Highlights & Basics
- There are at least four different and distinct alpha-thalassemias: silent carrier (1 affected alpha-globin gene), alpha-thalassemia trait (2 affected alpha-globin genes), hemoglobin H (Hb H) disease (typically 3 affected alpha-globin genes), and alpha-thalassemia major (also known as Hb Bart hydrops fetalis syndrome; typically deletion of all 4 alpha-globin genes).
- The severity of the clinical manifestations of anemia and hemolysis correspond with the genetic defect and the degree of impairment in alpha-globin synthesis.
- Alpha-thalassemia is found in malarial regions of the world (sub-Saharan Africa, the Mediterranean basin, the Middle East, South Asia, and Southeast Asia) and should be suspected in patients with these ethnic backgrounds and with microcytosis and/or anemia.
- The vast majority of alpha-thalassemia patients are clinically well and most are asymptomatic. Many patients with Hb H are also clinically well, but are at risk for acute hemolytic episodes, aplastic crises, iron overload (even in the absence of chronic transfusions), hypersplenism, and endocrine disease.
- Education is an important part of management and should cover the risks of acute events and, in genetic counseling, the risks of conceiving a child with Hb H disease or the potentially devastating alpha-thalassemia major.
Quick Reference
History & Exam
Key Factors
Other Factors
Diagnostics Tests
Treatment Options
Definition
Epidemiology
Etiology
Pathophysiology
Images
Citations
Northern California Comprehensive Thalassemia Center. Standards of care guidelines for thalassemia. 2012 [internet publication].[Full Text]
Thalassaemia International Federation. 2021 guidelines for the management of transfusion dependent thalassaemia (TDT). 4th ed. Version 2.01. 2021 [internet publication].[Full Text]
Thalassaemia International Federation. Guidelines for the management of non transfusion dependent thalassaemia (NTDT). 2nd edition. 2017 [internet publication].[Full Text]
Northern California Comprehensive Thalassemia Center. Standards of care guidelines for thalassemia. 2012 [internet publication].[Full Text]
1. Weatherall D. The molecular basis for phenotypic variability of the common thalassaemias. Mol Med Today. 1995 Apr;1(1):15-20.[Abstract]
2. Ribeiro DM, Sonati MF. Regulation of human alpha-globin gene expression and alpha-thalassemia. Genet Mol Res. 2008 Oct 14;7(4):1045-53.[Abstract][Full Text]
3. Vichinsky E. Complexity of alpha thalassemia: growing health problem with new approaches to screening, diagnosis, and therapy. Ann N Y Acad Sci. 2010 Aug;1202:180-7.[Abstract]
4. Harteveld CL, Higgs DR. Alpha-thalassemia. Orphanet J Rare Dis. 2010 May 28;5:13.[Abstract][Full Text]
5. Chen FE, Ooi C, Ha SY, et al. Genetic and clinical features of hemoglobin H disease in Chinese patients. N Engl J Med. 2000 Aug 24;343(8):544-50.[Abstract][Full Text]
6. Pootrakul P, Winichagoon P, Fucharoen S, et al. Homozygous haemoglobin Constant Spring: a need for revision of concept. Hum Genet. 1981;59(3):250-5.[Abstract]
7. Henderson S, Chapple M, Rugless M, et al. Haemoglobin H hydrops fetalis syndrome associated with homozygosity for the alpha2-globin gene polyadenylation signal mutation AATAAA-->AATA--. Br J Haematol. 2006 Dec;135(5):743-5.[Abstract][Full Text]
8. Vichinsky EP, MacKlin EA, Waye JS, et al. Changes in the epidemiology of thalassemia in North America: a new minority disease. Pediatrics. 2005 Dec;116(6):e818-25.[Abstract]
9. Lorey F, Cunningham G, Vichinsky EP, et al. Universal newborn screening for Hb H disease in California. Genet Test. 2001 Summer;5(2):93-100.[Abstract]
10. Chan V, Chan VW, Tang M, et al. Molecular defects in Hb H hydrops fetalis. Br J Haematol. 1997 Feb;96(2):224-8.[Abstract][Full Text]
11. Chui DH, Waye JS. Hydrops fetalis caused by alpha-thalassemia: an emerging health care problem. Blood. 1998 Apr 1;91(7):2213-22.[Abstract][Full Text]
12. Gibbons RJ, Brueton L, Buckle VJ, et al. Clinical and hematologic aspects of the X-linked alpha-thalassemia/mental retardation syndrome (ATR-X). Am J Med Genet. 1995 Jan 30;55(3):288-99.[Abstract]
13. Alli NA. Acquired haemoglobin H disease. Hematology. 2005 Oct;10(5):413-8.[Abstract][Full Text]
14. Boehme WM, Piira TA, Kurnick JE, et al. Acquired hemoglobin H in refractor sideroblastic anemia: a preleukemic marker. Arch Intern Med. 1978 Apr;138(4):603-6.[Abstract]
15. Steensma DP, Gibbons RJ, Higgs DR. Acquired alpha-thalassemia in association with myelodysplastic syndrome and other hematologic malignancies. Blood. 2005 Jan 15;105(2):443-52.[Abstract][Full Text]
