{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T11:20:09Z","timestamp":1792495209748,"version":"4.5.0"},"reference-count":56,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,4,26]],"date-time":"2023-04-26T00:00:00Z","timestamp":1682467200000},"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>Thalassemia is an autosomal recessive genetic disorder that affects the beta or alpha subunits of the hemoglobin structure. Thalassemia is classified as a hypochromic microcytic anemia and a definitive diagnosis of thalassemia is made by genetic testing of the alpha and beta genes. Thalassemia carries similar features to the other diseases that lead to microcytic hypochromic anemia, particularly iron deficiency anemia (IDA). Therefore, distinguishing between thalassemia and other causes of microcytic anemia is important to help in the treatment of the patients. Different indices and algorithms are used based on the complete blood count (CBC) parameters to diagnose thalassemia. In this article, we review how effective artificial intelligence is in aiding in the diagnosis and classification of thalassemia.<\/jats:p>","DOI":"10.3390\/diagnostics13091551","type":"journal-article","created":{"date-parts":[[2023,4,26]],"date-time":"2023-04-26T04:42:54Z","timestamp":1682484174000},"page":"1551","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Applications of Artificial Intelligence in Thalassemia: A Comprehensive Review"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0562-8123","authenticated-orcid":false,"given":"Khaled","family":"Ferih","sequence":"first","affiliation":[{"name":"College of Medicine, QU Health, Qatar University, Doha P.O. Box 2713, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5983-0135","authenticated-orcid":false,"given":"Basel","family":"Elsayed","sequence":"additional","affiliation":[{"name":"College of Medicine, QU Health, Qatar University, Doha P.O. Box 2713, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2266-7784","authenticated-orcid":false,"given":"Amgad M.","family":"Elshoeibi","sequence":"additional","affiliation":[{"name":"College of Medicine, QU Health, Qatar University, Doha P.O. Box 2713, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4927-9888","authenticated-orcid":false,"given":"Ahmed A.","family":"Elsabagh","sequence":"additional","affiliation":[{"name":"College of Medicine, QU Health, Qatar University, Doha P.O. Box 2713, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3075-9600","authenticated-orcid":false,"given":"Mohamed","family":"Elhadary","sequence":"additional","affiliation":[{"name":"College of Medicine, QU Health, Qatar University, Doha P.O. Box 2713, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashraf","family":"Soliman","sequence":"additional","affiliation":[{"name":"Hematology Section, Pediatrics Department, Hamad Medical Corporation (HMC), Doha P.O. Box 3050, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed","family":"Abdalgayoom","sequence":"additional","affiliation":[{"name":"Hematology Section, Medical Oncology, National Center for Cancer Care and Research (NCCCR), Hamad Medical Corporation (HMC), Doha P.O. Box 3050, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Yassin","sequence":"additional","affiliation":[{"name":"College of Medicine, QU Health, Qatar University, Doha P.O. Box 2713, Qatar"},{"name":"Hematology Section, Medical Oncology, National Center for Cancer Care and Research (NCCCR), Hamad Medical Corporation (HMC), Doha P.O. Box 3050, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"74","DOI":"10.3389\/fmolb.2020.00074","article-title":"Update in Laboratory Diagnosis of Thalassemia","volume":"7","author":"Munkongdee","year":"2020","journal-title":"Front. Mol. Biosci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e2017018","DOI":"10.4084\/mjhid.2017.018","article-title":"\u03b2-Thalassemia Distribution in the Old World: An Ancient Disease Seen from a Historical Standpoint","volume":"9","author":"Kattamis","year":"2017","journal-title":"Mediterr. J. Hematol. Infect. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1111\/j.1749-6632.1998.tb10482.x","article-title":"Global epidemiology of hemoglobin disorders","volume":"850","author":"Angastiniotis","year":"1998","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1056\/NEJMra050436","article-title":"\u03b2-Thalassemia","volume":"353","author":"Rund","year":"2005","journal-title":"N. Engl. