{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T18:35:31Z","timestamp":1789670131109,"version":"4.0.1"},"reference-count":88,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T00:00:00Z","timestamp":1758240000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Chiesi Farmaceutici S.p.A."},{"name":"Bayer"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: This multicenter cross-sectional study aimed to assess the prevalence of vascular, hepatic, cardiac, endocrine, and bone complications and to identify factors associated with their occurrence in adult patients with neo-transfusion-dependent thalassemia (neo-TDT). Methods: A total of 140 adult neo-TDT patients (defined as receiving &gt;4 transfusions\/year; mean age 44.3 \u00b1 12.1 years; 56.4% female) were retrospectively enrolled from the Extension\u2013Myocardial Iron Overload in Thalassemia (E-MIOT) network. Iron overload (IO) was assessed by magnetic resonance imaging and complications were classified according to established clinical criteria. Logistic regression analyses were performed to investigate associations of complications with age, sex, splenectomy status, chelation therapy, hemoglobin &lt; 9 g\/dL, ferritin \u2265 1000 ng\/mL, and hepatic, pancreatic, and cardiac IO. Results: Complications affecting fewer than 5% of patients\u2014including leg ulcers, cirrhosis, thrombosis, heart failure, and hypoparathyroidism\u2014were excluded from statistical analysis. Bone metabolism disorders were the most prevalent complications (68.6%), followed by impaired glucose metabolism (15.7%). The prevalence of other complications was: extramedullary hematopoiesis (EMH) 19.3%, pulmonary hypertension (PH) 7.1%, arrhythmias 12.1%, hypogonadism 11.4%, and hypothyroidism 15.0%. Male sex was independently associated with EMH (odds-ratio [OR] = 2.67; p = 0.027). Hepatic IO was the only significant predictor of PH (OR = 4.12; p = 0.047). Arrhythmias were strongly associated with older age (OR = 22.67; p &lt; 0.0001), while both older age (OR = 4.42; p = 0.004) and pancreatic IO (OR = 7.40; p = 0.012) were independently associated with impaired glucose metabolism. No significant associations were identified for hypogonadism, hypothyroidism, or bone metabolism disorders. Conclusion: This study offers updated insights into the burden of complications in neo-TDT patients and highlights specific risk factors that may inform comprehensive, multidisciplinary surveillance strategies.<\/jats:p>","DOI":"10.3390\/jcm14186602","type":"journal-article","created":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T10:08:58Z","timestamp":1758276538000},"page":"6602","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Determinants of Multi-Organ Morbidity in Neo-Transfusion-Dependent Thalassemia: A Cross-Sectional Analysis"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2284-8585","authenticated-orcid":false,"given":"Antonella","family":"Meloni","sequence":"first","affiliation":[{"name":"Bioengineering Unit, Fondazione G. Monasterio CNR-Regione Toscana, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7361-3308","authenticated-orcid":false,"given":"Paolo","family":"Ricchi","sequence":"additional","affiliation":[{"name":"Unit\u00e0 Operativa Semplice Dipartimentale Malattie Rare del Globulo Rosso, Azienda Ospedaliera di Rilievo Nazionale \u201cA. Cardarelli\u201d, 80131 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5319-2769","authenticated-orcid":false,"given":"Laura","family":"Pistoia","sequence":"additional","affiliation":[{"name":"Unit\u00e0 Operativa Complessa Ricerca Clinica, Fondazione G. Monasterio CNR-Regione Toscana, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0434-0382","authenticated-orcid":false,"given":"Filomena","family":"Longo","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina Specialistica\u2014Day Hospital della Talassemia e delle Emoglobinopatie, Azienda Ospedaliero-Universitaria Arcispedale \u201cS. Anna\u201d, 44124 Cona, FE, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerio","family":"Cecinati","sequence":"additional","affiliation":[{"name":"Struttura Semplice di Microcitemia, Ospedale \u201cSS. Annunziata\u201d, 74123 Taranto, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zelia","family":"Borsellino","sequence":"additional","affiliation":[{"name":"Unit\u00e0 Operativa Complessa Ematologia con Talassemia, ARNAS Civico \u201cBenfratelli-Di Cristina\u201d, 90134 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Sorrentino","sequence":"additional","affiliation":[{"name":"Unit\u00e0 