{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T02:39:32Z","timestamp":1791859172156,"version":"4.3.4"},"reference-count":62,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,5,29]],"date-time":"2024-05-29T00:00:00Z","timestamp":1716940800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background\u2014This review provides a comprehensive overview of rare anemias, emphasizing their hereditary and acquired causes, diagnostic advancements, and evolving treatment strategies. It outlines the significance of rare anemias within public health, historical challenges in recognition and treatment, and the role of European initiatives like ENERCA and EuroBloodNet in advancing care. Content\u2014This document discusses diagnostic technologies like next-generation sequencing and the impact of artificial intelligence, alongside the promising avenues of gene therapy, targeted drug treatments, and stem cell transplantation. It underscores the importance of a patient-tailored approach, advances in diagnostic tools, and the necessity for continued research, patient advocacy, and international collaboration to improve outcomes for individuals with rare anemias.<\/jats:p>","DOI":"10.3390\/jcm13113180","type":"journal-article","created":{"date-parts":[[2024,5,29]],"date-time":"2024-05-29T06:58:07Z","timestamp":1716965887000},"page":"3180","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Understanding Rare Anemias: Emerging Frontiers for Diagnosis and Treatment"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1820-2594","authenticated-orcid":false,"given":"Joan-Lluis","family":"Vives Corrons","sequence":"first","affiliation":[{"name":"Rare Anaemias and Erythropoietic Disorders Research, Institute for Leukaemia Research Josep Carreras, 08916 Barcelona, Spain"},{"name":"Ektacytometry Unit, Clinical Centre for Ambulatory Medicine, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,29]]},"reference":[{"key":"ref_1","unstructured":"Wu, Z.H. (2019). Rare Diseases, IntechOpen."},{"key":"ref_2","first-page":"12","article-title":"Enerca: The European network for patients with rare Anaemias","volume":"1","year":"2015","journal-title":"J. Rare Disord. Diagn. Ther."},{"key":"ref_3","first-page":"47","article-title":"EuroBloodNet: From rare anaemias to rare haematological diseases, a transitional proposal for European ref-erence network (ERN)","volume":"2","year":"2016","journal-title":"J. Rare Disord. Diagn. Ther."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"4878","DOI":"10.4081\/thal.2014.4878","article-title":"Recommendations for centres of expertise in rare anaemias. The ENERCA White Book","volume":"4","author":"Gulbis","year":"2014","journal-title":"Thalass. Rep."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1182\/hematology.2021000244","article-title":"The clinical and laboratory evaluation of patients with suspected hypocellular marrow failure","volume":"2021","author":"Keel","year":"2021","journal-title":"Hematol. Am. Soc. Hematol. Educ. Program"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"a463","DOI":"10.3989\/arbor.2018.789n3005","article-title":"Rare Anemias and Hereditary Bone Marrow Failure","volume":"194","author":"VivesCorrons","year":"2018","journal-title":"Arbor"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"101094","DOI":"10.1016\/j.blre.2023.101094","article-title":"Beyond current treatment of Fanconi Anemia: What do advances in cell and gene-based approaches offer?","volume":"60","author":"Guervilly","year":"2023","journal-title":"Blood Rev."},{"key":"ref_8","first-page":"1","article-title":"Perspectives of current understanding and therapeutics of Diamond-Blackfan anemia","volume":"38","author":"Liu","year":"2023","journal-title":"Leukemia"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1274","DOI":"10.1182\/blood.2019000948","article-title":"Congenital dyserythropoietic anemias","volume":"136","author":"Iolascon","year":"2020","journal-title":"Blood"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1182\/blood-2018-08-815951","article-title":"The molecular genetics of sideroblastic anemia","volume":"133","author":"Ducamp","year":"2019","journal-title":"Blood"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1643","DOI":"10.1056\/NEJMra1413485","article-title":"Aplastic Anemia","volume":"379","author":"Young","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_12","unstructured":"Hoffman, R., Benz, E.J., Silberstein, L.E., Heslop, H.E., Weitz, J.I., Salama, M.E., and Abutalib, S.A. (2013). Hematology: Basic Principles and Practice, Elsevier. [8th ed.]