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1182\/blood-2013-06-508325","article-title":"A systematic analysis of global anemia burden from 1990 to 2010","volume":"123","author":"Kassebaum","year":"2014","journal-title":"Blood"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1056\/NEJMoa2031054","article-title":"CRISPR-Cas9 Gene Editing for Sickle Cell Disease and \u03b2-Thalassemia","volume":"384","author":"Frangoul","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2826","DOI":"10.1111\/trf.14875","article-title":"Transfusion practices and complications in thalassemia","volume":"58","author":"Lal","year":"2018","journal-title":"Transfusion"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.hoc.2017.11.006","article-title":"Clinical Classification, Screening and Diagnosis for Thalassemia","volume":"32","author":"Viprakasit","year":"2018","journal-title":"Hematol. Oncol. Clin. N. Am."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"103886","DOI":"10.1016\/j.chemolab.2019.103886","article-title":"Determination of the effect of red blood cell parameters in the discrimination of iron deficiency anemia and beta thalassemia via Neighborhood Component Analysis Feature Selection-Based machine learning","volume":"196","author":"Tuncer","year":"2020","journal-title":"Chemom. Intell. Lab. Syst."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1080\/17474086.2021.1860003","article-title":"The spectrum of beta-thalassemia mutations in the 22 Arab countries: A systematic review","volume":"14","author":"Khan","year":"2021","journal-title":"Expert Rev. Hematol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1016\/S0140-6736(73)91446-3","article-title":"Differentiation of iron deficiency from thalassaemia trait","volume":"1","author":"Mentzer","year":"1973","journal-title":"Lancet"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1111\/ijlh.12527","article-title":"Laboratory diagnosis of thalassemia","volume":"38","author":"Brancaleoni","year":"2016","journal-title":"Int. J. Lab. Hematol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1093\/ajcp\/85.4.445","article-title":"Limitations of red blood cell distribution width (RDW) in evaluation of microcytosis","volume":"85","author":"Flynn","year":"1986","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/S0140-6736(73)91878-3","article-title":"Differentiation of iron deficiency from thalassaemia trait by routine blood-count","volume":"301","author":"England","year":"1973","journal-title":"Lancet"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e2019026","DOI":"10.4084\/mjhid.2019.026","article-title":"Final Height and Endocrine Complications in Patients with \u03b2-Thalassemia Intermedia: Our Experience in Non-Transfused Versus Infrequently Transfused Patients and Correlations with Liver Iron Content","volume":"11","author":"Yassin","year":"2019","journal-title":"Mediterr. J. Hematol. Infect. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.bcmd.2009.01.002","article-title":"Improving survival with deferiprone treatment in patients with thalassemia major: A prospective multicenter randomised clinical trial under the auspices of the Italian Society for Thalassemia and Hemoglobinopathies","volume":"42","author":"Maggio","year":"2009","journal-title":"Blood Cells Mol. Dis."},{"key":"ref_17","first-page":"1187","article-title":"Survival of medically treated thalassemia patients in Cyprus. Trends and risk factors over the period 1980\u20132004","volume":"91","author":"Telfer","year":"2006","journal-title":"Haematologica"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1111\/j.1365-2141.2009.07970.x","article-title":"Normalisation of total body iron load with very intensive combined chelation reverses cardiac and endocrine complications of thalassaemia major","volume":"148","author":"Farmaki","year":"2010","journal-title":"Br. J. Haematol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3436","DOI":"10.1182\/blood-2006-02-002394","article-title":"Oral chelators deferasirox and deferiprone for transfusional iron overload in thalassemia major: New data, new questions","volume":"107","author":"Neufeld","year":"2006","journal-title":"Blood"},{"key":"ref_20","first-page":"Cd012349","article-title":"Interventions for improving adherence to iron chelation therapy in people with sickle cell disease or thalassaemia","volume":"5","author":"Fortin","year":"2018","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e2018064","DOI":"10.4084\/mjhid.2018.064","article-title":"Jadenu(\u00ae) Substituting Exjade(\u00ae) in Iron Overloaded \u03b2-Thalassemia Major (BTM) Patients: A Preliminary Report of the Effects on the Tolerability, Serum Ferritin Level, Liver Iron Concentration and Biochemical Profiles","volume":"10","author":"Yassin","year":"2018","journal-title":"Mediterr. J. Hematol. Infect. Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1016\/j.fertnstert.2012.05.047","article-title":"Acute effects of blood transfusion on pituitary gonadal axis and sperm parameters in adolescents and young men with thalassemia major: A pilot study","volume":"98","author":"Soliman","year":"2012","journal-title":"Fertil. Steril."