Operativa Semplice Day Hospital Talassemici, Ospedale \u201cSant\u2019Eugenio\u201d, 00143 Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabetta","family":"Corigliano","sequence":"additional","affiliation":[{"name":"Ematologia Microcitemia, Ospedale San Giovanni di Dio\u2014ASP Crotone, 88900 Crotone, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michela","family":"Zerbini","sequence":"additional","affiliation":[{"name":"Diagnostica per Immagini e Radiologia Interventistica, Ospedale del Delta, 44023 Lagosanto, FE, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priscilla","family":"Fina","sequence":"additional","affiliation":[{"name":"Unit\u00e0 Operativa Complessa Diagnostica per Immagini, Ospedale \u201cSandro Pertini\u201d, 00157 Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ada","family":"Riva","sequence":"additional","affiliation":[{"name":"Struttura Complessa di Radiologia, Ospedale \u201cSS. Annunziata\u201d, 74123 Taranto, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-5840-6783","authenticated-orcid":false,"given":"Giuseppe","family":"Peritore","sequence":"additional","affiliation":[{"name":"Unit\u00e0 Operativa Complessa di Radiologia, ARNAS Civico \u201cBenfratelli-Di Cristina\u201d, 90134 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6955-9572","authenticated-orcid":false,"given":"Vincenzo","family":"Positano","sequence":"additional","affiliation":[{"name":"Bioengineering Unit, Fondazione G. Monasterio CNR-Regione Toscana, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4285-9468","authenticated-orcid":false,"given":"Alberto","family":"Clemente","sequence":"additional","affiliation":[{"name":"Department of Radiology, Fondazione G. Monasterio CNR-Regione Toscana, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Weatherall, D.J., and Clegg, J.B. (2001). The Thalassemia Syndromes, Blackwell Science.","DOI":"10.1002\/9780470696705"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"81","DOI":"10.3390\/thalassrep14040010","article-title":"Thalassemia: Pathophysiology, Diagnosis, and Advances in Treatment","volume":"14","author":"Sadiq","year":"2024","journal-title":"Thalass. Rep."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Angastiniotis, M., and Lobitz, S. (2019). Thalassemias: An Overview. Int. J. Neonatal. Screen, 5.","DOI":"10.3390\/ijns5010016"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/S0140-6736(17)31822-6","article-title":"Thalassaemia","volume":"391","author":"Taher","year":"2018","journal-title":"Lancet"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1016\/S0268-960X(12)70003-6","article-title":"The definition and epidemiology of non-transfusion-dependent thalassemia","volume":"26","author":"Weatherall","year":"2012","journal-title":"Blood Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"833","DOI":"10.3324\/haematol.2012.066845","article-title":"Non-transfusion-dependent thalassemias","volume":"98","author":"Musallam","year":"2013","journal-title":"Haematologica"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/vox.12201","article-title":"When to consider transfusion therapy for patients with non-transfusion-dependent thalassaemia","volume":"108","author":"Taher","year":"2015","journal-title":"Vox Sang."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1111\/bjh.16753","article-title":"Longitudinal follow-up of patients with thalassaemia intermedia who started transfusion therapy in adulthood: A cohort study","volume":"191","author":"Ricchi","year":"2020","journal-title":"Br. J. Haematol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e806","DOI":"10.1097\/HS9.0000000000000806","article-title":"Untreated Anemia in Nontransfusion-dependent \u03b2-thalassemia: Time to Sound the Alarm","volume":"6","author":"Musallam","year":"2022","journal-title":"HemaSphere"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"E54","DOI":"10.1002\/ajh.26056","article-title":"Revisiting the non-transfusion-dependent (NTDT) vs. transfusion-dependent (TDT) thalassemia classification 10 years later","volume":"96","author":"Musallam","year":"2021","journal-title":"Am. J. Hematol"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4321","DOI":"10.1182\/blood-2011-03-283614","article-title":"\u03b2-thalassemia: A model for elucidating the dynamic regulation of ineffective erythropoiesis and iron metabolism","volume":"118","author":"Ginzburg","year":"2011","journal-title":"Blood"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e11","DOI":"10.4081\/thal.2013.s1.e11","article-title":"Iron overload in non-transfusion-dependent thalassemia","volume":"3","author":"Musallam","year":"2013","journal-title":"Thal. Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1111\/bjh.14373","article-title":"Iron overload across the spectrum of non-transfusion-dependent thalassaemias: Role of erythropoiesis, splenectomy and transfusions","volume":"176","author":"Porter","year":"2017","journal-title":"Br. J. Haematol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"260","DOI":"10.3324\/haematol.2019.232124","article-title":"Iron metabolism and iron disorders revisited in the hepcidin era","volume":"105","author":"Camaschella","year":"2020","journal-title":"Haematologica"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Meloni, A., Pistoia, L., Gamberini, M.R., Ricchi, P., Cecinati, V., Sorrentino, F., Cuccia, L., Allo, M., Righi, R., and Fina, P. (2021). The Link of Pancreatic Iron with Glucose Metabolism and Cardiac Iron in Thalassemia Intermedia: A Large, Multicenter Observational Study. J. Clin. Med., 10.","DOI":"10.3390\/jcm10235561"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1007\/s11547-024-01821-y","article-title":"Multiparametric cardiac magnetic resonance in patients with thalassemia intermedia: New insights from the E-MIOT network","volume":"129","author":"Meloni","year":"2024","journal-title":"Radiol. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"793025","DOI":"10.1155\/2015\/793025","article-title":"Prevalence and Risk Factors for Complications in Patients with Nontransfusion Dependent Alpha- and Beta-Thalassemia","volume":"2015","author":"Winichakoon","year":"2015","journal-title":"Anemia"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Sleiman, J., Tarhini, A., Bou-Fakhredin, R., Saliba, A.N., Cappellini, M.D., and Taher, A.T. (2018). Non-Transfusion-Dependent Thalassemia: An Update on Complications and Management. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19010182"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Baldini, M., Marcon, A., Cassin, R., Ulivieri, F.M., Spinelli, D., Cappellini, M.D., and Graziadei, G. (2014). Beta-Thalassaemia Intermedia: Evaluation of Endocrine and Bone Complications. BioMed Res. Int., 2014.","DOI":"10.1155\/2014\/174581"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.bcmd.2013.01.015","article-title":"Evaluation of the 5mg\/g liver iron concentration threshold and its association with morbidity in patients with \u03b2-thalassemia intermedia","volume":"51","author":"Musallam","year":"2013","journal-title":"Blood Cells Mol. Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2246","DOI":"10.1007\/s00330-018-5783-6","article-title":"Multicenter validation of the magnetic resonance T2* technique for quantification of pancreatic iron","volume":"29","author":"Meloni","year":"2019","journal-title":"Eur. Radiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1002\/jmri.22417","article-title":"Single region of interest versus multislice T2* MRI approach for the quantification of hepatic iron overload","volume":"33","author":"Meloni","year":"2011","journal-title":"J. Magn. Reson. Imaging"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1002\/mrm.22640","article-title":"Regional and global pancreatic T*(2) MRI for iron overload assessment in a large cohort of healthy subjects: Normal values and correlation with age and gender","volume":"65","author":"Restaino","year":"2011","journal-title":"Magn. Reson. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1016\/j.ijcard.2014.09.139","article-title":"Different patterns of myocardial iron distribution by whole-heart T2* magnetic resonance as risk markers for heart complications in thalassemia major","volume":"177","author":"Meloni","year":"2014","journal-title":"Int. J. Cardiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1460","DOI":"10.1182\/blood-2004-10-3982","article-title":"MRI R2 and R2* mapping accurately estimates hepatic iron concentration in transfusion-dependent thalassemia and sickle cell disease patients","volume":"106","author":"Wood","year":"2005","journal-title":"Blood"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1056\/NEJM200008033430503","article-title":"Hepatic iron concentration and total body iron stores in thalassemia major","volume":"343","author":"Angelucci","year":"2000","journal-title":"N. Engl. J. