Published: 2021-05-27

The key complications of beta thalassemia major: a review and update

Jia Ying Chiew, Jeevitha Thiruchelvam, Mohd Azlan Bin Rahmat, Stephanie Priscilla William, Zikril Iman Bin Shafien, Kishore Gopal Banerjee


Thalassemia is a heterogeneous group of genetic disorder with the defective synthesis of one or more globin chains. β-thalassemia is a global disease with high prevalence in Africa, Southeast Asia and Mediterranean countries. In Malaysia, the α and β-thalassemia are the commonest. In the articles that we reviewed, transfusion-dependent β-thalassemia is highly associated with complications related to thalassemia such as cardiovascular disease, endocrine disorders, skeletal deformities and others. Following advancements in β-thalassemia major treatment, cardiovascular disease remains the leading cause of mortality in β-thalassemia major patients. Thalassemia-associated cardiac pathology includes several conditions, such as myocardial dysfunction, arrhythmias and atrial fibrillation. Endocrine disorders, caused by iron deposition in the gland, resulting in impaired endocrine function. The commonest presentation is short stature followed by impaired puberty, abnormal thyroid function and diabetes mellitus. Moreover, skeletal complications remain a challenge. The most prevalent complications are malocclusion of the teeth, frontal bossing and chipmunk facies whilst osteoporosis, osteopenia and fracture are seen in a minority of the patient. Although comprehensive care has resulted in long-term survival and good quality of life, poor management will lead to complications that increase the treatment cost. However, genetic study (DNA analysis) examines the deletions and mutations in the α and β-globin-producing genes that help to correct diagnosis and improve management in thalassemia patients.


β-thalassemia major, Hemosiderosis, Cardiomyopathy, Endocrinopathy, Skeletal complications

Full Text:



Arian M, Mirmohammadkhani M, Ghorbani R, Soleimani M. Health-related quality of life (HRQoL) in beta-thalassemia major (β-TM) patients assessed by 36-item short form health survey (SF-36): a meta-analysis. Qual Life Res. 2019;28(2):321-34.

Mohd IH, Muda Z, Othman IS, Mohamed UMN, Teh KH, Thevarajah A, et al. Observational study on the current status of thalassaemia in Malaysia: a report from the Malaysian Thalassaemia Registry. BMJ Open. 2020;10(6):37974.

Galanello R, Origa R. Beta-thalassemia. Orphanet J Rare Dis. 2010;5:11.

Kohne E. Hemoglobinopathies: clinical manifestations, diagnosis, and treatment. Dtsch Arztebl Int. 2011;108(31):532-40.

Meng CY, Esa E, Yacob AM, Ramachandran S, Zakaria Z. Screening for Hemoglobinopathies among Patients in a Government Hospital and Health Clinic in Perlis, Malaysia. J Med Sci Technol. 2014;3(2):82-6.

Shah FT, Sayani F, Trompeter S, Drasar E, Piga A. Challenges of blood transfusions in β-thalassemia. Blood Rev. 2019;37:100588.

Verma M. Genetic disorder Thalassemia : Causes and Prevention. Sociology. 2019;3085(1):2078-80.

Origa R. β-Thalassemia. Genet Med. 2017;19(6):609-19.

Kolios M, Korantzopoulos P, Vlahos AP, Kapsali E, Briasoulis E, Goudevenos JA. Electrocardiographic abnormalities and arrhythmic risk markers in adult patients with beta thalassemia major. Int J Cardiol. 2016;221:932-6.

Russo V, Rago A, Papa AA, Nigro G. Electrocardiographic Presentation, Cardiac Arrhythmias, and Their Management in β-Thalassemia Major Patients. Ann Noninvasive Electrocardiol. 2016;21(4):335-42.

Borgna PC, Gamberini MR. Complications of thalassemia major and their treatment. Expert Rev Hematol. 2011;4(3):353-66.

Kremastinos DT, Farmakis D, Aessopos A, Hahalis G, Hamodraka E, Tsiapras D, et al. Beta-thalassemia cardiomyopathy: history, present considerations, and future perspectives. Circ Heart Fail. 2010;3(3):451-8.