16. Thalassaemia International Federation. Guidelines for the management of alpha-thalassaemia. 2023.
17. Modell B, Darlison M. Global epidemiology of haemoglobin disorders and derived service indicators. Bull World Health Organ. 2008 Jun;86(6):480-7.[Abstract][Full Text]
18. Flint J, Hill AV, Bowden DK, et al. High frequencies of alpha-thalassaemia are the result of natural selection by malaria. Nature. 1986 Jun 19-25;321(6072):744-50.[Abstract]
19. Association of Public Health Laboratories; Centers for Disease Control and Prevention. Hemoglobinopathies: current practices for screening, confirmation and follow-up. Dec 2015 [internet publication].[Full Text]
20. Weatherall DJ. The definition and epidemiology of non-transfusion-dependent thalassemia. Blood Rev. 2012 Apr;26(suppl 1):S3-6.[Abstract]
21. Kattamis A, Kwiatkowski JL, Aydinok Y. Thalassaemia. Lancet. 2022 Jun 18;399(10343):2310-24.[Abstract]
22. Jomoui W, Fucharoen G, Sanchaisuriya K, et al. Hemoglobin Constant Spring among Southeast Asian populations: haplotypic heterogeneities and phylogenetic analysis. PLoS One. 2015;10(12):e0145230.[Abstract][Full Text]
23. Beutler E, West C. Hematologic differences between African-Americans and whites: the roles of iron deficiency and alpha-thalassemia on hemoglobin levels and mean corpuscular volume. Blood. 2005 Jul 15;106(2):740-5.[Abstract][Full Text]
24. Liebhaber SA, Cash FE, Ballas SK. Human alpha-globin gene expression: the dominant role of the alpha 2-locus in mRNA and protein synthesis. J Biol Chem. 1986 Nov 15;261(32):15327-33.[Abstract][Full Text]
25. Benesch RE, Ranney HM, Benesch R, et al. The chemistry of the Bohr effect: II. Some properties of hemoglobin H. J Biol Chem. 1961 Nov;236(11):2926-9.[Abstract][Full Text]
26. Rigas DA, Koler RD. Decreased erythrocyte survival in hemoglobin H disease as a result of the abnormal properties of hemoglobin H: the benefit of splenectomy. Blood. 1961 Jul;18(1):1-17.[Abstract][Full Text]
27. Gabuzda TG, Nathan DG, Gardner FH. The metabolism of the individual C14-labeled hemoglobins in patients with H-thalassemia, with observations on radiochromate binding to the hemoglobins during red cell survival. J Clin Invest. 1965 Feb;44(2):315-25.[Abstract][Full Text]
28. Pootrakul P, Sirankapracha P, Hemsorach S, et al. A correlation of erythrokinetics, ineffective erythropoiesis, and erythroid precursor apoptosis in Thai patients with thalassemia. Blood. 2000 Oct 1;96(7):2606-12.[Abstract]
29. Schrier SL, Rachmilewitz E, Mohandas N. Cellular and membrane properties of alpha and beta thalassemic erythrocytes are different: implication for differences in clinical manifestations. Blood. 1989 Nov 1;74(6):2194-202.[Abstract][Full Text]
30. Schrier SL, Bunyaratvej A, Khuhapinant A, et al. The unusual pathobiology of Hemoglobin Constant Spring red blood cells. Blood. 1997 Mar 1;89(5):1762-9.[Abstract][Full Text]
31. Rachmilewitz EA, Peisach J, Bradley TB, et al. Role of haemichromes in the formation of inclusion bodies in haemoglobin H disease. Nature. 1969 Apr 19;222(5190):248-50.[Abstract]
32. Waugh SM, Low PS. Hemichrome binding to band 3: nucleation of Heinz bodies on the erythrocyte membrane. Biochemistry. 1985 Jan 1;24(1):34-9.[Abstract]
33. Kuypers FA, Yuan J, Lewis RA, et al. Membrane phospholipid asymmetry in human thalassemia. Blood. 1998 Apr 15;91(8):3044-51.[Abstract][Full Text]
