• Dharmesh Chandra Sharma Associate Blood Transfusion Officer (ABTO), Incharge Component & Aphaeresis Unit, Blood Bank, G. R. Medical College, Gwalior. India
  • Anita Arya Medical Officer, Blood Bank, G. R. Medical College, Gwalior
  • Purnima Kishor Department of Biochemistry, Jiwaji University, Gwalior
  • Poonam Woike Resident, Department of Pathology, G. R. Medical College, Gwalior
  • Jyoti Bindal Professor and HOD, Department of Obstetrics & Gynecology, G. R. Medical College, Gwalior
Keywords: Thalassemia, Hemoglobinopathies, Bone Marrow Transplant, Gene Therapy


Thalassemia’s are genetic disorders inherited from a person’s parents. Thalassemia’s are prevalent worldwide with 25,000 deaths in 2013.Highest rates are in the Mediterranean, Italy, Greece, Turkey, West Asia, North Africa, South Asian, and Southeast Asia. The β-thalassemia major is the most severe form and the affected children are dependent on regular blood transfusions for survival. One of the major complications in chronically transfused patients is development of irregular antibodies and in this situation; further transfusion of compatible red cell is difficult. Hemoglobinopathies imply abnormalities in the globin proteins themselves. Health complications are mostly found in thalassemia major and intermediate patients. Signs and symptoms include severe anemia, poor growth and skeletal abnormalities during infancy. Untreated thalassemia major eventually leads to death, usually by heart failure. Diagnosis by hematologic tests, hemoglobin electrophoresis, and DNA analysis. Individuals with severe thalassemia require blood transfusion, drug therapy i.e. deferoxamine, deferasirox, deferiprone, and bone marrow transplant. Bone Marrow Transplant (BMT) is still remains the only definitive cure available for patients with Thalassemia. Gene therapy for β- Thalassemia is still on trial and a hope for future. Genetic studies (DNA analysis) to investigate deletions and mutations in the alpha- and beta-globin-producing gene help in correct diagnosis and improved management in thalassemic patients. This topic will review the clinical features of thalassemia while focusing on pathophysiology, clinical features, complication, management, screening and diagnosis.


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1. Cooley TB, Lee P. A series of cases of splenomegaly in children with anemia and peculiar bone changes. Trans Am Pediatr Soc 1925; 37:29-30
2. Cooley TB, Witwer ER, Lee P (1927) Anemia in children with splenomegaly and peculiar change in bones: report of case Am J Dis Child 34: 347-363.
3. Bradford W.L. and Dye J. (1936). Observations on the morphology of the crythmytes in Mediterranean disease thalassemia (Erythroblastic anemia of Cooley). J. Pediatr. 9(3):12-13.
4. "What Are Thalassemia?” NHLBI. July 3, 2012. Retrieved 5 September 2016
5. What Causes Thalassemia’s? NHLBI. July 3, 2012.Retrieved 5 September 2016.
6. John NL. The thalassemia and related disorders: Quantitative disorders of hemoglobin synthesis; Wintrobe’s Clinical Hematology, tenth edition, Vol. I, chapter 1999 53:1405–1448.
7. Global Burden of Disease Study 2013. Lancet (London England) 2013; 386(9995):743-899.
8. GBD 2013 Mortality and Causes of Death, Collaborations (17 December 2014). Global regional and national agesex specific all cause and cause-specific mortality for 240 causes of death,1990- 2013: a systematic analysis for the Global Burden of Disease Study 2013.Lancet.385:117-71