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3129","DOI":"10.1007\/s00261-015-0522-9","article-title":"Accurate estimate of pancreatic T2* values: How to deal with fat infiltration","volume":"40","author":"Meloni","year":"2015","journal-title":"Abdom. Imaging"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1161\/hc0402.102975","article-title":"Standardized myocardial segmentation and nomenclature for tomographic imaging of the heart: A statement for healthcare professionals from the Cardiac Imaging Committee of the Council on Clinical Cardiology of the American Heart Association","volume":"105","author":"Cerqueira","year":"2002","journal-title":"Circulation"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1186\/s12968-021-00765-w","article-title":"Myocardial iron overload by cardiovascular magnetic resonance native segmental T1 mapping: A sensitive approach that correlates with cardiac complications","volume":"23","author":"Meloni","year":"2021","journal-title":"J. Cardiovasc. Magn. Reson."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"43S","DOI":"10.1002\/hep.510260708","article-title":"Diagnostic tests for hepatitis C","volume":"26","author":"Gretch","year":"1997","journal-title":"Hepatology"},{"key":"ref_31","first-page":"391","article-title":"Oral glucose tolerance testing","volume":"41","author":"Phillips","year":"2012","journal-title":"Aust. Fam. Physician"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1007\/s00259-024-06912-6","article-title":"Updated practice guideline for dual-energy X-ray absorptiometry (DXA)","volume":"52","author":"Slart","year":"2025","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_33","first-page":"1039","article-title":"Diagnosis and treatment of venous leg ulcers: S2k Guideline of the German Society of Phlebology and Lymphology (DGPL) e.V","volume":"22","author":"Valesky","year":"2024","journal-title":"JDDG J. Dtsch. Dermatol. Ges."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"(2018). European Association for the Study of the Liver (EASL) Recommendations on Treatment of Hepatitis C 2018. J. Hepatol., 69, 461\u2013511.","DOI":"10.1016\/j.jhep.2018.03.026"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"515","DOI":"10.2459\/JCM.0b013e3282f20847","article-title":"Guideline recommendations for heart complications in thalassemia major","volume":"9","author":"Cogliandro","year":"2008","journal-title":"J. Cardiovasc. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3599","DOI":"10.1093\/eurheartj\/ehab368","article-title":"2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure","volume":"42","author":"McDonagh","year":"2021","journal-title":"Eur. Heart J."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2534","DOI":"10.1161\/CIRCULATIONAHA.106.180199","article-title":"ACC\/AHA\/HRS 2006 key data elements and definitions for electrophysiological studies and procedures: A report of the American College of Cardiology\/American Heart Association Task Force on Clinical Data Standards (ACC\/AHA\/HRS Writing Committee to Develop Data Standards on Electrophysiology)","volume":"114","author":"Buxton","year":"2006","journal-title":"Circulation"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e2016058","DOI":"10.4084\/mjhid.2016.058","article-title":"The ICET-A Recommendations for the Diagnosis and Management of Disturbances of Glucose Homeostasis in Thalassemia Major Patients","volume":"8","author":"Soliman","year":"2016","journal-title":"Mediterr. J. Hematol. Infect. Dis."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"8","DOI":"10.4103\/2230-8210.107808","article-title":"Growth and endocrine disorders in thalassemia: The international network on endocrine complications in thalassemia (I-CET) position statement and guidelines","volume":"17","author":"Soliman","year":"2013","journal-title":"Indian J. Endocrinol. Metab."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e2019029","DOI":"10.4084\/mjhid.2019.029","article-title":"Thyroid Disorders in Homozygous \u03b2-Thalassemia: Current Knowledge, Emerging Issues and Open Problems","volume":"11","author":"Soliman","year":"2019","journal-title":"Mediterr. J. Hematol. Infect. Dis."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1097\/MED.0b013e3283591502","article-title":"Hypoparathyroidism: From diagnosis to treatment","volume":"19","author":"Soliman","year":"2012","journal-title":"Curr. Opin. Endocrinol. Diabetes Obes."},{"key":"ref_42","unstructured":"World Health Organization (1994). Assessment of Fracture Risk and Its Application to Screening for Postmenopausal Osteoporosis: Report of a WHO Study Group [Meeting Held in Rome from 22 to 25 June 1992], World Health Organization."