34. Mensah C, Sheth S. Optimal strategies for carrier screening and prenatal diagnosis of alpha-and beta-thalassemia. Hematology Am Soc Hematol Educ Program. 2021 Dec 10;2021(1):607-13.[Abstract][Full Text]
35. Bender MA, Yusuf C, Davis T, et al. Newborn screening practices and alpha-thalassemia detection - United States, 2016. MMWR Morb Mortal Wkly Rep. 2020 Sep 11;69(36):1269-72.[Abstract][Full Text]
36. ACOG Committee on Obstetrics. ACOG practice bulletin no. 78: hemoglobinopathies in pregnancy. Obstet Gynecol. 2007 Jan;109(1):229-37.[Abstract]
37. MacKenzie TC, Amid A, Angastiniotis M, et al. Consensus statement for the perinatal management of patients with alpha thalassemia major. Blood Adv. 2021 Dec 28;5(24):5636-9.[Abstract][Full Text]
38. Thalassemia.com. Genetics of thalassemia: genetic counseling. 2023 [internet publication].[Full Text]
39. National Health Service (UK). Screening for sickle cell and thalassaemia. Oct 2022 [internet publication].[Full Text]
40. American College of Obstetricians and Gynecologists. Practice advisory: hemoglobinopathies in pregnancy. Aug 2022 [internet publication].[Full Text]
41. American College of Obstetricians and Gynecologists. Committee opinion no. 690: carrier screening in the age of genomic medicine. Mar 2017 [internet publication].[Full Text]
42. American College of Obstetricians and Gynecologists. Committee opinion no. 691: carrier screening for genetic conditions. Mar 2017 [internet publication].[Full Text]
43. Chui DH, Fucharoen S, Chan V. Hemoglobin H disease: not necessarily a benign disorder. Blood. 2003 Feb 1;101(3):791-800.[Abstract][Full Text]
44. Wiromrat P, Rattanathongkom A, Laoaroon N, et al. Bone mineral density and Dickkopf-1 in adolescents with non-deletional hemoglobin H disease. J Clin Densitom. 2023 Apr 26;101379.[Abstract]
45. Laosombat V, Viprakasit V, Chotsampancharoen T, et al. Clinical features and molecular analysis in Thai patients with HbH disease. Ann Hematol. 2009 Dec;88(12):1185-92.[Abstract]
46. Wu JH, Shih LY, Kuo TT, et al. Intrathoracic extramedullary hematopoietic tumor in hemoglobin H disease. Am J Hematol. 1992 Dec;41(4):285-8.[Abstract]
47. Benz EJ Jr, Wu CC, Sohani AR. Case records of the Massachusetts General Hospital. Case 25-2011. A 62-year-old woman with anemia and paraspinal masses. N Engl J Med. 2011 Aug 18;365(7):648-58.[Abstract]
48. Thalassaemia International Federation. A short guide for the management of transfusion-dependent thalassaemia. 2nd ed. 2022 [internet publication].[Full Text]
49. Sabath DE. Molecular diagnosis of thalassemias and hemoglobinopathies: an ACLPS critical review. Am J Clin Pathol. 2017 Jul 1;148(1):6-15.[Abstract][Full Text]
50. Northern California Comprehensive Thalassemia Center. Standards of care guidelines for thalassemia. 2012 [internet publication].[Full Text]
51. Wood JC. Diagnosis and management of transfusion iron overload: the role of imaging. Am J Hematol. 2007 Dec;82(suppl 12):1132-5.[Abstract][Full Text]
52. Lal A, Goldrich ML, Haines DA, et al. Heterogeneity of hemoglobin H disease in childhood. N Engl J Med. 2011 Feb 24;364(8):710-8.[Abstract][Full Text]
53. Yin XL, Zhang XH, Zhou TH, et al. Hemoglobin H disease in Guangxi province, Southern China: clinical review of 357 patients. Acta Haematol. 2010;124(2):86-91.[Abstract]
