Thalassaemia major

J. Savulescu, Thalassaemia Major The Murky Story of Deferiprone, ... 

Iron absorption may also be increased secondary to chronic haemolysis as in patients with thalassaemia intermedia. In this group of patients, the anaemia is not usually sufficiently severe to necessitate regular blood transfusions as in thalassaemia major, but iron accumulates over many years from increased absorption via the gut. However, unlike haemochromatosis, venesection is not a therapeutic option, and iron chelation is the only effective way to remove the excess iron. 

Patients with transfusion siderosis require a long-term programme of chelation therapy. In patients who are transfusion-dependent from infancy (thalassaemia major, congenital refractory anaemia) chelation therapy is commenced after 10-20 transfusions at about 3 years of age. In older patients with acquired transfusion-dependent anaemias chelation is commenced after 20 transfusions or when the serum ferritin is 2-3 times the upper limit of normal. 

A 26-year-old subject with beta-thalassaemia major had been transfused 404 imits of blood over his lifetime. His iron stores were so high (estimated at above 100 g) that he triggered a metal detector at an airport security checkpoint (Jim RTS 1979 Lancet 2 1028). 

Barratt PS, Toogood IR. Hearing loss attributed to desferrioxamine in patients with beta-thalassaemia major. Med J Aust 1987 147(4) 177-9. 

NaseUi A, Vignolo M, Di Battista E, Garzia P, Forni GL, Traverse T, Aicardi G. Long-term follow-up of skeletal dysplasia in thalassaemia major. J Pediatr Endocrinol Metab 1998 ll(Suppl 3) 817-25. 

Chan YL, Pang LM, Chik KW, Cheng JC, Li CK. Patterns of bone diseases in transfusion-dependent homozygous thalassaemia major predominance of osteoporosis and desferrioxamine-induced bone dysplasia. Pediatr Radiol 2002 32(7) 492-7. 

Chiu RWK, Lau TK, Leung TN, Chow KCK, Chui DKH, Lo YMD. Prenatal exclusion of beta-thalassaemia major by examination of maternal plasma. Lancet 2002 360 998-1000. 

Balocco M, Carrara P, Pinto V, Forni GL. Daily alternating deferasirox and deferi-prone therapy for hard-to-chelate P-thalassaemia major patients. Am J Hematol 2010 85 460-1. 

Al-Refaie FN, Wickens DG, Wonke B, Kontoghiorghes GJ, Hoffbrand AV (1992) Serum non-transferrin-bound iron in beta-thalassaemia major patients treated with desferrioxamine and LI. Br J Haematol 82 431-436 Alfrey AC, Froment DH, Hammond WS (1989) Role of iron in the tubulo-interstitial injury in nephrotoxic serum nephritis. Kidney Int 36 753-759... 

Modell B, Letsky EA, Flynn DM, Peto R, Weatherall DJ (1982) Survival and desferrioxamine in thalassaemia major. Br Med J 284 1081-1084 Motekaitis RJ, Martell AE (1991) Stabilities of the iron(III) chelates of 1,2-diemethyl-3-hydroxy-4-pyridinone and related ligands. Inorg Chim Acta 183 71-80... 

Theil EC, Aisen P (1987) The storage and transport of iron in animal cells. In Winkelmann G, van der Helm G, Neilands JB (eds) Iron transport in microbes, plants and animals. VCH, Weinheim, pp 491-520 Tondury P, Kontoghiorghes GJ, Ridolfi-Luthy A, Hirt A, Hoffbrand AV, Lottenbach AM, Sonderegger T, Wagner HP (1990) LI (l,2-dimethyl-3-hydroxypyrid-4-one) for oral iron chelation in patients with beta-thalassaemia major. Br J Haematol 76 550-553... 

Thio D, Prasad V, Anslow P, Lennox P. Marrow proliferation as a cause of hearing loss in beta-thalassaemia major. J Laryngol Otol 2008 122(11) 1253-6. 

Thalassaemia major presents in early childhood with hepa-tosplenomegaly, anaemia and jaundice. Thalassaemia minor... 

In July 2013, the American Heart Association released a consensus statement regarding cardiovascular function and treatment in beta-thalassaemia major [8 ]. The paper states that serum ferritin and liver iron concentration are not adequate surrogates for cardiac iron measurement indeed, two articles published in 2013 discuss differences in organ... 

A duodenal perforation in a 6.5-year-old male child with thalassaemia major was reported [31 ]. He received 625 mg deferasirox daily since the age of 3, and was not on any other medication. After treatment, he resumed chelation therapy together with omeprazole to prevent peptic ulcer. One study indicated no link between lactose intolerance and the incidence of G1 adverse effects in beta-thalassaemia patients treated with deferasirox [32 ]. 

A retrospective multicentre randomised open-label long-term sequential deferiprone-deferoxamine trial on patients with thalassaemia major showed enhanced left ventricular ejection fraction [41 ]. 

Savulescu J. Thalassaemia major the murky story of deferiprone. BMJ February 14,2004 328(7436) 358-9. 

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