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1886","DOI":"10.1182\/blood-2009-09-243154","article-title":"Overview on practices in thalassemia intermedia management aiming for lowering complication rates across a region of endemicity: The OPTIMAL CARE study","volume":"115","author":"Taher","year":"2010","journal-title":"Blood"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.3324\/haematol.13500","article-title":"Treatment of hepatitis C in patients with thalassemia","volume":"93","author":"Angelucci","year":"2008","journal-title":"Haematologica"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"4064","DOI":"10.1182\/blood.V114.22.4064.4064","article-title":"Evaluation of Liver Disease in a Cohort of Patients Affected by Thalassemia Intermedia","volume":"114","author":"Motta","year":"2009","journal-title":"Blood"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1007\/s00268-017-4185-2","article-title":"Thromboembolic Events Following Splenectomy: Risk Factors, Prevention, Management and Outcomes","volume":"42","author":"Rottenstreich","year":"2018","journal-title":"World J. Surg."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Kalamara, T.V., Dodos, K., and Vlachaki, E. (2023). Splenectomy is significantly associated with thrombosis but not with pulmonary hypertension in patients with transfusion-dependent thalassemia: A meta-analysis of observational studies. Front. Med., 10.","DOI":"10.3389\/fmed.2023.1259785"},{"key":"ref_48","first-page":"s124","article-title":"Extramedullary haematopoiesis correlates with genotype and absence of cardiac iron overload in polytransfused adults with thalassaemia","volume":"12","author":"Ricchi","year":"2014","journal-title":"Blood Transfus."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1001\/archinte.1981.00340080073017","article-title":"Spinal cord compression in thalassemia. Report of 12 cases and recommendations for treatment","volume":"141","author":"Issaragrisil","year":"1981","journal-title":"Arch. Intern. Med."},{"key":"ref_50","first-page":"e292","article-title":"Erythropoiesis is not equally suppressed in transfused males and females with \u03b2 thalassemia major: Are there clinical implications?","volume":"100","author":"Hapgood","year":"2015","journal-title":"Haematologica"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1182\/blood-2012-12-471441","article-title":"Transfusion suppresses erythropoiesis and increases hepcidin in adult patients with \u03b2-thalassemia major: A longitudinal study","volume":"122","author":"Pasricha","year":"2013","journal-title":"Blood"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1113\/jphysiol.2010.195057","article-title":"Regulation of erythropoietin production","volume":"589","author":"Jelkmann","year":"2011","journal-title":"J. Physiol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1111\/j.1365-2141.2010.08220.x","article-title":"Age-related complications in treatment-naive patients with thalassaemia intermedia","volume":"150","author":"Taher","year":"2010","journal-title":"Br. J. Haematol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1161\/CIRCULATIONAHA.113.002124","article-title":"Prevalence and risk factors for pulmonary arterial hypertension in a large group of \u03b2-thalassemia patients using right heart catheterization: A Webthal study","volume":"129","author":"Derchi","year":"2014","journal-title":"Circulation"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.1136\/hrt.2005.079970","article-title":"Splenectomy: A strong risk factor for pulmonary hypertension in patients with thalassaemia","volume":"92","author":"Phrommintikul","year":"2006","journal-title":"Heart"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"e221856","DOI":"10.1148\/radiol.221856","article-title":"Quantification of Liver Iron Overload with MRI: Review and Guidelines from the ESGAR and SAR","volume":"307","author":"Reeder","year":"2023","journal-title":"Radiology"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Dos Santos, L., Bertoli, S.R., \u00c1vila, R.A., and Marques, V.B. (2022). Iron overload, oxidative stress and vascular dysfunction: Evidences from clinical studies and animal models. Biochim Biophys Acta Gen. Subj., 1866.","DOI":"10.1016\/j.bbagen.2022.130172"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"5124553","DOI":"10.1155\/2022\/5124553","article-title":"Role of Iron-Related Oxidative Stress and Mitochondrial Dysfunction in Cardiovascular Diseases","volume":"2022","author":"Yan","year":"2022","journal-title":"Oxidative Med. Cell Longev."