9. CLIN. Methods in Ped.Jaypee Brothers Publishers.2005. p.21.ISBN 9788171798087.
10. How Are Thalassemia Diagnosed? NHLBI.July 3, 2012.Retrieved 5 September 2016.
11. Thuret I (2000) Therapeutic management of patients with thalassemia major. Bull Soc Pathol Exot 94:95–97
12. Weiner M, Kartpatkin M, Hart D et l (1978) Cooley’s anemia: High transfusion regimen and chelation therapy. Results and prospective. J Paediatr 92:653–658
13. Proter JB (1997) Practical management of iron overload. Curr Opin Hematol 4:436–441
14. Graziano JH, Markenson A, Miller DR et al (1978) Chelation therapy in β-thalassemia major intravenous and subcutaneous desferoxime. J Paediatr 92:646–651
15. Cazzola M, Stefeno PD, Panchio L et al (1995) Relationship between transfusion regimen and suppression of erythropoiesis in β-thalassemia major. British J Hematology 89:473–478
16. Hollan SR (1997) Transfusion associated iron overload. Curr Opin Hematol 4:436–441
17. Angelucci E. Hematopoietic stem cell transplantation in thalassemia. Hematology Am Soc Hematol Educ Program 2010:456-62.
18. Cappellini MD et al (editors). Guidelines for the management of transfusion dependent Thalassemia (TDT).3rd Edition chapter 12. (Angelucci E, Srivastava A and Usai S) Haemopoitic Stem Cell Transplant. Publisher: Thalassemia International Federation ©2014 Team up Creations Ltd 14 Othonos str., 1016 Nicosia.
19. John P. Greer JP, Arber DA, Glader B, et al. Wintrobe's Clinical Hematology 2013. ISBN 9781451172683
20. Modiano G, Morpugo G, Terrenato L, etal. Protection against malaria morbidity: Near –fixation of the alphathalassemia in a Nepalese population. Am J HumanGentic.1991;48(2):390-7.
21. Murtaza Mustafa, A. Thiru, E M. IIIzam, H. Firdaus, A M. Sharifa, K. Fairrul, M K. Nang. Pathophysiology, Clinical Manifestations, and Carrier Detection in halassemia IOSR Journal of Dental and Medical Sciences .Volume 15, Issue 11 Ver. VII (November. 2016), PP 122-126 DOI: 10.9790/0853-151107122126
22. Modiano G, Morpugo G, Terrenato L, etal. Protection against malaria morbidity:Near –fixation of the alphathalassemia in a Nepalese population. Am J Human Gentic. 1991;48(2):390-7.
23. Terrenato L, Shrestha S, Dixit K A, etal. Decreased malaria morbidity in the Tharu people compared to sympatric populations in Nepal.Ann Trop Med Parasitol. 1988;82(1):1-11.
24. Goljan E. Pathology, 2nd ed. Mosby Elsevier, Rapid Review Series.
25. Thalassemia (in Thai), Department of Medical Sciences. September 2011.Archieved from the original on 2011-09-25.
26. HaddowJE.Couple screening to avoid thalassemia: successful in Iran and instructive for us. J MedScreen.2005;12(2):55-56.
27. SamavatA,Modell B. Iranian national thalassemia screening program. BMJ.2004;329:1134-37.
28. MoafiA,ValianS,NikyarZ,etal.Prev alence of minor beta thalassemia based on RBC indices.Int J HematolOnchol Stem Cell. Res.2010;23-27.
29. Kumar R, Sagar C, Sharma D, Kishor P -globin genes: mutation hot-spots in the global thalassemia belt. Hemoglobin. 2015; 39(1):1-8. doi: 10.3109/03630269.2014.985831. Epub 2014 Dec 19.
30. Nathan, D.G. & Oski, F.A. (1993). Hematology of infancy and childhood, 4th ed. Philadelphia: W B Saunders Co.
31. Robbins Basic Pathology, Page No: 428
32. Nathan, D.G. & Gunn, R.B. (1966). Thalassemia: the consequences of unbalanced hemoglobin synthesis. Am J Med, 41(5), p.p. 815-830.