},{"key":"ref_23","first-page":"278","article-title":"Age related IGF-I changes and IGF-I generation in thalassemia major","volume":"8","author":"Soliman","year":"2011","journal-title":"Pediatr. Endocrinol. Rev."},{"key":"ref_24","first-page":"33","article-title":"Statural Growth and Prevalence of Endocrinopathies in Relation to Liver Iron Content (LIC) in Adult Patients with Beta Thalassemia Major (BTM) and Sickle Cell Disease (SCD)","volume":"89","author":"Soliman","year":"2018","journal-title":"Acta Biomed. Atenei Parm."},{"key":"ref_25","first-page":"e2014074","article-title":"Insulin-like Growth Factor-1 (IGF-1): Demographic, Clinical and Laboratory Data in 120 Consecutive Adult Patients with Thalassaemia Major","volume":"6","author":"Soliman","year":"2014","journal-title":"Mediterr. J. Hematol. Infect. Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"546","DOI":"10.4103\/2230-8210.137516","article-title":"Effects of the anti-receptor activator of nuclear factor kappa B ligand denusomab on beta thalassemia major-induced osteoporosis","volume":"18","author":"Yassin","year":"2014","journal-title":"Indian J. Endocrinol. Metab."},{"key":"ref_27","unstructured":"De Sanctis, V., Soliman, A., Candini, G., Campisi, S., Anastasi, S., and Iassin, M. (2013). High prevalence of central hypothyroidism in adult patients with \u03b2-thalassemia major. Georgian Med. News, 88\u201394."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"490","DOI":"10.4103\/2230-8210.111647","article-title":"Detection of glycemic abnormalities in adolescents with beta thalassemia using continuous glucose monitoring and oral glucose tolerance in adolescents and young adults with \u03b2-thalassemia major: Pilot study","volume":"17","author":"Soliman","year":"2013","journal-title":"Indian J. Endocrinol. Metab."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.lfs.2018.08.067","article-title":"Oxidative stress\u2013chronic kidney disease\u2013cardiovascular disease: A vicious circle","volume":"210","author":"Ravarotto","year":"2018","journal-title":"Life Sci."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Ravarotto, V., Bertoldi, G., Innico, G., Gobbi, L., and Cal\u00f2, L.A. (2021). The Pivotal Role of Oxidative Stress in the Pathophysiology of Cardiovascular-Renal Remodeling in Kidney Disease. Antioxidants, 10.","DOI":"10.3390\/antiox10071041"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Nalesso, F., Rigato, M., Cirella, I., Protti, M.P., Zanella, R., Rossi, B., Putti, M.C., Martino, F.K., and Cal\u00f2, L.A. (2022). The Assessment of Renal Functional Reserve in \u03b2-Thalassemia Major Patients by an Innovative Ultrasound and Doppler Technique: A Pilot Study. J. Clin. Med., 11.","DOI":"10.3390\/jcm11226752"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1111\/j.1751-553X.2007.00966.x","article-title":"Evaluation of the diagnostic reliability of different RBC indices and formulas in the differentiation of the \u03b2-thalassaemia minor from iron deficiency in Palestinian population","volume":"30","author":"Sirdah","year":"2008","journal-title":"Int. J. Lab. Hematol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1097\/00043426-199907000-00040","article-title":"#262 Differentiating iron deficiency anemia from thalassemia minor by using an RDW-based index","volume":"21","author":"Jayabose","year":"1999","journal-title":"J. Pediatr. Hematol. Oncol."},{"key":"ref_34","unstructured":"Huber, A., Ottiger, C., Risch, L., Regenass, S., Hergersberg, M., and Herklotz, R. (2004). Swiss Medical Forum, EMH Medi."},{"key":"ref_35","first-page":"481","article-title":"A new red cell discriminant incorporating volume dispersion for differentiating iron deficiency anemia from thalassemia minor","volume":"15","author":"Green","year":"1989","journal-title":"Blood Cells"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"473","DOI":"10.3923\/pjbs.2009.473.475","article-title":"A new index for discrimination between iron deficiency anemia and beta-thalassemia minor: Results in 284 patients","volume":"12","author":"Ehsani","year":"2009","journal-title":"Pak. J. Biol. Sci. PJBS"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1832","DOI":"10.1056\/NEJMra1401038","article-title":"Iron-Deficiency Anemia","volume":"372","author":"Camaschella","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_38","first-page":"671","article-title":"Iron deficiency anemia","volume":"75","author":"Killip","year":"2007","journal-title":"Am. Fam. Physician"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.artmed.2018.04.009","article-title":"Identifying \u03b2-thalassemia carriers using a data mining approach: The case of the Gaza Strip, Palestine","volume":"88","author":"AlAgha","year":"2018","journal-title":"Artif. Intell. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.bjhh.2016.05.011","article-title":"A new index to discriminate between iron deficiency anemia and thalassemia trait","volume":"38","author":"Matos","year":"2016","journal-title":"Rev. Bras. Hematol. Hemoter."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"78","DOI":"10.5455\/aim.2019.27.78-84","article-title":"Differential Diagnosis of Iron-Deficiency Anemia from \u03b2-Thalassemia Trait Using an Intelligent Model in Comparison with Discriminant Indexes","volume":"27","author":"Kabootarizadeh","year":"2019","journal-title":"Acta Inf. Med"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Bellinger, C., Amid, A., Japkowicz, N., and Victor, H. (205, January 9\u201311). Multi-label classification of anemia patients. Proceedings of the 2015 IEEE 14th International Conference on Machine Learning and Applications (ICMLA), Miami, FL, USA.","DOI":"10.1109\/ICMLA.2015.112"},{"key":"ref_43","first-page":"55","article-title":"Discrimination between Iron Deficiency Anaemia (IDA) and \u03b2-Thalassemia Trait (\u03b2-TT) Based on Pattern-Based Input Selection Artificial Neural Network (PBIS- ANN)","volume":"7","author":"Jamei","year":"2016","journal-title":"J. Adv. Comput. Res."},{"key":"ref_44","first-page":"1627","article-title":"Evaluation of five discriminating indexes to distinguish Beta-Thalassemia Trait from Iron Deficiency Anaemia","volume":"66","author":"Ullah","year":"2016","journal-title":"J. Pak. Med. Assoc."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Fu, Y.-K., Liu, H.-M., Lee, L.-H., Chen, Y.-J., Chien, S.-H., Lin, J.-S., Chen, W.-C., Cheng, M.-H., Lin, P.-H., and Lai, J.-Y. (2021). The TVGH-NYCU Thal-Classifier: Development of a Machine-Learning Classifier for Differentiating Thalassemia and Non-Thalassemia Patients. Diagnostics, 11.","DOI":"10.3390\/diagnostics11091725"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/S0169-7439(03)00094-7","article-title":"A comparative study of K-Nearest Neighbour, Support Vector Machine and Multi-Layer Perceptron for Thalassemia screening","volume":"69","author":"Amendolia","year":"2003","journal-title":"Chemom. Intell. Lab. Syst."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1016\/j.ins.2006.07.009","article-title":"Thalassemia classification by neural networks and genetic programming","volume":"177","author":"Wongseree","year":"2007","journal-title":"Inf. Sci."},{"key":"ref_48","first-page":"55","article-title":"Comparison of Different Classification Techniques Using WEKA for Hematological Data","volume":"4","author":"Amin","year":"2015","journal-title":"Am. J. Eng. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"140","DOI":"10.18178\/ijmlc.2018.8.2.677","article-title":"Machine learning in predicting hemoglobin variants","volume":"8","author":"Bhuyan","year":"2018","journal-title":"Int. J. Mach. Learn. Comput."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.jare.2020.04.005","article-title":"A decision support scheme for beta thalassemia and HbE carrier screening","volume":"24","author":"Das","year":"2020","journal-title":"J. Adv. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1016\/S0140-6736(73)90637-5","article-title":"Iron deficiency and-or thalassaemia trait","volume":"1","author":"Srivastava","year":"1973","journal-title":"Lancet"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1016\/S0140-6736(77)92128-6","article-title":"A strategy to detect beta-thalassaemia minor","volume":"1","author":"Shine","year":"1977","journal-title":"Lancet"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"109611","DOI":"10.1016\/j.mehy.2020.109611","article-title":"Discrimination of \u03b2-thalassemia and iron deficiency anemia through extreme learning machine and regularized extreme learning machine based decision support system","volume":"138","author":"Tuncer","year":"2020","journal-title":"Med. Hypotheses"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"4573","DOI":"10.1007\/s11042-019-07927-0","article-title":"Detection of microcytic hypochromia using cbc and blood film features extracted from convolution neural network by different classifiers","volume":"79","author":"Purwar","year":"2020","journal-title":"Multimed. Tools Appl."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1386","DOI":"10.1097\/01.HS9.0000848876.08561.34","article-title":"P1505: Using Artificial Intelligence Neural Networks to Obtain Automated Liver Iron Concentration Measurements Using Magnetic Resonance Imaging\u2014A Multi-Scanner Validation Study","volume":"6","author":"Aydinok","year":"2022","journal-title":"Hemasphere"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1002\/jmri.28300","article-title":"Deep Learning Staging of Liver Iron Content From Multiecho MR Images","volume":"57","author":"Positano","year":"2022","journal-title":"J. Magn. 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