54. Fucharoen G, Trithipsombat J, Sirithawee S, et al. Molecular and hematological profiles of hemoglobin EE disease with different forms of alpha-thalassemia. Ann Hematol. 2006 Jul;85(7):450-4.[Abstract]
55. Carmel R. Pernicious anemia: the expected findings of very low serum cobalamin levels, anemia, and macrocytosis are often lacking. Arch Intern Med. 1988 Aug;148(8):1712-4.[Abstract]
56. Healton EB, Savage DG, Brust JC, et al. Neurologic aspects of cobalamin deficiency. Medicine (Baltimore). 1991 Jul;70(4):229-45.[Abstract]
57. Li X, Zhou Q, Zhang M, et al. Sonographic markers of fetal alpha-thalassemia major. J Ultrasound Med. 2015 Feb;34(2):197-206.[Abstract]
58. Norton ME, Chauhan SP, Dashe JS; Society for Maternal-Fetal Medicine. Society for maternal-fetal medicine (SMFM) clinical guideline #7: nonimmune hydrops fetalis. Am J Obstet Gynecol. 2015 Feb;212(2):127-39.[Abstract][Full Text]
59. Harn-A-Morn P, Wanapirak C, Sirichotiyakul S, et al. Effectiveness of ultrasound algorithm in prenatal diagnosis of hemoglobin Bart's disease among pregnancies at risk. Int J Gynaecol Obstet. 2022 Nov;159(2):451-6.[Abstract]
60. Hudecova I, Chiu RW. Non-invasive prenatal diagnosis of thalassemias using maternal plasma cell free DNA. Best Pract Res Clin Obstet Gynaecol. 2017 Feb;39:63-73.[Abstract]
61. Yang X, Ye Y, Fan D, et al. Non‑invasive prenatal diagnosis of thalassemia through multiplex PCR, target capture and next‑generation sequencing. Mol Med Rep. 2020 Aug;22(2):1547-57.[Abstract][Full Text]
62. Thalassaemia International Federation. 2021 guidelines for the management of transfusion dependent thalassaemia (TDT). 4th ed. Version 2.01. 2021 [internet publication].[Full Text]
63. Traeger-Synodinos J, Harteveld CL, Old JM, et al. EMQN best practice guidelines for molecular and haematology methods for carrier identification and prenatal diagnosis of the haemoglobinopathies. Eur J Hum Genet. 2015 Apr;23(4):426-37.[Abstract][Full Text]
64. Ruangvutilert P, Phatihattakorn C, Yaiyiam C, et al. Pregnancy outcomes among women affected with thalassemia traits. Arch Gynecol Obstet. 2023 Feb;307(2):431-8.[Abstract][Full Text]
65. Akhavan-Niaki H, Youssefi Kamangari R, Banihashemi A, et al. Hematologic features of alpha thalassemia carriers. Int J Mol Cell Med. 2012 Summer;1(3):162-7.[Abstract][Full Text]
66. Vichinsky EP. Clinical manifestations of alpha-thalassemia. Cold Spring Harb Perspect Med. 2013 May 1;3(5):a011742.[Abstract][Full Text]
67. Vogiatzi MG, Macklin EA, Fung EB, et al. Bone disease in thalassemia: a frequent and still unresolved problem. J Bone Miner Res. 2009 Mar;24(3):543-57.[Abstract][Full Text]
68. Beutler E. G6PD deficiency. Blood. 1994 Dec 1;84(11):3613-36.[Abstract][Full Text]
69. Hsu HC, Lin CK, Tsay SH, et al. Iron overload in Chinese patients with hemoglobin H disease. Am J Hematol. 1990 Aug;34(4):287-90.[Abstract]
70. Tso SC, Loh TT, Chen WW, et al. Iron overload in thalassaemic patients in Hong Kong. Ann Acad Med Singapore. 1984 Jul;13(3):487-90.[Abstract]
71. Kattamis A, Papassotiriou I, Palaiologou D, et al. The effects of erythropoetic activity and iron burden on hepcidin expression in patients with thalassemia major. Haematologica. 2006 Jun;91(6):809-12.[Abstract]
