Thalassemia: Common Clinical Queries in Management

  • Ashutosh LalEmail author
  • Deepak Bansal
Review Article


Beta thalassemia major (TM) is the most frequent form of transfusion-dependent inherited anemia in India. The thalassemia syndromes exhibit enormous variability in their genetic basis and phenotypic expression. The authors recommend that the diagnosis of TM or non-transfusion-dependent thalassemia (NTDT) should not be based on a one-time assessment. Many patients have a chronic anemia that is not severe enough to justify regular transfusions, but the clinical course can evolve with age. Continued observation may reveal that some patients who are considered NTDT will benefit from transfusions later in life. Clinical decision making can be influenced by the perceived difficulty in access to a safe blood supply and the cost of therapy. Here, authors present selected case scenarios that address common issues in the management of TM or NTDT. The recommendations are based on published evidence where available or on the authors’ shared experience. Among the topics under discussion are deciding when to start regular transfusions, the role of hydroxyurea in TM, the procedure for blood administration, the use of deferasirox for chelation and monitoring of side effects, the role of splenectomy, and the prospects for gene therapy. In order to achieve an optimal outcome with blood transfusions and chelation therapy over the lifetime, it is essential to adhere to the current guidelines for the management of thalassemia.


Thalassemia Transfusion Iron Chelation 


Authors’ Contribution

The authors contributed to formulation of questions and discussion of recommended management. DB is the guarantor of this paper.

