferritin measurements. Results: A significant decrease in Ret-Hb level was observed in IDA patients compared to non-anemic individuals, with a cut-off value of 21.2 pg (a value below which indicates IDA). Conclusion: The measurement of Ret-Hb, in addition to CBC parameters and indices, provides an accessible predictive marker for both iron deficiency (ID) and IDA. Lowering the Ret-Hb cut-off could better allow for its use as a screening parameter for IDA. Full article
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13 pages, 1556 KB  
Article
Improved Diagnosis of Iron Deficiency Anemia in the Critically Ill via Fluorescence Flowcytometric Hemoglobin Biomarkers
by Mascha Zuther, Marie-Luise Rübsam, Mathias Zimmermann, Alexander Zarbock and Christian Hönemann
Cells 2023, 12(1), 140; https://doi.org/10.3390/cells12010140 - 29 Dec 2022
Cited by 13 | Viewed by 4817
Abstract
Background: Iron deficiency anemia (IDA) is common in critically ill patients treated in the intensive care unit (ICU), and it can lead to severe consequences. Precise and immediate diagnostics are not available, but they are inevitably needed to administer adequate therapy. Serological parameters [...] Read more.
Background: Iron deficiency anemia (IDA) is common in critically ill patients treated in the intensive care unit (ICU), and it can lead to severe consequences. Precise and immediate diagnostics are not available, but they are inevitably needed to administer adequate therapy. Serological parameters such as serum ferritin and transferrin saturation (TSAT) are heavily influenced by simultaneous inflammation reactions, resulting in the need for more suitable parameters. Reticulocyte biomarkers such as reticulocyte hemoglobin content (RET-He) and Delta-hemoglobin equivalent (Delta-He) determined by fluorescence flowcytometry are more specific for the diagnosis of IDA-based anemia and should be investigated for this purpose. Methods: In a prospective cohort single-center study, serum ferritin and transferrin saturation (TSAT) were collected and compared to RET-He and Delta-He by performing a receiver operating curve (ROC) analysis. The sensitivity and specificity of a single variable or the combination of two variables, as well as cutoff values, for the diagnosis of IDA were calculated. A group comparison for IDA patients without IDA was performed for a control group. Results: A total of 314 patients were enrolled from an interdisciplinary ICU. RET-He (area under the curve (AUC) 0.847) and Delta-He (AUC 0.807) did indicate iron-deficient anemia that was more specific and sensitive in comparison to serum ferritin (AUC 0.678) and TSAT (AUC 0.754). The detection of functional iron deficiency (FID) occurred in 28.3% of cases with anemia. Conclusions: Determination of RET-He and Delta-He allows for the increased precision and sensitivity of iron-deficient anemia in the ICU. Full article
(This article belongs to the Special Issue Biomarkers and Cellular Biology in Perioperative Medicine)
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12 pages, 1473 KB  
Article
Prevalence and Implications of Low Reticulocyte–Hemoglobin Levels among Extreme Preterm Neonates: A Single-Center Retrospective Study
by Jhanahan Sriranjan, Christine Kalata, Gerhard Fusch, Karen Thomas and Ipsita Goswami
Nutrients 2022, 14(24), 5343; https://doi.org/10.3390/nu14245343 - 16 Dec 2022
Cited by 4 | Viewed by 3738
Abstract
This retrospective cohort study aims to determine the epidemiology of iron deficiency among extreme preterm neonates and the association of iron-deficient status during the NICU stay with neurodevelopmental outcomes at 18–24 months. Neonates ≤29 weeks gestational age (GA) born between June 2016 and [...] Read more.
This retrospective cohort study aims to determine the epidemiology of iron deficiency among extreme preterm neonates and the association of iron-deficient status during the NICU stay with neurodevelopmental outcomes at 18–24 months. Neonates ≤29 weeks gestational age (GA) born between June 2016 and December 2019, who received routine iron supplementation were enrolled. Iron deficiency was defined as reticulocyte–hemoglobin (Ret-Hb) levels ≤ 29 pg at 36 weeks corrected age. A subcohort of neonates completed standardized developmental assessment at 18–24 months corrected age. Significant neurodevelopmental impairment (sNDI) was defined as either Bayley Scales of Infant Development score < 70 or cerebral palsy or blindness or hearing aided. Among a cohort of 215 neonates [GA 25.8 (1.7) weeks, birthweight 885 (232) g], prevalence of iron deficiency was 55%, 21%, 26%, and 13%, in neonates <24 weeks, 24–25 + 6 weeks, 26–27 + 6 weeks, and ≥ 28 weeks GA, respectively. Male sex and receipt of corticosteroid therapy were associated with iron-deficiency. In the subcohort analysis (n = 69), there was no statistically significant association between Ret-Hb levels at 36 weeks corrected age and the risk of sNDI [OR 0.99 (95% CI 0.85–1.2)]. Male infants and those who received postnatal corticosteroids are likely to have iron-limited erythropoiesis at corrected term despite routine iron-supplementation; however, low Ret-Hb levels during the neonatal period were not associated with significant neurological disability in early childhood. Full article
(This article belongs to the Special Issue Biomarkers of Nutritional Exposure and Nutritional Status)
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11 pages, 1384 KB  
Article
Reticulocyte Hemoglobin-Equivalent Potentially Detects, Diagnoses and Discriminates between Stages of Iron Deficiency with High Sensitivity and Specificity
by Majed N. Almashjary, Ahmed S. Barefah, Salem Bahashwan, Ibraheem Ashankyty, Refaat ElFayoumi, Majed Alzahrani, Duaa M. Assaqaf, Raghad S. Aljabri, Amera Y. Aljohani, Rema Muslim, Sara A. Baawad, Waleed M. Bawazir and Saif A. Alharthy
J. Clin. Med. 2022, 11(19), 5675; https://doi.org/10.3390/jcm11195675 - 26 Sep 2022
Cited by 14 | Viewed by 7407
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Topic Biochemical and Biophysical Properties of Red Blood Cells)
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12 pages, 1414 KB  
Review
Reticulocyte and Erythrocyte Hemoglobin Parameters for Iron Deficiency and Anemia Diagnostics in Patient Blood Management. A Narrative Review
by Christian Hoenemann, Norbert Ostendorf, Alexander Zarbock, Dietrich Doll, Olaf Hagemann, Mathias Zimmermann and Markus Luedi
J. Clin. Med. 2021, 10(18), 4250; https://doi.org/10.3390/jcm10184250 - 19 Sep 2021
Cited by 29 | Viewed by 9923
Abstract
Anemia, iron deficiency and other hematinic deficiencies are a major cause of perioperative transfusion needs and are associated with increased morbidity and mortality. Anemia can be caused either by decreased production of hemoglobin or red blood cells or by increased consumption and blood [...] Read more.