Hamed AA, Elguindy W, Elhenawy YI, Ibrahim RH. Early Cardiac Involvement and Risk Factors for the Development of Arrhythmia in Patients With β-Thalassemia Major. J Pediatr Hematol Oncol. 2016;38(1):5-11.

Pennell DJ, Udelson JE, Arai AE, Bozkurt B, Cohen AR, Galanello R, et al. Cardiovascular function and treatment in β-thalassemia major: a consensus statement from the American Heart Association. Circulation. 2013;128(3):281-308.

Motta I, Mancarella M, Marcon A, Vicenzi M, Cappellini MD. Management of age-associated medical complications in patients with β-thalassemia. Expert Rev Hematol. 2020;13(1):85-94.

Muhamedamin HK, Mohammad ZM. Prevalence of Pulmonary Hypertension among Patients with β- thalassemia Major in Erbil Province -Iraq. Diyala J Med. 2019;16(2):17-30.

Ehsan H, Wahab A, Anwer F, Iftikhar R, Yousaf MN. Prevalence of Transfusion Transmissible Infections in Beta-Thalassemia Major Patients in Pakistan: A Systematic Review. Cureus. 2020;12(8):10070.

Srisukh S, Ongphiphadhanakul B, Bunnag P. Hypogonadism in thalassemia major patients. J Clin Transl Endocrinol. 2016;5:42-5.

Sanctis V, Elsedfy H, Soliman AT, Elhakim IZ, Soliman NA, Elalaily R, Kattamis C. Endocrine profile of β-thalassemia major patients followed from childhood to advanced adulthood in a tertiary care center. Indian J Endocrinol Metab. 2016;20(4):451-9.

Wong SH, Omar J, Ismail TST. Multiple Endocrinologic Complications in Thalassemia Major. The Korean J Clinical Lab Sci. 2017;49(4): 495-7.

Abdulzahra MS, Al-Hakeim HK, Ridha MM. Study of the effect of iron overload on the function of endocrine glands in male thalassemia patients. Asian J Transfus Sci. 2011;5(2):127-31.

Merchant RH, Shirodkar A, Ahmed J. Evaluation of growth, puberty and endocrine dysfunctions in relation to iron overload in multi transfused Indian thalassemia patients. Indian J Pediatr. 2011;78(6):679-83.

Tan KA, Lum SH, Yahya A, Krishnan S, Jalaludin MY, Lee WS. Prevalence of growth and endocrine disorders in Malaysian children with transfusion-dependent thalassaemia. Singapore Med J. 2019;60(6):303-8.

Hashemi A, Ghilian R, Golestan M, Akhavan Ghalibaf M, Zare Z, Dehnhani MA. The study of growth in thlassemia patients and its correlation with serum ferritin level. Iranian J Peadiatrics Hematol Oncol. 2011;1(4):147-51.

Shamaoon M, Nawaz J, Ahsan M. Β-Thalassemia Major; Frequency of Short Stature in Children With Β-Thalassemia Major Receiving Multiple Blood Transfusion Original Prof-4721. The Professional Med J Professional Med J. 2018;25(6):823-7.

Aslam MS, Roshan E, Iqbal A, Shahid M. Frequency of Short Stature in -Thalassemia Major Patients. Pak Armed Forces Med J. 2013;63(4): 503-7.

Soliman AT, Yassin MA, Sanctis V. Final adult height and endocrine complications in young adults with β-thalassemia major (TM) who received oral iron chelation (OIC) in comparison with those who did not use OIC. Acta Biomed. 2018;89(2):27-32.

Sharma R, Seth A, Chandra J, Gohain S, Kapoor S, Singh P, Pemde H. Endocrinopathies in adolescents with thalassaemia major receiving oral iron chelation therapy. Paediatr Int Child Health. 2016;36(1):22-7.

Sinharay M, Mitra S, Dasgupta A. Effect of Iron Overload on Gonadotrophins and Organ Sex Steroids in Pubertal Thalassemia Patients. Int J Current Res Rev. 2011;9(23):15-21.