Compliance with Ethical Standards

Conflict of Interest



  1. 1.
    Cappellini MD, Cohen A, Porter J, Taher A, Viprakasit V. Guidelines for the Management of Transfusion Dependent Thalassaemia (TDT) [Internet], 3rd ed. Nicosia (CY): Thalassaemia International Federation; 2014. Available at: Accessed 30 Oct 2017.
  2. 2.
    Lal A, Sheth S, Gilbert S, Kwiatkowski JL. Thalassemia management checklists: quick reference guides to reduce disparities in the care of patients with transfusion-dependent thalassemia. Blood. 2018;132:2233.CrossRefGoogle Scholar
  3. 3.
    Olivieri NF, Brittenham GM. Management of the thalassemias. Cold Spring Harb Perspect Med. 2013;3:a011767.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Badens C, Joly P, Agouti I, et al. Variants in genetic modifiers of β-thalassemia can help to predict the major or intermedia type of the disease. Haematologica. 2011;96:1712–4.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Cao A, Galanello R. Beta-thalassemia. Genet Med. 2010;12:61–76.CrossRefPubMedGoogle Scholar
  6. 6.
    Weatherall DJ. Phenotype-genotype relationships in monogenic disease: lessons from the thalassaemias. Nat Rev Genet. 2001;2:245–55.CrossRefPubMedGoogle Scholar
  7. 7.
    Taher AT, Musallam KM, Cappellini MD, Weatherall DJ. Optimal management of β thalassaemia intermedia. Br J Haematol [Internet]. 2011. Available at: Accessed 3 Feb 2011.
  8. 8.
    Piga A, Serra M, Longo F, et al. Changing patterns of splenectomy in transfusion-dependent thalassemia patients. Am J Hematol. 2011;86:808–10.CrossRefPubMedGoogle Scholar
  9. 9.
    Bansal D. Splenectomy for β-thalassemia major in resource challenged settings: often a hobson’s choice! Indian J Pediatr. 2015;82:1082–3.CrossRefPubMedGoogle Scholar
  10. 10.
    Olivieri NF, Muraca GM, O’Donnell A, Premawardhena A, Fisher C, Weatherall DJ. Studies in haemoglobin E beta-thalassaemia. Br J Haematol. 2008;141:388–97.CrossRefPubMedGoogle Scholar
  11. 11.
    Bradai M, Abad MT, Pissard S, Lamraoui F, Skopinski L, de Montalembert M. Hydroxyurea can eliminate transfusion requirements in children with severe {beta}-thalassemia. Blood. 2003;102:1529–30.CrossRefPubMedGoogle Scholar
  12. 12.
    Musallam KM, Taher AT, Cappellini MD, Sankaran VG. Clinical experience with fetal hemoglobin induction therapy in patients with β-thalassemia. Blood. 2013;121:2199–212.CrossRefPubMedGoogle Scholar
  13. 13.
    Goldberg SL, Giardina PJ, Chirnomas D, Esposito J, Paley C, Vichinsky E. The palatability and tolerability of deferasirox taken with different beverages or foods. Pediatr Blood Cancer. 2013;60:1507–12.CrossRefPubMedGoogle Scholar
  14. 14.
    Taher A, Cappellini MD, Vichinsky E, et al. Efficacy and safety of deferasirox doses of >30 mg/kg per d in patients with transfusion-dependent anaemia and iron overload. Br J Haematol. 2009;147:752–9.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Cohen AR, Glimm E, Porter JB. Effect of transfusional iron intake on response to chelation therapy in -thalassemia major. Blood. 2008;111:583–7.CrossRefPubMedGoogle Scholar
  16. 16.
    Aydinok Y, Kattamis A, Cappellini MD, et al; HYPERION Investigators. Effects of deferasirox-deferoxamine on myocardial and liver iron in patients with severe transfusional iron overload. Blood. 2015;125:3868–77.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Lal A, Porter J, Sweeters N, et al. Combined chelation therapy with deferasirox and deferoxamine in thalassemia. Blood Cells Mol Dis. 2013;50:99–104.CrossRefPubMedGoogle Scholar
  18. 18.
    Totadri S, Bansal D, Bhatia P, Attri SV, Trehan A, Marwaha RK. The deferiprone and deferasirox combination is efficacious in iron overloaded patients with β-thalassemia major: a prospective, single center, open-label study. Pediatr Blood Cancer. 2015;62:1592–6.CrossRefPubMedGoogle Scholar
  19. 19.
    Chang H-H, Lu M-Y, Liao Y-M, et al. Improved efficacy and tolerability of oral deferasirox by twice-daily dosing for patients with transfusion-dependent β-thalassemia. Pediatr Blood Cancer. 2011;56:420–4.CrossRefPubMedGoogle Scholar
  20. 20.
    Cappellini MD. Long-term efficacy and safety of deferasirox. Blood Rev. 2008;22:S35–41.CrossRefPubMedGoogle Scholar
  21. 21.
    Díaz-García JD, Gallegos-Villalobos A, Gonzalez-Espinoza L, Sanchez-Niño MD, Villarrubia J, Ortiz A. Deferasirox nephrotoxicity—the knowns and unknowns. Nat Rev Nephrol. 2014;10:574–86.CrossRefPubMedGoogle Scholar
  22. 22.
    Food and Drug Adminstration. Exjade: full prescribing information [Internet]. 2019. Available at: Accessed 28 Jul 2019.
  23. 23.
    Lal A, Wong TE, Andrews J, et al. Transfusion practices and complications in thalassemia. Transfusion. 2018;58:2826–35.CrossRefPubMedGoogle Scholar
  24. 24.
    Vichinsky E, Neumayr L, Trimble S, et al. Transfusion complications in thalassemia patients: a report from the Centers for Disease Control and Prevention (CME). Transfusion. 2014;54:972–81.CrossRefPubMedGoogle Scholar
  25. 25.
    Dhawan HK, Kumawat V, Marwaha N, et al. Alloimmunization and autoimmunization in transfusion dependent thalassemia major patients: study on 319 patients. Asian J Transfus Sci. 2014;8:84–8.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Pahuja S, Pujani M, Gupta SK, Chandra J, Jain M. Alloimmunization and red cell autoimmunization in multitransfused thalassemics of Indian origin. Hematology. 2010;15:174–7.CrossRefPubMedGoogle Scholar
  27. 27.
    Fucharoen S, Weatherall DJ. The hemoglobin E thalassemias. Cold Spring Harb Perspect Med. 2012;2:a011734.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Olivieri NF, Pakbaz Z, Vichinsky E. Hb E/beta-thalassaemia: a common & clinically diverse disorder. Indian J Med Res. 2011;134:522–31.PubMedPubMedCentralGoogle Scholar
  29. 29.
    Colah RB, Gorakshakar A. Control of thalassemia in India. Thalassemia Reports [Internet] 2014;4. Available at: Accessed 30 Sept 2014.
  30. 30.
    Thompson AA, Walters MC, Kwiatkowski J, et al. Gene therapy in patients with transfusion-dependent β-thalassemia. New Engl J Med. 2018;378:1479–93.CrossRefPubMedGoogle Scholar
  31. 31.
    McClain LE, Flake AW. In utero stem cell transplantation and gene therapy: recent progress and the potential for clinical application. Best Pract Res Clin Obstet Gynaecol. 2016;31:88–98.CrossRefGoogle Scholar
  32. 32.
    Wang H, Georgakopoulou A, Psatha N, et al. In vivo hematopoietic stem cell gene therapy ameliorates murine thalassemia intermedia. J Clin Invest. 2019;129:598–615.CrossRefPubMedGoogle Scholar
  33. 33.
    Anurathapan U, Hongeng S, Pakakasama S, et al. Hematopoietic stem cell transplantation for homozygous β-thalassemia and β-thalassemia/hemoglobin E patients from haploidentical donors. Bone Marrow Transplant. 2016;51:813–8.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Sun Q, Wu B, Lan H, et al. Haploidentical haematopoietic stem cell transplantation for thalassaemia major based on an FBCA conditioning regimen. Br J Haematol. 2018;182:554–8.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Fung EB, Aguilar C, Micaily I, Haines D, Lal A. Treatment of vitamin D deficiency in transfusion-dependent thalassemia. Am J Hematol. 2011;86:871–3.CrossRefPubMedGoogle Scholar
  36. 36.
    Office of Dietary Supplements. Calcium: fact sheet for health professionals [Internet]. Available at: Accessed 28 Jul 2019.
  37. 37.
    Centers for Disease Control. Vaccination of Adults with Asplenia [Internet]. 2019. Available at: Accessed 28 Jul 2019.

Copyright information

© Dr. K C Chaudhuri Foundation 2019

Authors and Affiliations

  1. 1.Hematology/Oncology, Department of PediatricsUniversity of CaliforniaSan FranciscoUSA
  2. 2.Pediatric Hematology/Oncology Unit, Department of PediatricsPostgraduate Institute of Medical Education and ResearchChandigarhIndia

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