554
Views
89
CrossRef citations to date
0
Altmetric
Review

Complications of thalassemia major and their treatment

&
Pages 353-366 | Published online: 10 Jan 2014

References

  • Cao A, Galanello R. β-thalassemia. Genet. Med.12(2), 61–76 (2010).
  • Cooley TB, Lee P. A series of cases of splenomegaly in children with anemia and peculiar bone changes. Trans. Am. Pediatr.Soc.37, 29–34 (1925).
  • Ganz T, Nemeth E. Hepcidin and disorders of iron metabolism. Annu. Rev. Med.62, 347–360 (2011).
  • Esposito BP, Breuer W, Sirankapracha P, Pootrakul P, Hershko C, Cabantchik ZI. Labile plasma iron in iron overload: redox activity and susceptibility to chelation. Blood102(7), 2670–2677 (2003).
  • Borgna-Pignatti C, Cappellini MD, De Stefano P et al. Cardiac morbidity and mortality in deferoxamine- or deferiprone-treated patients with thalassemia major. Blood107(9), 3733–3737 (2006).
  • Elalfy MS, Abdin IA, El Safy UR, Ibrahim AS, Ebeid FS, Salem DS. Cardiac events and cardiac T2* in Egyptian children and young adults with β-thalassemia major taking deferoxamine. Hematol. Oncol. Stem Cell Ther.3(4), 174–178 (2010).
  • Glickstein H, El RB, Link G et al. Action of chelators in iron-loaded cardiac cells: accessibility to intracellular labile iron and functional consequences. Blood108(9), 3195–3203 (2006).
  • Bosquet J, Navarro M, Robert G, Aye P, Michel FB. Rapid desensitisation for desferrioxamine anaphylactoid reaction. Lancet8, 2(8354), 859–860 (1983).
  • Albera R, Pia F, Morra B et al. Hearing loss and desferrioxamine in homozygous β-thalassemia. Audiology27(4), 207–214 (1988).
  • Porter JB, Jaswon MS, Huehns ER, East CA, Hazell JW. Desferrioxamine ototoxicity: evaluation of risk factors in thalassaemic patients and guidelines for safe dosage. Br. J. Haematol.73(3), 403–409 (1989).
  • Arden GB, Wonke B, Kennedy C, Huehns ER. Ocular changes in patients undergoing long-term desferrioxamine treatment. Br. J. Ophthalmol.68(12), 873–877 (1984).
  • Borgna-Pignatti C, De Stefano P, Broglia AM. Visual loss in patient on high-dose subcutaneous desferrioxamine. Lancet1(8378), 681 (1984).
  • De Virgiliis S, Congia M, Frau F et al. Deferoxamine-induced growth retardation in patients with thalassemia major. J. Pediatr.113(4), 661–669 (1988).
  • Gallant T, Freedman MH, Vellend H, Francombe WH. Yersinia sepsis in patients with iron overload treated with deferoxamine. N. Engl. J. Med.314(25), 1643 (1986).
  • Cohen AR, Galanello R, Piga A, Dipalma A, Vullo C, Tricta F. Safety profile of the oral iron chelator deferiprone: a multicentre study. Br. J. Haematol.108(2), 305–312 (2000).
  • Cappellini MD, Cohen A, Piga A et al. A Phase 3 study of deferasirox (ICL670), a once-daily oral iron chelator, in patients with β-thalassemia. Blood107(9), 55–3462 (2006).
  • Piga A, Longo F, Consolati A et al. Mortality and morbidity in thalassaemia with conventional treatment. Bone Marrow Transplant.19, 1–13 (1997).
  • Ladis V, Berdousi H, Palamidou F et al. Morbidity and mortality of iron intoxication in adult patients with thalassemia major, and effectiveness of chelation. Transfus. Sci.23(3), 255–256 (2000).
  • Rund D, Rachmilewitz E. Thalassemia major 1995: older patients, new therapies. Blood Rev.9(1), 25–32 (1995).
  • Borgna-Pignatti C, Rugolotto S, De Stefano P et al. Survival and complications in patients with thalassemia major treated with transfusion and deferoxamine. Haematologica89(10), 1187–1193 (2004).