Anemia, iron deficiency and other hematinic deficiencies are a major cause of perioperative transfusion needs and are associated with increased morbidity and mortality. Anemia can be caused either by decreased production of hemoglobin or red blood cells or by increased consumption and blood loss. Decreased production can involve anything from erythropoietin or vitamin B12 insufficiency to absolute or functional lack of iron. Thus, to achieve the goal of patient blood management, anemia must be addressed by addressing its causes. The traditional parameters to diagnose anemia, despite offering elaborate options, are not ideally suited to giving a simple overview of the causes of anemia, e.g., iron status for erythropoiesis, especially during the acute phase of inflammation, acute blood loss or iron deficiency. Reticulocyte hemoglobin can thus help to uncover the cause of the anemia and to identify the main factors inhibiting erythropoiesis. Regardless of the cause of anemia, reticulocyte hemoglobin can also quickly track the success of therapy and, together with the regular full blood count it is measured alongside, help in clearing the patient for surgery. Full article
(This article belongs to the Special Issue Interdisciplinary Intensive Care)
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12 pages, 1332 KB  
Article
The Reticulocyte Hemoglobin Equivalent as a Screening Marker for Iron Deficiency and Iron Deficiency Anemia in Children
by Vanessa Neef, Elke Schmitt, Peter Bader, Frank Zierfuß, Gudrun Hintereder, Andrea U. Steinbicker, Kai Zacharowski and Florian Piekarski
J. Clin. Med. 2021, 10(16), 3506; https://doi.org/10.3390/jcm10163506 - 9 Aug 2021
Cited by 15 | Viewed by 7419
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Section Anesthesiology)
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4 pages, 646 KB  
Article
Effects of Iron Supplementation on Red Blood Cell Hemoglobin Content in Pregnancy
by Margreet Schoorl, Marianne Schoorl, Derek van der Gaag and Piet C.M. Bartels
Hematol. Rep. 2012, 4(4), e24; https://doi.org/10.4081/hr.2012.e24 - 28 Nov 2012
Cited by 27
Abstract
Although a mild degree of anemia is common in the third trimester of pregnancy, it remains a challenge to establish whether a decrease in hemoglobin (Hb) concentration is physiological or pathological. The World Health Organization suggested a Hb concentration of 110 g/L to [...] Read more.
Although a mild degree of anemia is common in the third trimester of pregnancy, it remains a challenge to establish whether a decrease in hemoglobin (Hb) concentration is physiological or pathological. The World Health Organization suggested a Hb concentration of 110 g/L to discriminate anemia. Several European investigators recommended Hb cut-off values of between 101–110 g/L. The aim of this study was to establish short-term effects of iron supplementation on the hemoglobin content of reticulocytes (Ret-He) and red blood cells (RBC-He) in case of suspected iron deficient erythropoiesis (IDE) in the third trimester of pregnancy. Twenty-five subjects with suspected IDE during pregnancy (Hb ≤ 110g/L, Ret-He < 29.6 pg, zinc protoporphyrin > 75 mol/mol hem) participated in the study. After iron supplementation, reticulocyte counts increased from 0.061 ± 0.015 x 1012/L to 0.079 ± 0.026 x 1012/L and Ret-He increased from 23.6 ± 2.8 pg to 28.3 ± 2.6 pg (P ≤ 0.001). RBC-He increased from 26.9 ± 1.9 pg to 27.4 ± 1.8 pg (not significant, NS) and Ret-He/RBC-He ratio increased from 0.97 ± 0.06 towards 1.07 ± 0.05 (P ≤ 0.001). Hb concentrations demonstrated an obvious increase from 105 ± 6 g/L towards 115 ± 5 g/L (P ≤ 0.001) after supplementation. An obvious increase in RBC distribution width was observed from 45.0 ± 3.6 fL towards 52.3 ± 7.0 fL (P ≤ 0.001). We recommend that Ret-He and Ret-He/RBC-He ratio be integrated into the protocols for anemia screening and for monitoring effects of iron supplementation during pregnancy. In particular, the parameters should be considered in subjects with Hb results in the controversial range of 101–108 g/L.
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