Sanctis V, Soliman AT, Yassin MA, Maio S, Daar S, Elsedfy H, et al. Hypogonadism in male thalassemia major patients: pathophysiology, diagnosis and treatment. Acta Biomed. 2018;89(2):6-15.

Soliman AT, Al Yafei F, Al-Naimi L, Almarri N, Sabt A, Yassin M, De Sanctis V. Longitudinal study on thyroid function in patients with thalassemia major: High incidence of central hypothyroidism by 18 years. Indian J Endocrinol Metab. 2013;17(6):1090-5.

Upadya SH, Rukmini MS, Sundararajan S, Baliga BS, Kamath N. Thyroid Function in Chronically Transfused Children with Beta Thalassemia Major: A Cross-Sectional Hospital Based Study. Int J Pediatr. 2018;9071213.

Eshragi P, Tamaddoni A, Zarifi K, Mohammadhasani A, Aminzadeh M. Thyroid function in major thalassemia patients: Is it related to height and chelation therapy? Caspian J Intern Med. 2011;2(1):189-93.

He LN, Chen W, Yang Y, Xie YJ, Xiong ZY, Chen DY, et al. Elevated Prevalence of Abnormal Glucose Metabolism and Other Endocrine Disorders in Patients with β-Thalassemia Major: A Meta-Analysis. Biomed Res Int. 2019;6573497.

Barnard M, Tzoulis P. Diabetes and thalassaemia. Thalassemia Reports. 2013;3(1):18.

Bhat KG, Periasamy PK. Effect of long-term transfusion therapy on the glycometabolic status and pancreatic Beta cell function in patients with Beta thalassemia major. J Family Med Prim Care. 2014;3(2):119-23.

Bazi A, Sharifi RJ, Rostami D, Sargazi AO, Safa A. Diabetes Mellitus in Thalassaemia Major Patients: A Report from the Southeast of Iran. J Clin Diagn Res. 2017;11(5):1-4.

Karuppiah D. Evaluation and management of diabetes in patients with thalassaemia major. J Ceylon College of Physicians. 2016;46(1):39.

Karakas S, Tellioglu AM, Bilgin M, Omurlu IK, Caliskan S, Coskun S. Craniofacial Characteristics of Thalassemia Major Patients. Eurasian J Med. 2016;48(3):204-8.

Gupta DK, Singh SP, Utreja A, Verma S. Prevalence of malocclusion and assessment of treatment needs in β-thalassemia major children. Prog Orthod. 2016;17:7.

Toman HA, Hassan R, Hassan R, Nasir A. Craniofacial deformities in transfusion-dependent thalassemia patients in Malaysia: prevalence and effect of treatment. Southeast Asian J Trop Med Public Health. 2011;42(5):1233-40.

Venkatesh BN, Amitha H. Radiological study of Oral and Craniofacial Findings in β Thalassaemic Children Undergoing Blood Transfusion. Int J Scientific Study. 2014;2(1):11-5.

Saki N, Abroun S, Salari F, Rahim F, Shahjahani M, Javad MA. Molecular Aspects of Bone Resorption in β-Thalassemia Major. Cell J. 2015;17(2):193-200.

Yigitoglu PH, Guzel R. Osteoporosis in Thalassemia Major. Turk Osteoporoz Dergisi. 2012;18(3):89-91.

Perisano C, Marzetti E, Spinelli MS, Calla CA, Graci C, Maccauro G. Physiopathology of Bone Modifications in β-Thalassemia. Anemia. 2012;320737.

Sutipornpalangkul W, Janechetsadatham Y, Siritanaratkul N, Harnroongroj T. Prevalence of fractures among Thais with Thalassaemia syndromes. Singapore Med J. 2010;51(10):817-21.

Chen YG, Lu CS, Lin TY, Lin CL, Tzeng HE, Tsai CH. Risk of fracture in transfusion-naïve thalassemia population: A nationwide population-based retrospective cohort study. Bone. 2018;106:121-5.

Pellegrino F, Zatelli MC, Bondanelli M, Carnevale A, Cittanti C, Fortini M, et al. Dual-energy X-ray absorptiometry pitfalls in Thalassemia Major. Endocrine. 2019;65(3):469-82.