  • Marsella M, Borgna-Pignatti C, Meloni A et al. Cardiac iron and cardiac disease in males and females with transfusion-dependent thalassemia major: a T2* MRI study. Haematologica96(4), 15–20 (2011).
  • Walker JM, The heart in thalassaemia. Eur. Heart J.23(2), 102–105 (2002).
  • Anderson LJ, Holden S, Davis B et al. Cardiovascular T2-star (T2*) magnetic resonance for the early diagnosis of myocardial iron overload. Eur. Heart J.22(23), 2171–2179 (2001).
  • Kirk P, Roughton M, Porter JB et al. Cardiac T2* magnetic resonance for prediction of cardiac complications in thalassemia major. Circulation120(20), 1961–1968 (2009).
  • Pepe A, Positano V, Capra M et al. Myocardial scarring by delayed enhancement cardiovascular magnetic resonance in thalassaemia major. Heart95(20), 1688–1693 (2009).
  • Kirk P, Carpenter JP, Tanner MA, Pennell DJ. Low prevalence of fibrosis in thalassemia major assessed by late gadolinium enhancement cardiovascular magnetic resonance. J. Cardiovasc. Magn. Reson.13, 8 (2011).
  • Modell B, Khan M, Darlison M, Westwood MA, Ingram D, Pennell DJ. Improved survival of thalassaemia major in the UK and relation to T2* cardiovascular magnetic resonance. J. Cardiovasc. Magn. Reson.10, 42 (2008).
  • Pennell DJ, Porter JB, Cappellini MD et al. Continued improvement in myocardial T2* over two years of deferasirox therapy in β-thalassemia major patients with cardiac iron overload. Haematologica96(1), 48–54 (2011).
  • Wood JC, Kang BP, Thompson A et al. The effect of deferasirox on cardiac iron in thalassemia major: impact of total body iron stores. Blood116(4), 537–543 (2010).
  • Tanner MA, Galanello R, Dessi C et al. Combined chelation therapy in thalassemia major for the treatment of severe myocardial siderosis with left ventricular dysfunction. J. Cardiovasc. Magn. Reson.10, 12 (2008).
  • Lai ME, Grady RW, Vacquer S et al. Increased survival and reversion of iron-induced cardiac disease in patients with thalassemia major receiving intensive combined chelation therapy as compared to desferoxamine alone. Blood Cells Mol. Dis.45(2), 136–139 (2010).
  • Telfer PT, Warburton F, Christou S et al. Improved survival in thalassemia major patients on switching from desferrioxamine to combined chelation therapy with desferrioxamine and deferiprone. Haematologica94(12), 1777–1778 (2009).
  • Ladis V, Chouliaras G, Berdoukas V et al. Relation of chelation regimes to cardiac mortality and morbidity in patients with thalassaemia major: an observational study from a large Greek unit. Eur. J. Haematol.85(4), 335–344 (2010).
  • 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.9(5), 515–525 (2008).
  • Mirmomen S, Alavian SM, Hajarizadeh B et al. Epidemiology of hepatitis B, hepatitis C, and human immunodeficiency virus infections in patients with β-thalassemia in Iran: a multicenter study. Arch. Iran Med.9(4), 319–323 (2006).
  • Singh H, Pradhan M, Singh RL et al. High frequency of hepatitis B virus infection in patients with β-thalassemia receiving multiple transfusions. Vox Sang.84(4), 292–299 (2003).
  • Ramia S, Koussa S, Taher A et al. Hepatitis-C-virus genotypes and hepatitis-G-virus infection in Lebanese thalassaemics. Ann. Trop. Med. Parasitol.96(2), 197–202 (2002).
  • Prati D, Lin YH, De Mattei C et al. A prospective study on TT virus infection in transfusion-dependent patients with β-thalassemia. Blood93(5), 1502–1505 (1999).
  • Dodd RY. Current risk for transfusion transmitted infections. Curr. Opin. Hematol.14(6), 671–676 (2007).
  • Fraquelli M, Cassinerio E, Roghi A et al. Transient elastography in the assessment of liver fibrosis in adult thalassemia patients. Am. J. Hematol.85(8), 564–568 (2010).
  • Di Marco V, Bronte F, Cabibi D et al. Noninvasive assessment of liver fibrosis in thalassaemia major patients by transient elastography (TE): lack of interference by iron deposition. Br. J. Haematol.148(3), 476–479 (2009).