33. Weatherall, D.J. (1998). Thalassemia in the next millennium. Ann N Y Acad Sci, 850, p.p. 1-9.
34. Kumar R, Sharma D C, Kishor P. “Hb E/β-Thalassemia: The Second Most Common Cause of TransfusionDependent Thalassemia in the GwaliorChambal Region of Central India.” Hemoglobin Oct 2012, Vol. 36, No. 5: 485–490. PMID: 22738610
35. Victor et al (1999). Introduction- 1.1- Thallassemia-1.1.3. ClassificationAvailable at https://libraryg.kau.edu.sa/Files/237/Researches/655 09_36921.pdf
36. Howard A P, Alan RC, Patricia-J V G, Haig HK, The Changing Profile of Homozygous β-Thalassemia: Demography, Ethnicity, and Age Distribution of Current North American Patients and Changes in Two Decades Pediatrics March 1996, VOLUME 97 / ISSUE 3
37. Sagar CS, Kumar R, Sharma DC, Kishor P. DNA damage: beta zero versus beta plus thalassemia. Ann Hum Biol. 2015; 42(6):585-8. doi: 10.3109/03014460.2014.990921. Epub 2014 Dec 26.
38. Sagar CS, Kumar R, Sharma DC, Kishor P. Alpha hemoglobin stabilizing protein: Its causal relationship with the severity of beta thalassemia. Blood Cells Mol Dis. 2015 Aug;55(2):104-7. doi:10.1016/j.bcmd.2015.05.005. Epub2015 May 12.
39. Satwani H, Raza J, Alam M, Kidwai A. Endocrine complications in thalassemias; Frequency and association with ferritin levels, P P J, 29(2), 2005, 113-9.
40. Borgna-Pignatti C, Rugolotto S, De Stefano P, et al. Survival and complications in patients with thalassemia major treated with transfusion and deferoxamine. Haematologica. 2004;89 :1187–1193. [PubMed]
41. Cunningham MJ, Macklin EA, Neufeld EJ, et al. Thalassemia Clinical Research N. Complications of betathalassemia major in North merica. Blood. 2004; 104:34–
9. [PubMed]
42. Cianciulli P (October 2008). "Treatment of iron overload in thalassemia". Pediatr Endocrinol Rev. 6 (Suppl 1): 208– 13. PMID 19337180.
43. http://www.mayoclinic.org/diseases-conditions/thalassemia/symptomscauses/dxc-20261829
44. Vogiatzi, Maria G; Macklin, Eric A; Fung, et al (March 2009). "Bone Disease in Thalassemia: A Frequent and Still Unresolved Problem". Journal of Bone and Mineral Research. 24 (3): 543–557. doi:10.1359/jbmr.080505. ISSN 0884-0431. PMC 3276604 PMID 18505376
45. "Symptoms and causes - Enlarged spleen (splenomegaly) - Mayo Clinic". www.mayoclinic.org. Retrieved 2017-02-02.
46. Soliman, Ashraf T; Kalra, Sanjay; De Sanctis, Vincenzo (2014-11- 01). "Anemia and growth". Indian Journal of Endocrinology and Metabolism. 18 (7). doi:10.4103/2230-8210.145038. PMC 4266864. PMID 25538873.
47. "Thalassemia Complications " . Thalassemia. Open Publishing.Retrieved 27 September 2011.
48. "How Are Thalassemia Diagnosed?". NHLBI. July 3, 2012. Retrieved 5 September 2016.
49. "How Can Thalassemia Be Prevented?". NHLBI. July 3, 2012. Retrieved 5 September 2016.
50. Thalassemia- Lab test on line 1) https://labtestsonline.org/understanding/conditions/thalassemia/start/2
51. Pediatric Thalassemia treatment at e Medicine. http://emedicine.medscape.com/article/958850-treatmen
52. Renzo Galanello and Antonio Cao. Alpha-Thalassemia. Genetics in Medicine (2011) 13, 83–88; doi:10.1097/GIM.0b013e3181fcb468
53. Sonakul D, Fucharoen S. Pulmonary thromboembolism in thalassemic patients. SoutheastAsian J Trop Med Public Health 1992;23:25–28.
54. Lucke T, Pfister S, Durken M. Neurodevelopmental outcome and haematological course of a long-time survivor with homozygous alphathalassaemia: case report and review of the literature. Acta Paediatr 2005;94:1330–1333.
55. Borgna-Pignatti C, Galanello R. Wintrobe's Clinical Hematology. 11.Vol. 42. Lippincott Williams & Wilkins. Philadelphia; 2004. Thalassemia and related disorders: quantitative disorders of hemoglobin synthesis; pp. 1319– 1365.