72. Lin CK, Lin JS, Jiang ML. Iron absorption is increased in hemoglobin H diseases. Am J Hematol. 1992 May;40(1):74-5.[Abstract]
73. Thalassaemia International Federation. Guidelines for the management of non transfusion dependent thalassaemia (NTDT). 2nd edition. 2017 [internet publication].[Full Text]
74. Musallam KM, Cappellini MD, Taher AT. Evaluation of the 5mg/g liver iron concentration threshold and its association with morbidity in patients with beta-thalassemia intermedia. Blood Cells Mol Dis. 2013 Jun;51(1):35-8.[Abstract]
75. Xia S, Zhang W, Huang L, et al. Comparative efficacy and safety of deferoxamine, deferiprone and deferasirox on severe thalassemia: a meta-analysis of 16 randomized controlled trials. PLoS One. 2013 Dec 23;8(12):e82662.[Abstract][Full Text]
76. Taher AT, Porter J, Viprakasit V, et al. Deferasirox reduces iron overload significantly in nontransfusion-dependent thalassemia: 1-year results from a prospective, randomized, double-blind, placebo-controlled study. Blood. 2012 Aug 2;120(5):970-7.[Abstract][Full Text]
77. Taher AT, Porter JB, Viprakasit V, et al. Deferasirox effectively reduces iron overload in non-transfusion-dependent thalassemia (NTDT) patients: 1-year extension results from the THALASSA study. Ann Hematol. 2013 Nov;92(11):1485-93.[Abstract][Full Text]
78. US Food and Drug Administration. Exjade (deferasirox): boxed warning. Oct 2013 [internet publication].[Full Text]
79. Vichinsky E. Clinical application of deferasirox: practical patient management. Am J Hematol. 2008 May;83(5):398-402.[Abstract][Full Text]
80. Maggio A, Kattamis A, Felisi M, et al. Evaluation of the efficacy and safety of deferiprone compared with deferasirox in paediatric patients with transfusion-dependent haemoglobinopathies (DEEP-2): a multicentre, randomised, open-label, non-inferiority, phase 3 trial. Lancet Haematol. 2020 Jun;7(6):e469-78.[Abstract]
81. Kittipoom T, Tantiworawit A, Punnachet T, et al. The long-term efficacy of deferiprone in thalassemia patients with iron overload: real-world data from the Registry Database. Hemoglobin. 2022 Mar;46(2):75-80.[Abstract]
82. Tricta F, Uetrecht J, Galanello R, et al. Deferiprone-induced agranulocytosis: 20 years of clinical observations. Am J Hematol. 2016 Oct;91(10):1026-31.[Abstract][Full Text]
83. Cappellini MD, Cohen A, Piga A, et al. A phase 3 study of deferasirox (ICL670), a once-daily oral iron chelator, in patients with beta-thalassemia. Blood. 2006 May 1;107(9):3455-62.[Abstract][Full Text]
84. Anderson LJ, Westwood MA, Holden S, et al. Myocardial iron clearance during reversal of siderotic cardiomyopathy with intravenous desferrioxamine: a prospective study using T2* cardiovascular magnetic resonance. Br J Haematol. 2004 Nov;127(3):348-55.[Abstract]
85. Schrier S. New treatment options for thalassemia. Clin Adv Hematol Oncol. 2004 Dec;2(12):783-4.[Abstract]
86. Kopterides P, Tsangaris I, Orfanos S. Do not forget pulmonary hypertension in asplenic patients. Am J Med. 2008 Nov;121(11):e21.[Abstract]
87. Phrommintikul A, Sukonthasarn A, Kanjanavanit R, et al. Splenectomy: a strong risk factor for pulmonary hypertension in patients with thalassaemia. Heart. 2006 Oct;92(10):1467-72.[Abstract]
88. Cohen AR, Galanello R, Pennell DJ, et al. Thalassemia. Hematology Am Soc Hematol Educ Program. 2004(1):14-34.[Abstract][Full Text]