."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1007\/BF02982015","article-title":"Relationship Between Aplastic Anemia and Paroxysmal Nocturnal Hemoglobinuria","volume":"75","author":"Kinoshita","year":"2002","journal-title":"Int. J. Hematol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"830172","DOI":"10.3389\/fimmu.2021.830172","article-title":"Insights Into the Emergence of Paroxysmal Nocturnal Hemoglobinuria","volume":"12","author":"Colden","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2182","DOI":"10.1038\/s41375-021-01265-7","article-title":"Current challenges and unmet medical needs in myelodysplastic syndromes","volume":"35","author":"Platzbecker","year":"2021","journal-title":"Leukemia"},{"key":"ref_16","unstructured":"Kliegman, R.M., Stanton, B.F., St. Geme, J., and Schor, N.F. (2024). Nelson Pediatric Textbook of Rare Diseases, Elsevier. [1st ed.]."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1001\/jama.2022.10233","article-title":"Sickle Cell Disease","volume":"328","author":"Kavanagh","year":"2022","journal-title":"J. Am. Med Assoc."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1186\/1750-1172-9-97","article-title":"Haemoglobinopathies in Europe: Health & migration policy perspectives","volume":"9","author":"Martinez","year":"2014","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_19","unstructured":"(2023, December 04). Shining a Light on Thalassemia: Global Report Unveils Knowledge Gaps and Opportunities. Available online: https:\/\/www.news-medical.net\/news\/20231204\/Shining-a-light-on-thalassemia-Global-report-unveils-knowledge-gaps-and-opportunities.aspx."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"656","DOI":"10.3389\/fphys.2018.00656","article-title":"Squeezing for Life\u2014Properties of Red Blood Cell Deformability","volume":"9","author":"Huisjes","year":"2018","journal-title":"Front. Physiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1182\/hematology.2021000266","article-title":"Diagnosis and clinical management of enzymopathies","volume":"2021","author":"Luzzatto","year":"2021","journal-title":"Hematol. Am. Soc. Hematol. Educ. Program"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"461","DOI":"10.2147\/JBM.S353907","article-title":"Pyruvate Kinase Deficiency: Current Challenges and Future Prospects","volume":"13","author":"Fattizzo","year":"2022","journal-title":"J. Blood Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1182\/hematology.2022000405","article-title":"Warm autoimmune hemolytic anemia and the best treatment strategies","volume":"2022","author":"Kuter","year":"2022","journal-title":"Hematol. Am. Soc. Hematol. Educ. Program"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"E153","DOI":"10.1503\/cmaj.160142","article-title":"Thrombotic microangiopathies: A general approach to diagnosis and management","volume":"189","author":"Arnold","year":"2016","journal-title":"Can. Med. Assoc. J."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2181","DOI":"10.1093\/hmg\/10.20.2181","article-title":"Recent advances in disorders of iron metabolism: Mutations, mechanisms and modifiers","volume":"10","author":"Roy","year":"2001","journal-title":"Hum. Mol. Genet."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1097\/MOP.0b013e3283425591","article-title":"Inherited disorders of iron metabolism","volume":"23","author":"Camaschella","year":"2011","journal-title":"Curr. Opin. Pediatr."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"294","DOI":"10.9734\/jpri\/2021\/v33i63A35633","article-title":"Automated Blood Analysers and Their Testing Principles: A Comparative Study","volume":"33","author":"Ragav","year":"2021","journal-title":"J. Pharm. Res. Int."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1843","DOI":"10.1039\/D0LC01235A","article-title":"Emerging point-of-care technologies for anemia detection","volume":"21","author":"An","year":"2021","journal-title":"Lab Chip"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1080\/17474086.2021.1886919","article-title":"Screening tools for hereditary hemolytic anemia: New concepts and strategies","volume":"14","author":"Fermo","year":"2021","journal-title":"Expert Rev. Hematol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"636","DOI":"10.3389\/fphys.2020.00636","article-title":"Clinical Diagnosis of Red Cell Membrane Disorders: Comparison of Osmotic Gradient Ektacytometry and Eosin Maleimide (EMA) Fluorescence Test for Red Cell Band 3 (AE1, SLC4A1) Content for Clinical Diagnosis","volume":"11","author":"Zaidi","year":"2020","journal-title":"Front. Physiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1007\/s12185-020-03010-9","article-title":"Characterization of hereditary red blood cell membranopathies using combined targeted next-generation sequencing and osmotic gradient ektacytometry","volume":"113","author":"Krishnevskaya","year":"2021","journal-title":"Int. J. Hematol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"D\u2019alessandro, A., Krisnevskaya, E., Leguizamon, V., Hern\u00e1ndez, I., de la Torre, C., Bech, J.