56. Borgna-Pignatti C. Modern treatment of thalassaemia intermedia. Br J Haematol. 2007;138:291–304. doi: 10.1111/j.1365-2141.2007.06654.x.
57. Renzo Galanello and Raffaella Origa. Beta-Thalassemia Orphanet J Rare Dis. 2010; 5: 11. Published online 2010 May 21. doi: 10.1186/1750-1172-5-11 MCID: PMC2893117
58. Naldini L. 2011. Ex vivo gene transfer and correction for cell-based therapies. Nat Rev Genet 12: 301–315.
59. Rivière I, Dunbar CE, Sadelain M. 2012. Hematopoietic stem cell engineering at a crossroads. Blood 119: 1107–1116.
60. Sabloff M,Chandy M,Wang Z,etal. HLA-matched sibling bone marrow transplantation for β Thalassemia major.Blood.2011;117(5):1745-50.
61. Sodani P,Isgro A,Gaziev J,etal. Tcell depleted hla-haploidenttical stem cell transplantation in thalassemia young patients.Pedtr Reports.2011;3 Suppl 2(Suppl 2):e 13.
62. Sharma DC, Singhal S, Woike P,. Tomar AS,. Rawat N,. Arya A, Gaur R. Red Blood Cells Alloimmunization and Transfusion Strategy in Transfusion Dependent B-Thalassemia Patients IOSR-JDMS Volume 15, Issue 12 Ver. II (December. 2016), PP 10-14 www.iosrjournals.org
63. Orsini A, Boyer G. La talassemia a Marsiglia; dati sulla frequenza ed osservazioni su alcuni aspetti clinici terapeutici ed assistenziali. Il problema sociale della microcitemia e del Morbo di Cooley. Rome 1961
64. Piomelli S, Danoff SJ, Becker MH et al. Prevention of bone malformations and cardiomegaly in Cooley’s anemia by early hypertransfusion regimen. Ann
NY Acad Sci 1969; 165: 427-436.
65. Cazzola M, Borgna-Pignatti C, Locatelli F et al. A moderate transfusion regimen may reduce iron loading in beta-thalassemia major without producing excessive expansion of erythropoiesis. Transfusion 1997; 37: 135-140.
66. Thalassemia International Federation (T.I.F.). Guidelines for the clinical management of thalassemia. 2000.
67. http://www.thalassemia.org.cy
68. Norfolk DR, Williamson LM. Leucodepletion of blood products by filtration. Blood Rev 1995; 9: 7-14.
69. Sharma DC, Ra S, GuptaS and Jain B “Universal Leukoreduction Decreases the Incidence of Febrile Nonhemolytic Transfusion Reactions to Cellular Blood Components: A 5 Year Study. International Blood Research & Reviews, ISSN: 2321–7219,Vol.: 2, Issue.: 6 (Nov.-December)
70. Sharma DC, Rai S, garwal N, Sao S, Gaur A, Sapra R.“Transfusion of neocytes concentrate/pooled neocytes in β-thalassemic patients” Indian Journal of Hematology and Blood Transfusion 24(4): December 2008; 173–177.
71. Sharma DC, Agrawal N , Bindal J, Poonam Woike P, Gaur R. 120 Units of Placental Umbilical Cord Blood Transfusions in 77 Patients with Different Clinical Conditions. Abstract ; Transmedicon 2016 Bhopal O044 p 181.
72. Cappellini MD, Porter J, ElBeshlawy A, et al. Tailoring iron chelation by iron intake and serum ferritin: the prospective EPIC study of deferasirox in 1744 patients with transfusion-dependent anemias. Haematologica. 2010;95:557– 566.
73. Brittenham GM, Cohen AR, McLaren CE, Martin MB, Griffith PM, Nienhuis AW, Young NS, Allen CJ, Farrell DE, Harris JW. Hepatic iron stores and plasma ferritin concentration in patients with sickle cell anemia and thalassemia major. Am J Hematol. 1993;42:81–85. doi: 10.1002/ajh.2830420116.