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1183\/09059180.00007211","article-title":"Portopulmonary hypertension and hepatopulmonary syndrome: A clinician-oriented overview","volume":"21","author":"Altamirano","year":"2012","journal-title":"Eur. Respir. Rev."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2254","DOI":"10.1056\/NEJMra0804411","article-title":"Pulmonary complications of sickle cell disease","volume":"359","author":"Gladwin","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"5","DOI":"10.4274\/Tjh.2014.0032","article-title":"\u03b2-Thalassemia Intermedia: A Bird\u2019s-Eye View","volume":"31","author":"Haddad","year":"2014","journal-title":"Turk. J. Haematol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1002\/ajh.20603","article-title":"Pulmonary hypertension and \u03b2-thalassemia major: Report of a case, its treatment, and a review of the literature","volume":"81","author":"Tam","year":"2006","journal-title":"Am. J. Hematol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"3794","DOI":"10.1182\/blood-2010-11-319152","article-title":"Risk factors and mortality associated with an elevated tricuspid regurgitant jet velocity measured by Doppler-echocardiography in thalassemia: A Thalassemia Clinical Research Network report","volume":"118","author":"Morris","year":"2011","journal-title":"Blood"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1961","DOI":"10.1161\/CIRCULATIONAHA.109.874487","article-title":"Cardiac T2* magnetic resonance for prediction of cardiac complications in thalassemia major","volume":"120","author":"Kirk","year":"2009","journal-title":"Circulation"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2253","DOI":"10.1161\/CIRCULATIONAHA.111.050773","article-title":"Iron overload cardiomyopathy in clinical practice","volume":"124","author":"Kremastinos","year":"2011","journal-title":"Circulation"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1093\/ehjci\/jex012","article-title":"Prediction of cardiac complications for thalassemia major in the widespread cardiac magnetic resonance era: A prospective multicentre study by a multi-parametric approach","volume":"19","author":"Pepe","year":"2018","journal-title":"Eur. Heart J. Cardiovasc. Imaging"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Meloni, A., Pistoia, L., Gamberini, M.R., Cuccia, L., Lisi, R., Cecinati, V., Ricchi, P., Gerardi, C., Restaino, G., and Righi, R. (2023). Multi-Parametric Cardiac Magnetic Resonance for Prediction of Heart Failure Death in Thalassemia Major. Diagnostics, 13.","DOI":"10.3390\/diagnostics13050890"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1586\/erc.11.112","article-title":"Aging is a primary risk factor for cardiac arrhythmias: Disruption of intracellular Ca2+ regulation as a key suspect","volume":"9","author":"Hatch","year":"2011","journal-title":"Expert Rev. Cardiovasc. Ther."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1002\/agm2.12015","article-title":"Atrial fibrillation in aging population","volume":"1","author":"Chen","year":"2018","journal-title":"Aging Med."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1016\/j.jacc.2007.09.064","article-title":"Atrial fibrosis: Mechanisms and clinical relevance in atrial fibrillation","volume":"51","author":"Burstein","year":"2008","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"22","DOI":"10.20517\/jca.2024.12","article-title":"Aging-associated mechanisms of atrial fibrillation progression and their therapeutic potential","volume":"4","author":"Zhao","year":"2024","journal-title":"J. Cardiovasc. Aging"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1001\/archinte.1974.00320160137012","article-title":"The cardiovascular manifestations of sickle cell disease","volume":"133","author":"Lindsay","year":"1974","journal-title":"Arch. Intern. Med."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1161\/01.CIR.88.3.1127","article-title":"Left ventricular diastolic Doppler characteristics in beta-thalassemia major","volume":"88","author":"Kremastinos","year":"1993","journal-title":"Circulation"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/0002-8703(72)90445-0","article-title":"Cardiovascular effects of anemia","volume":"83","author":"Varat","year":"1972","journal-title":"Am. Heart J."