89. Centers for Disease Control and Prevention. Vaccine recommendations and guidelines of the ACIP. Altered immunocompetence: general best practice guidelines for immunization. Aug 2023 [internet publication].[Full Text]
90. Singer ST, Wu V, Mignacca R, et al. Alloimmunization and erythrocyte autoimmunization in transfusion-dependent thalassemia patients of predominantly Asian descent. Blood. 2000 Nov 15;96(10):3369-73.[Abstract][Full Text]
91. Cogliandro T, Derchi G, Mancuso L, et al; Society for the Study of Thalassemia and Hemoglobinopathies (SoSTE). Guideline recommendations for heart complications in thalassemia major. J Cardiovasc Med (Hagerstown). 2008 May;9(5):515-25.[Abstract]
92. Geneen LJ, Dorée C, Estcourt LJ. Interventions for improving adherence to iron chelation therapy in people with sickle cell disease or thalassaemia. Cochrane Database Syst Rev. 2023 Mar 6;(3):CD012349.[Abstract][Full Text]
93. Locke M, Reddy PS, Badawy SM. Adherence to iron chelation therapy among adults with thalassemia: a systematic review. Hemoglobin. 2022 Jul;46(4):201-13.[Abstract]
94. Reddy PS, Locke M, Badawy SM. A systematic review of adherence to iron chelation therapy among children and adolescents with thalassemia. Ann Med. 2022 Dec;54(1):326-42.[Abstract][Full Text]
95. Baronciani D, Angelucci E, Potschger U, et al. Hemopoietic stem cell transplantation in thalassemia: a report from the European Society for Blood and Bone Marrow Transplantation Hemoglobinopathy Registry, 2000-2010. Bone Marrow Transplant. 2016 Apr;51(4):536-41.[Abstract]
96. Li C, Mathews V, Kim S, et al. Related and unrelated donor transplantation for beta-thalassemia major: results of an international survey. Blood Adv. 2019 Sep 10;3(17):2562-70.[Abstract][Full Text]
97. Schwab ME, Lianoglou BR, Gano D, et al. The impact of in utero transfusions on perinatal outcomes in patients with alpha thalassemia major: the UCSF registry. Blood Adv. 2023 Jan 24;7(2):269-79.[Abstract][Full Text]
98. Kreger EM, Singer ST, Witt RG, et al. Favorable outcomes after in utero transfusion in fetuses with alpha thalassemia major: a case series and review of the literature. Prenat Diagn. 2016 Dec;36(13):1242-9.[Abstract]
99. Hui PW, Pang P, Tang MHY. 20 years review of antenatal diagnosis of haemoglobin Bart's disease and treatment with intrauterine transfusion. Prenat Diagn. 2022 Aug;42(9):1155-61.[Abstract]
100. Lorey F, Charoenkwan P, Witkowska HE, et al. Hb H hydrops foetalis syndrome: a case report and review of literature. Br J Haematol. 2001 Oct;115(1):72-8.[Abstract][Full Text]
101. Henderson S, Pitman M, McCarthy J, et al. Molecular prenatal diagnosis of Hb H hydrops fetalis caused by haemoglobin Adana and the implications to antenatal screening for alpha-thalassaemia. Prenat Diagn. 2008 Sep;28(9):859-61.[Abstract]
102. Liang ST, Wong VC, So WW, et al. Homozygous alpha-thalassaemia: clinical presentation, diagnosis and management: a review of 46 cases. Br J Obstet Gynaecol. 1985 Jul;92(7):680-4.[Abstract]
103. Brown KE, Young NS. Parvovirus B19 infection and hematopoiesis. Blood Rev. 1995 Sep;9(3):176-82.[Abstract]
104. Thalassaemia International Federation. Nutrition in thalassaemia and pyruvate kinase deficiency: a guideline for clinicians. 2023.