74. Anderson LJ, Holden S, Davis B, Prescott E, Charrier CC, Bunce NH, Firmin DN, Wonke B, Porter J, Walker JM, Pennell DJ. Cardiovascular T2-star (T2*) magnetic resonance for the early diagnosis of myocardial iron overload. Eur Heart J. 2001; 22:2171–2179. doi: 10.1053/euhj.2001.2822.
75. St Pierre TG, Clark PR, Chuaanusorn W, Fleming AJ, Jeffrey GP, Olynyk JK, Pootrakul P, Robins E, Lindeman R. Noninvasive measurement and imaging of liver iron concentrations using proton magnetic resonance. Blood. 2005;105:855–861.doi: 10.1182/blood-2004-01-0177.
76. Thalassemia International Federation. Guidelines for the clinical management of thalassemia. 2. 2008. http://www.thalassemia.org.cy
77. Borgna-Pignatti C, Galanello R. Wintrobe's Clinical Hematology. 11. Vol. 42. Lippincott Williams & Wilkins. Philadelphia; 2004. Thalassemia and related disorders: quantitative disorders of hemoglobin synthesis; pp. 1319–1365.
78. Galanello R. Deferiprone in the treatment of transfusion-dependent thalassemia: a review and perspective. Ther Clin Risk Manag. 2003;3:795–805.
79. Cappellini MD, Cohen A, Piga A, et al. A phase 3 study of deferasirox (ICL670), a once-daily oral iron chelator, in patients with betathalassemia. Blood. 2006;107:3455– 3462.
80. Galanello R, Origa R. Once-daily oral deferasirox for the treatment of transfusional iron overload. Ex Rev of Clin Pharma. 2008;1:231–240. doi: 10.1586/17512433.1.2.231.
81. Olivieri NF, Brittenham GM. Ironchelating therapy and the treatment of thalassemia. Blood. 1997 Feb 1;89(3):739-61.
82. Brittenham, G.M., Griffith, P.M., Nienhuis, et al. (1994) Efficacy of desferrioxamine in preventing complication of iron overload in patients with thalassaemia major. New England Journal of Medicine, 331, 567–573.
83. Ridson, R. A., Flynn, D. M., and Barry, M. (1973). The relation between liver iron concentration and liver damage in transfusional iron overload in thalassaemia and the effect of chelation therapy. Gut, 14, 421.
84. Zurlo, M.G., De Stefano, P., Borgna-Pignatti, C., Di Palma, A., Piga, A., Melevendi, C., Di Gregorio, F., Burattini, M.G. & Terzoli, S. (1989) Survival and causes of death in thalassaemia major. Lancet, 8653, 27– 30.
85. Fosburg MT and Nathan DG . Treatment of Cooley’s Anemia. Blood. VOL 76, NO 3 AUGUST 1, 1990
86. Pootrakul, P., Kitcharoen, P., Yansukon, P., Wasi, P., Fucharoen, S., Charoenlarp, P., Brittenham, G, Pippard, M. & Finch, C. (1988) The effect of erythroid hyperplasia on iron balance. Blood, 71, 1124– 1129
87. Anapliotou, M.L., Kastanias, I.T., Psara, P., Evangelou, E.A., Lipakari, M. & Dimitriou, P. (1995) The contribution of hypogonadism to the development of
osteoporosis in thalassaemia major: new therapeutic approaches. Clinical Endocrinology, 42, 279 -287.
88. Weatherall DJ and Clegg JB. Inherited haemoglobin disorders: an increasing global health problem. Bull World Health Organ. 2001;79(8):704- 12. Epub 2001 Oct 24.
How to Cite
Dharmesh Chandra Sharma, Anita Arya, Purnima Kishor, Poonam Woike, Jyoti Bindal. OVERVIEW ON THALASSEMIAS: A REVIEW ARTICLE. Med. res. chronicles [Internet]. 2017Jun.30 [cited 2020Sep.24];4(03):325-37. Available from: https://medrech.com/index.php/medrech/article/view/247
Review Article