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"2005","DOI":"10.1136\/hrt.2010.204834","article-title":"Echocardiographic assessment of raised pulmonary vascular resistance: Application to diagnosis and follow-up of pulmonary hypertension","volume":"96","author":"Dahiya","year":"2010","journal-title":"Heart"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1196\/annals.1345.003","article-title":"Changing patterns of thalassemia worldwide","volume":"1054","author":"Vichinsky","year":"2005","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"e2018048","DOI":"10.4178\/epih.e2018048","article-title":"The survival rate of patients with beta-thalassemia major and intermedia and its trends in recent years in Iran","volume":"40","author":"Adineh","year":"2018","journal-title":"Epidemiol. Health"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1111\/ejh.13410","article-title":"The changing epidemiology of the ageing thalassaemia populations: A position statement of the Thalassaemia International Federation","volume":"105","author":"Farmakis","year":"2020","journal-title":"Eur. J. Haematol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1002\/ajh.22223","article-title":"Pancreatic iron and glucose dysregulation in thalassemia major","volume":"87","author":"Noetzli","year":"2012","journal-title":"Am. J. Hematol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"2830","DOI":"10.2337\/dc20-0908","article-title":"The Close Link of Pancreatic Iron With Glucose Metabolism and With Cardiac Complications in Thalassemia Major: A Large, Multicenter Observational Study","volume":"43","author":"Pepe","year":"2020","journal-title":"Diabetes Care"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"5305","DOI":"10.1210\/en.2004-0392","article-title":"Oxidative stress, \u03b2-cell apoptosis, and decreased insulin secretory capacity in mouse models of hemochromatosis","volume":"145","author":"Cooksey","year":"2004","journal-title":"Endocrinology"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"S127","DOI":"10.3109\/09553000903347880","article-title":"New concept in natural history and management of diabetes mellitus in thalassemia major","volume":"33","author":"Chatterjee","year":"2009","journal-title":"Hemoglobin"},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Venou, T.M., Kyriakidis, F., Barmpageorgopoulou, F., Theodoridou, S., Vyzantiadis, A., Klonizakis, P., Gavriilaki, E., and Vlachaki, E. (2025). Risk Factors for Impaired Glucose Metabolism in Transfusion-Dependent Patients with \u03b2-Thalassemia: A Single-Center Retrospective Observational Study. Hematol. Rep., 17.","DOI":"10.3390\/hematolrep17010006"},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Palumbo, G.A., Galimberti, S., Barcellini, W., Cilloni, D., Di Renzo, N., Elli, E.M., Finelli, C., Maurillo, L., Ricco, A., and Musto, P. (2021). From Biology to Clinical Practice: Iron Chelation Therapy With Deferasirox. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.752192"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"4911205","DOI":"10.1155\/2022\/4911205","article-title":"Iron Chelators in Treatment of Iron Overload","volume":"2022","author":"Entezari","year":"2022","journal-title":"J. Toxicol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"e70165","DOI":"10.1002\/hem3.70165","article-title":"Luspatercept versus mitapivat for non-transfusion-dependent \u03b2-thalassemia: Dare to compare?","volume":"9","author":"Musallam","year":"2025","journal-title":"Hemasphere"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/S0140-6736(25)00635-X","article-title":"Mitapivat in adults with non-transfusion-dependent \u03b1-thalassaemia or \u03b2-thalassaemia (ENERGIZE): A phase 3, international, randomised, double-blind, placebo-controlled trial","volume":"406","author":"Taher","year":"2025","journal-title":"Lancet"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"e733","DOI":"10.1016\/S2352-3026(22)00208-3","article-title":"Luspatercept for the treatment of anaemia in non-transfusion-dependent \u03b2-thalassaemia (BEYOND): A phase 2, randomised, double-blind, multicentre, placebo-controlled trial","volume":"9","author":"Taher","year":"2022","journal-title":"Lancet Haematol."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/18\/6602\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:48:55Z","timestamp":1760035735000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/18\/6602"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,19]]},"references-count":88,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["jcm14186602"],"URL":"https:\/\/doi.org\/10.3390\/jcm14186602","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,19]]}}}