  • Angelucci E, Muretto P, Nicolucci A et al. Effects of iron overload and hepatitis C virus positivity in determining progression of liver fibrosis in thalassemia following bone marrow transplantation. Blood100(1), 17–21 (2002).
  • St Pierre TG, Clark PC, Chua-Anusorn W et al. Noninvasive measurement and imaging of liver iron concentrations using proton magnetic resonance. Blood105(2), 855–861 (2005).
  • Wood JC, Enriquez C, Ghugre N et al. MRI R2 and R2* mapping accurately estimates hepatic iron concentration in transfusion-dependent thalassemia and sickle cell disease patients. Blood106(4), 1460–1465 (2005).
  • Wood JC. Magnetic resonance imaging measurement of iron overload. Curr. Opin. Hematol.14(3), 183–190 (2007).
  • McCaughan GW, Omata M, Amarapurkar D et al. Asian Pacific Association for the Study of the Liver consensus statements on the diagnosis, management and treatment of hepatitis C virus infection. J. Gastroenterol. Hepatol.22(5), 615–633 (2007).
  • Ishak K, Baptista A, Bianchi L et al. Histological grading and staging of chronic hepatitis. J. Hepatol.22(6), 696–699 (1995).
  • Bedossa P, Poynard T. An algorithm for the grading of activity in chronic hepatitis C: the METAVIR Cooperative Study Group. Hepatology24(2), 289–293 (1996).
  • Perifanis V, Tziomalos K, Tsatra I et al. Prevalence and severity of liver disease in patients with β-thalassemia major: a single institution fifteen-year experience. Haematologica90(8), 1136–1138 (2005).
  • Borgna-Pignatti C, Vergine G, Lombardo T et al. Hepatocellular carcinoma in the thalassaemia syndromes. Br. J. Haematol.124(1), 114–117 (2004).
  • European Association for the Study of the Liver. EASL Clinical Practice Guidelines: management of chronic hepatitis B. J. Hepatol.50(2), 227–242 (2009).
  • Di Marco V, Capra M, Angelucci E et al. Italian Society for the Study of Thalassemia and Haemoglobinopathies; Italian Association for the Study of the Liver. Management of chronic viral hepatitis in patients with thalassemia: recommendations from an international panel. Blood116(16), 2875–2883 (2010).
  • Harmatz P, Jonas MM, Kwiatkowski JL et al. Safety and efficacy of pegylated interferon α-2a and ribavirin for the treatment of hepatitis C in patients with thalassemia. Haematologica93(8), 1247–1251 (2008).
  • Costin G, Kogut MD, Hyman CB, Ortega A. Endocrine abnormalities in thalassemia major. Am. J. Dis. Child.133(5), 497–502 (1979).
  • Wood JC, Noetzl L, Hyderi A, Joukar M, Coates T, Mittelman S. Predicting pituitary iron and endocrine dysfunction. Ann. NY Acad. Sci.1202, 123–128 (2010).
  • Gamberini MR, De Sanctis V, Gilli G. Hypogonadism, diabetes mellitus, hypothyroidism, hypoparathyroidism: incidence and prevalence related to iron overload and chelation therapy in patients with thalassaemia major followed from 1980 to 2007 in the Ferrara Centre. Ped. Endocrinol. Rev.6(Suppl. 1), 158–169 (2008).
  • Italian Working Group on Endocrine Complications in Non-Endocrine Disease. Multicentre study on prevalence of endocrine complications in thalassemia major. Clin. Endocrinol.42(6), 581–586 (1995).
  • Shalitin S, Carmi D, Weintrob N et al. Serum ferritin level as a predictor of impaired growth and puberty in thalassemia major patients. Eur. J. Haematol.74(2), 93–100 (2005).
  • De Sanctis V, Roos M, Gasser T et al. Impact of long-term iron chelation therapy on growth and endocrine function in thalassaemia. J. Pediatr. Endocrinol. Metab.19(4), 417–480 (2006).
  • Mowla A, Karimi M, Afrasiabi A, De Sanctis V. Prevalence of diabetes mellitus and impaired glucose tolerance in β-thalassemia patients with and without hepatitis C virus infection. Pediatr. Endocrinol. Rev.2(Suppl. 2), 282–284 (2004).
