{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T12:27:19Z","timestamp":1784204839054,"version":"3.55.0"},"reference-count":30,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T00:00:00Z","timestamp":1773964800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>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 &gt; 65 years, were recruited in the context of routine health controls. Group differences were assessed using analysis of variance (ANOVA), with p values &lt; 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 &gt; 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\u20130.767), with the best Youden index at a cut-off of 100 \u00b5g\/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\u20130.957); RHe AUC 0.860, 95% CI 0.777\u20130.947; 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\u20130.814). 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.<\/jats:p>","DOI":"10.3390\/diagnostics16060928","type":"journal-article","created":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T08:49:28Z","timestamp":1774255768000},"page":"928","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The\u00a0Role\u00a0of Reticulocyte-Derived Parameters in the Detection of Iron-Restricted Erythropoiesis in the Elderly"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9610-7392","authenticated-orcid":false,"given":"Elo\u00edsa","family":"Urrechaga","sequence":"first","affiliation":[{"name":"Laboratory, Hospital Galdakao Usansolo, 48960 Galdakao, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3685-6930","authenticated-orcid":false,"given":"M\u00f3nica","family":"Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Hematology, Hospital Galdakao Usansolo, 48960 Galdakao, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1002\/ajh.23598","article-title":"Evaluation and management of anemia in the elderly","volume":"89","author":"Goodnough","year":"2014","journal-title":"Am. J. Hematol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1182\/blood-2017-07-746446","article-title":"Anemia at older age: Etiologies, clinical implications, and management","volume":"131","author":"Stauder","year":"2018","journal-title":"Blood"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1182\/blood.2022017626","article-title":"How I treat anemia in older adults","volume":"143","author":"Oyedeji","year":"2024","journal-title":"Blood"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Foug\u00e8re, B., Puisieux, F., Chevalet, P., Annweiler, C., Michel, E., Joly, L., Blanc, F., Azouzi, A.E., Desr\u00e9-Follet, V., and Cacoub, P. (2024). Prevalence of iron deficiency in patients admitted to a geriatric unit: A multicenter cross-sectional study. BMC Geriatr., 24.","DOI":"10.1186\/s12877-024-04719-6"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"4617","DOI":"10.3748\/wjg.15.4617","article-title":"An update on iron physiology","volume":"15","author":"Villar","year":"2009","journal-title":"World J. Gastroenterol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"101337","DOI":"10.1016\/j.blre.2025.101337","article-title":"Old tests and new paradigms: How to interpret iron studies and related biomarkers for the diagnosis of iron deficiency in adults","volume":"74","author":"Kriel","year":"2025","journal-title":"Blood Rev."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Cacoub, P., Choukroun, G., Cohen-Solal, A., Luporsi, E., Peyrin-Biroulet, L., Peoc\u2019h, K., Andrieu, V., Lasocki, S., Puy, H., and Trochu, J.N. (2022). Towards a Common Definition for the Diagnosis of Iron Deficiency in Chronic Inflammatory Diseases. Nutrients, 14.","DOI":"10.3390\/nu14051039"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.cll.2014.10.004","article-title":"Clinical Utility of Reticulocyte Parameters","volume":"35","author":"Piva","year":"2015","journal-title":"Clin. Lab. Med."},{"key":"ref_9","first-page":"154","article-title":"Reticulocyte haemoglobin as a routine parameter in preoperative iron deficiency assessment","volume":"5","author":"Hoenemann","year":"2021","journal-title":"Endocrinol. Metab."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1093\/ajcp\/aqac103","article-title":"Implementing Reticulocyte Hemoglobin into Current Hematology Algorithms","volume":"158","author":"Lundgren","year":"2022","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_11","first-page":"16","article-title":"Reticulocyte hemoglobin in the evaluation of erythropoietic activity and iron availability","volume":"23","author":"Urrechaga","year":"2025","journal-title":"Blood Transfus."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"32","DOI":"10.21037\/jlpm-24-28","article-title":"Reticulocyte Hb expression reported by the Mindray BC6800 Plus analyzer for the detection of iron deficiency in patient blood management","volume":"9","author":"Urrechaga","year":"2024","journal-title":"J. Lab. Precis. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"hvaf086.164","DOI":"10.1093\/clinchem\/hvaf086.164","article-title":"Mean reticulocyte volume reported by Mindray 6800 Plus for the diagnosis of iron restricted erythropoiesis","volume":"71","author":"Urrechaga","year":"2025","journal-title":"Clin. Chem."},{"key":"ref_14","unstructured":"Instituto Nacional de Estad\u00edstica (2025, December 31). Available online: www.ine.es."},{"key":"ref_15","unstructured":"(2026, January 19). Euskalit. Available online: www.euskalit.net."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Busti, F., Campostrini, N., Martinelli, N., and Girelli, D. (2014). Iron deficiency in the elderly population, revisited in the hepcidin era. Front. Pharmacol., 5.","DOI":"10.3389\/fphar.2014.00083"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/j.bpa.2023.11.001","article-title":"Diagnosing iron deficiency: Controversies and novel metrics","volume":"37","author":"Rusch","year":"2023","journal-title":"Best Pract. Res. Clin. Anaesthesiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.eurger.2012.06.005","article-title":"Increased ferritin levels could reflect ongoing aging-associated inflammation and may obscure underlying iron deficiency in the geriatric population","volume":"3","author":"Cankurtaran","year":"2012","journal-title":"Eur. Geriatr. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1007\/s12603-019-1214-x","article-title":"Anemia of Old Age","volume":"23","author":"Sanford","year":"2019","journal-title":"J. Nutr. Health Aging"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"mfab030","DOI":"10.1093\/mtomcs\/mfab030","article-title":"Optimal serum ferritin level range: Iron status measure and inflammatory biomarker","volume":"13","author":"DePalma","year":"2021","journal-title":"Metallomics"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1111\/ijlh.14016","article-title":"Defining ferritin clinical decision limits to improve diagnosis and treatment of iron deficiency: A modified Delphi study","volume":"45","author":"Naveed","year":"2023","journal-title":"Int. J. Lab. Hematol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Cancado, R.D., Leite, L.A.C., and Mu\u00f1oz, M. (2025). Defining Global Thresholds for Serum Ferritin: A Challenging Mission in Establishing the Iron Deficiency Diagnosis in This Era of Striving for Health Equity. Diagnostics, 15.","DOI":"10.3390\/diagnostics15030289"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1001\/archinte.162.4.445","article-title":"Diagnosis of Iron Deficiency Anemia in the Elderly by Transferrin Receptor\u2013Ferritin Index","volume":"162","author":"Rimon","year":"2002","journal-title":"Arch. Intern. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.3324\/haematol.2014.109967","article-title":"Anemia in the elderly: Clinical implications and new therapeutic concepts","volume":"99","author":"Stauder","year":"2014","journal-title":"Haematologica"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"201","DOI":"10.3390\/hematolrep15010021","article-title":"Reticulocyte Hemoglobin as a Screening Test for Iron Deficiency Anemia: A New Cut-Off","volume":"15","author":"Aedh","year":"2023","journal-title":"Hematol. Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"925907","DOI":"10.1155\/2011\/925907","article-title":"Comparative evaluation of the reticulocyte hemoglobin content assay when screening for iron deficiency in elderly anemic patients","volume":"2011","author":"Karlsson","year":"2011","journal-title":"Anemia"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.ejim.2012.09.001","article-title":"Is analysis of the reticulocyte haemoglobin equivalent a useful test for the diagnosis of iron deficiency anaemia in geriatric patients?","volume":"24","author":"Joosten","year":"2013","journal-title":"Eur. J. Intern. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4103\/joah.joah_103_23","article-title":"Reticulocyte hemoglobin content: Advancing the frontiers in iron deficiency anemia diagnosis and management","volume":"15","author":"Almashjary","year":"2024","journal-title":"J. Appl. Hematol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1515\/cclm-2025-1032","article-title":"Automated reticulocyte counting: Advances, standardization challenges, and clinical accessibility","volume":"64","author":"Zhou","year":"2026","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1111\/ijlh.14209","article-title":"Report of the International Council for Standardization in Haematology working group for standardization of reticulocyte parameters","volume":"46","author":"Obstfeld","year":"2024","journal-title":"Int. J. Lab. Hematol."}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/16\/6\/928\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T08:55:58Z","timestamp":1774256158000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/16\/6\/928"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,20]]},"references-count":30,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["diagnostics16060928"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics16060928","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,20]]}}}