-J., Navarro, J.-T., and Vives-Corrons, J.-L. (2024). SARS-CoV-2 Infection and Anemia\u2014A Focus on RBC Deformability and Membrane Proteomics\u2014Integrated Observational Prospective Study. Microorganisms, 12.","DOI":"10.3390\/microorganisms12030453"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"755664","DOI":"10.3389\/fphys.2021.755664","article-title":"Editorial: New Methods for Red Blood Cell Research and Diagnosis","volume":"12","author":"Bianchi","year":"2021","journal-title":"Front. Physiol."},{"key":"ref_34","unstructured":"Lesley, A., Clementson, R.S., and Eriksen, A.W. (2022). Advances in Phytoplankton Ecology, Elsevier."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Choi, Y.J., Kim, H., Ahn, W.K., Lee, S.-T., Han, J.W., Choi, J.R., Lyu, C.J., Hahn, S., and Shin, S. (2023). Diagnostic yield of targeted next-generation sequencing for pediatric hereditary hemolytic anemia. BMC Med. Genom., 16.","DOI":"10.1186\/s12920-023-01648-y"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e739","DOI":"10.1097\/HS9.0000000000000739","article-title":"The Use of Next-generation Sequencing in the Diagnosis of Rare Inherited Anaemias: A Joint BSH\/EHA Good Practice Paper","volume":"6","author":"Roy","year":"2022","journal-title":"HemaSphere"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"9907","DOI":"10.1038\/s41598-022-14038-8","article-title":"Analysis of rare thalassemia genetic variants based on third-generation sequencing","volume":"12","author":"Peng","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Munkongdee, T., Chen, P., Winichagoon, P., Fucharoen, S., and Paiboonsukwong, K. (2020). Update in Laboratory Diagnosis of Thalassemia. Front. Mol. Biosci., 7.","DOI":"10.3389\/fmolb.2020.00074"},{"key":"ref_39","first-page":"e46860","article-title":"The Impact of Artificial Intelligence on Optimizing Diagnosis and Treatment Plans for Rare Genetic Disorders","volume":"15","author":"Abdallah","year":"2023","journal-title":"Cureus"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.1038\/s41431-021-00928-4","article-title":"Establishing a second-generation artificial intelligence-based system for improving diagnosis, treatment, and monitoring of patients with rare diseases","volume":"29","author":"Hurvitz","year":"2021","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_41","unstructured":"Rare Insights (2020, October 15). Ensuring Access to Telehealth for Rare Diseases. Available online: https:\/\/rarediseases.org\/wp-content\/uploads\/2020\/10\/NRD-2098-RareInsights-Telehealth-Report-1.pdf."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e576","DOI":"10.1097\/HS9.0000000000000576","article-title":"Innovative Treatments for Rare Anemias","volume":"5","author":"Cappellini","year":"2021","journal-title":"HemaSphere"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"8S24","DOI":"10.1016\/S0929-693X(23)00224-5","article-title":"Recent advances in hematopoietic gene therapy for genetic disorders","volume":"30","author":"Galy","year":"2023","journal-title":"Arch. Pediatr."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1111\/nyas.15070","article-title":"Gene addition for beta thalassemia","volume":"1530","author":"Kwiatkowski","year":"2023","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_45","unstructured":"Sobti, R.C. (2022). Advances in Animal Experimentation and Modeling, Academic Press."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e479","DOI":"10.1097\/HS9.0000000000000479","article-title":"Gene Therapy of the Hemoglobinopathies","volume":"4","author":"Kunz","year":"2020","journal-title":"HemaSphere"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2281","DOI":"10.1038\/nprot.2013.143","article-title":"Genome engineering using the CRISPR-Cas9 system","volume":"8","author":"Hsu","year":"2013","journal-title":"Nat. Protoc."