  • Cunningham MJ, Macklin EA, Neufeld EJ, Cohen AR. Complications of β-thalassemia major in North America. Blood104(1), 34–39 (2004).
  • Jensen CE, Tuck CM, Morris RW et al. Incidence of endocrine complications and clinical disease severity related to genotype analysis in patients with β-thalassemia. Eur. J. Haematol.59(2), 76–81 (1997).
  • Caruso-Nicoletti M, De Sanctis V, Cavallo L et al. Management of puberty for optimal auxological result in β-thalassaemia major. J. Pediatr. Endocrinol. Metab.14(Suppl. 2), 939–944 (2001).
  • Skordis N, Petrikkos L, Toumba M et al. Update on fertility in thalassaemia major. Pediatr. Endocrinol. Rev.2(Suppl. 2), 296–302 (2004).
  • Jensen C, Abdel-Gadir A, Cox C, Tuck SM, Wonke B. Sperm counts and quality in β-thalassaemia major. Int. J. Androl.19(6), 362–364 (1996).
  • Origa R, Piga A, Quarta G et al. Pregnancy and β-thalassemia: an Italian multicenter experience. Haematologica95(3), 376–381 (2010).
  • Zervas A, Katopodi A, Protonotariou A et al. Assessment of thyroid function in two hundred patients with β-thalassemia major. Thyroid12(2), 151–154 (2002).
  • Filosa A, Di Maio S, Aloj G, Acampora C. Longitudinal study on thyroid function in patients with thalassaemia major. J. Pediatr. Endocrinol. Metab.19(12), 1397–1404 (2006).
  • De Sanctis V, Tanas R, Gamberini MR, Sprocati M, Govoni MR, Marsella M. Exaggerated TSH response to TRH (‘sub-biochemical’ hypothyroidism) in prepubertal and adolescent thalassaemic patients with iron overload: prevalence and 20-year natural history. Ped. Endocrinol. Rev.6(Suppl. 1), 170–173 (2008).
  • Sabato AR, De Sanctis V, Atti G, Capra L, Bagni B, Vullo C. Primary hypothyroidism and low T3 syndrome in thalassemia major. Arch. Dis. Child.58(2), 120–127 (1983).
  • Farmaki K, Tzoumari I, Pappa C, Chouliaras G, Berdoukas V. Normalisation of total body iron load with very intensive combined chelation reverses cardiac and endocrine complications of thalassaemia major. Br. J. Haematol.148(3), 466–475 (2010).
  • De Sanctis V, De Sanctis E, Ricchieri P, Gubellini E, Gilli G, Gamberini MR. Mild subclinical hypothyroidism in thalassaemia major: prevalence, multigated radionuclide test, clinical and laboratory long-term follow-up study. Pediatr. Endocrinol. Rev.6(Suppl. 1), 174–180 (2008).
  • Mariotti S, Loviselli A, Murenu S et al. High prevalence of thyroid dysfunction in adult patients with β-thalassemia major submitted to amiodarone treatment. J. Endocrinol. Invest.22(1), 55–63 (1999).
  • De Sanctis V, Vullo C, Bagni B, Chiccoli L. Hypoparathyroidism in β-thalassemia major. Clinical and laboratory observations in 24 patients. Acta Haematol.88(2–3), 105–108 (1992).
  • Angelopoulos NG, Goula A, Rombopoulos G et al. Hypoparathyroidism in transfusion-dependent patients with β-thalassemia. J. Bone Miner. Metab.24(2), 138–145 (2006).
  • Karimi M, Rasekhi AR, Rasekh M, Nabavizadeh SA, Assadsangabi R, Amirhakimi GH. Hypoparathyroidism and intracerebral calcification in patients with β-thalassemia major. Eur. J. Radiol.70(3), 481–484 (2009).
  • Gamberini MR, Fortini M, De Sanctis V, Gilli G, Tetsa R. Diabetes mellitus and impaired glucose tolerance in thalassaemia major: incidence, prevalence, risk factors and survival in patients followed in the Ferrara Center. Ped. Endocrinol. Rev.2(Suppl. 2), 285–291 (2004).
  • Incorvaia C, Parmeggiani F, Mingrone G, Sebastiani A, De Sanctis V. Prevalence of retinopathy in diabetic thalassaemic patients. J. Pediatr. Endocrinol. Metab.11(Suppl. 3), 879–883 (1998).