105. Taher A, Porter J, Viprakasit V, et al. Estimation of liver iron concentration by serum ferritin measurement in non-transfusion-dependent thalassemia patients: analysis from the 1-year THALASSA study. Paper presented at: 17th Congress of the European Hematology Association. Jun 14-17, 2012. Amsterdam, The Netherlands. Abstract 0927. Haematologica. 2012 Jul;97(suppl_1):383.[Full Text]
106. Price VE, Dutta S, Blanchette VS, et al. The prevention and treatment of bacterial infections in children with asplenia or hyposplenia: practice considerations at the Hospital for Sick Children, Toronto. Pediatr Blood Cancer. 2006 May 1;46(5):597-603.[Abstract]
107. Tuck SM. Fertility and pregnancy in thalassemia major. Ann N Y Acad Sci. 2005 Nov;1054(1):300-7.[Abstract]
108. Locatelli F, Thompson AA, Kwiatkowski JL, et al. Betibeglogene autotemcel gene therapy for non-beta(0)/beta(0) genotype beta-thalassemia. N Engl J Med. 2022 Feb 3;386(5):415-27.[Abstract][Full Text]
109. ClinicalTrials.gov. In utero hematopoietic stem cell transplantation for alpha-thalassemia major (ATM). NCT02986698. May 2023 [internet publication].[Full Text]
110. Kuo KHM, Layton DM, Lal A, et al. Safety and efficacy of mitapivat, an oral pyruvate kinase activator, in adults with non-transfusion dependent alpha-thalassaemia or beta-thalassaemia: an open-label, multicentre, phase 2 study. Lancet. 2022 Aug 13;400(10351):493-501.[Abstract]
111. ClinicalTrials.gov. A study of etavopivat in patients with thalassemia or sickle cell disease. NCT04987489. Apr 2023 [internet publication].[Full Text]
112. Cappellini MD, Viprakasit V, Taher AT, et al; BELIEVE Investigators. A phase 3 trial of luspatercept in patients with transfusion-dependent beta-thalassemia. N Engl J Med. 2020 Mar 26;382(13):1219-31.[Abstract][Full Text]
113. Taher AT, Cappellini MD, Kattamis A, et al; BEYOND Investigators. Luspatercept for the treatment of anaemia in non-transfusion-dependent beta-thalassaemia (BEYOND): a phase 2, randomised, double-blind, multicentre, placebo-controlled trial. Lancet Haematol. 2022 Oct;9(10):e733-44.[Abstract]
114. Thalassemia Foundation of Canada. Guidelines for the clinical care of patients with thalassemia in Canada. 2016 [internet publication].[Full Text]
115. Klein HG, Spahn DR, Carson JL. Red blood cell transfusion in clinical practice. Lancet. 2007 Aug 4;370(9585):415-26.[Abstract]
116. Cunningham MJ, Macklin EA, Neufeld EJ, et al; Thalassemia Clinical Research Network. Complications of beta-thalassemia major in North America. Blood. 2004 Jul 1;104(1):34-9.[Abstract][Full Text]
117. Alavian SM, Tabatabaei SV. Treatment of chronic hepatitis C in polytransfused thalassaemic patients: a meta-analysis. J Viral Hepat. 2010 Apr;17(4):236-44.[Abstract]
118. Ngim CF, Lai NM, Hong JY, et al. Growth hormone therapy for people with thalassaemia. Cochrane Database Syst Rev. 2020 May 28;(5):CD012284.[Abstract][Full Text]
119. Arcasoy A, Ocal G, Kemahli S, et al. Recombinant human growth hormone treatment in children with thalassemia major. Pediatr Int. 1999 Dec;41(6):655-61.[Abstract]
120. Northern California Comprehensive Thalassemia Center. Standards of care guidelines for thalassemia. 2012 [internet publication].[Full Text]