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"4195","DOI":"10.1007\/s00431-023-05093-y","article-title":"Optimizing diagnostic methods and stem cell transplantation outcomes in pediatric bone marrow failure: A 50-year single center experience","volume":"182","author":"Vissers","year":"2023","journal-title":"Eur. J. Pediatr."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"20406207211066070","DOI":"10.1177\/20406207211066070","article-title":"Mitapivat, a novel pyruvate kinase activator, for the treatment of hereditary hemolytic anemias","volume":"12","year":"2021","journal-title":"Ther. Adv. Hematol."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Longo, F., Motta, I., Pinto, V., Piolatto, A., Ricchi, P., Tartaglione, I., and Origa, R. (2023). Treating Thalassemia Patients with Luspatercept: An Expert Opinion Based on Current Evidence. J. Clin. Med., 12.","DOI":"10.3390\/jcm12072584"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1097426","DOI":"10.3389\/fmed.2022.1097426","article-title":"Rise of the planet of rare anemias: An update on emerging treatment strategies","volume":"9","author":"Fattizzo","year":"2023","journal-title":"Front. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"212502","DOI":"10.7573\/dic.212502","article-title":"Advances in iron chelation therapy: Transitioning to a new oral formulation","volume":"6","author":"Shah","year":"2017","journal-title":"Drugs Context"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1016\/S0268-960X(09)70003-7","article-title":"Optimizing iron chelation strategies in \u03b2-thalassaemia major","volume":"23","author":"Porter","year":"2009","journal-title":"Blood Rev."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1111\/ejh.13935","article-title":"Iron chelation therapy","volume":"110","author":"Bruzzese","year":"2023","journal-title":"Eur. J. Haematol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1038\/s41409-023-02133-x","article-title":"Hematopoietic stem cell transplantation in patients with Fanconi anemia: A report of late effects and psychosocial adjustment in life","volume":"59","author":"Ayas","year":"2024","journal-title":"Bone Marrow Transplant."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1038\/s41409-023-02121-1","article-title":"Predictors of outcomes in hematopoietic cell transplantation for Fanconi anemia","volume":"59","author":"Cancio","year":"2024","journal-title":"Bone Marrow Transplant."},{"key":"ref_57","unstructured":"Stepheson, R., Leftkopoulos, S., Mukhopadhyay, M., Faial, T., Floriddia, E., Forte, E., Staal, J., Bardot, E., Luckgen, A., and Breuer, M. (2023, June 13). Innovations in Stem Cell Biology 2023. Nature Collection. Available online: https:\/\/www.nature.com\/collections\/iebebaciag."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"6451","DOI":"10.1182\/bloodadvances.2023010587","article-title":"Treatment strategy for acquired pure red cell aplasia: A systematic review and meta-analysis","volume":"7","author":"Lobbes","year":"2023","journal-title":"Blood Adv."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2040620721998126","DOI":"10.1177\/2040620721998126","article-title":"Current evidence and the emerging role of eltrombopag in severe aplastic anemia","volume":"12","author":"Drexler","year":"2021","journal-title":"Ther. Adv. Hematol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1180509","DOI":"10.3389\/fimmu.2023.1180509","article-title":"The choice of new treatments in autoimmune hemolytic anemia: How to pick from the basket?","volume":"14","author":"Berentsen","year":"2023","journal-title":"Front. Immunol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1111\/imr.13137","article-title":"The complement alternative pathway in paroxysmal nocturnal hemoglobinuria: From a pathogenic mechanism to a therapeutic target","volume":"313","author":"Risitano","year":"2022","journal-title":"Immunol. Rev."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"e17488","DOI":"10.1016\/j.heliyon.2023.e17488","article-title":"Advances in drug delivery systems, challenges and future directions","volume":"9","author":"Ezike","year":"2023","journal-title":"Heliyon"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/11\/3180\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:49:58Z","timestamp":1760107798000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/11\/3180"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,29]]},"references-count":62,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2024,6]]}},"alternative-id":["jcm13113180"],"URL":"https:\/\/doi.org\/10.3390\/jcm13113180","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,29]]}}}