  • Merkel PA, Simonson DC, Amiel SA et al. Insulin resistance and hyperinsulinemia in patients with thalassemia major treated by hypertransfusion. N. Engl. J. Med.318(13), 809–814 (1988).
  • Papakonstantinou O, Ladis V, Kostaridou S et al. The pancreas in β-thalassemia major: MR imaging features and correlation with iron stores and glucose disturbances. Eur. Radiol.17(6), 1535–1543 (2007).
  • Sougleri M, Labropoulou-Karatza C, Paraskevopoulou P, Fragopanagou H, Alexandrides T. Chronic hepatitis C virus infection without cirrhosis induces insulin resistance in patients with α-thalassaemia major. Eur. J. Gastroenterol. Hepatol.13(10), 1195–1199 (2001).
  • Pollack MS, Levine LS, Oberfield SE, Markenson AL. HLA-A, B, C, and DR antigen frequencies in relation to development of diabetes and variations in white cell antibody formation in highly transfused thalassemia patients. Transfusion22(4), 279–282 (1982).
  • Mangiagli A, Campisi S, De Sanctis V et al. Effects of acarbose in patients with β-thalassaemia major and abnormal glucose homeostasis. Pediatr. Endocrinol. Rev.2(Suppl. 2), 276–278 (2004).
  • Farmaki K, Angelopoulos N, Anagnostopoulos G, Gotsis E, Rombopoulos G, Tolis G. Effect of enhanced iron chelation therapy on glucose metabolism in patients with β-thalassaemia major. Br. J. Haematol.134(4), 438–444 (2006).
  • Kattamis C, Touliatos N, Haidas S, Matsaniotis N. Growth of children with thalassaemia: effect of different transfusion regimens. Arch. Dis. Child.45(242), 502–509 (1970).
  • De Sanctis V, Katz M, Vullo C, Bagni B, Ughi M, Wonke B. Effect of different treatment regimes on linear growth and final height in β-thalassaemia major. Clin. Endocrinol. (Oxf).40(6), 791–798 (1994).
  • De Sanctis V, Pinamonti A, Di Palma A et al. Growth and development in thalassaemia major patients with severe bone lesions due to desferrioxamine. Eur. J. Pediatr.155(5), 368–372 (1996).
  • Saenger P, Schwartz E, Markenson AL et al. Depressed serum somatomedin activity in β-thalassemia. J. Pediatr.96(2), 214–218 (1980).
  • Cavallo L, Gurrado R, Gallo F, Zacchino C, De Mattia D, Tatò L. Growth deficiency in polytransfused β-thalassaemia patients is not growth hormone dependent. Clin. Endocrinol.46(6), 701–706 (1997).
  • Wu KH, Tsai FJ, Peng CT. Growth hormone (GH) deficiency in patients with β-thalassemia major and the efficacy of recombinant GH treatment. Ann. Hematol.82(10), 637–640 (2003).
  • Soliman AT, Khalafallah H, Ashour R. Growth and factors affecting it in thalassemia major. Hemoglobin33(Suppl. 1), S116–S126 (2009).
  • Cavallo L, Gurrado R, Zecchino C et al. Short-term therapy with recombinant growth hormone in polytransfused thalassaemia major patients with growth deficiency. J. Pediatr. Endocrinol. Metab.11(Suppl. 3), 845–849 (1998).
  • La Rosa C, De Sanctis V, Mangiagli A et al. Growth hormone secretion in adult patients with thalassaemia. Clin. Endocrinol.62(6), 667–671 (2005).
  • Vidergor G, Goldfarb AW, Glaser B, Dresner-Pollak R. Growth hormone reserve in adult β thalassemia patients. Endocrine31(1), 33–37 (2007).
  • Poggi M, Pascucci C, Monti S et al. Prevalence of growth hormone deficiency in adult polytransfused β-thalassemia patients and correlation with transfusional and chelation parameters. J. Endocrinol. Invest.33(8), 534–538 (2010).
  • Sklar CA, Lew LQ, Yoon DJ, David R. Adrenal function in thalassemia major following long-term treatment with multiple transfusions and chelation therapy. Evidence for dissociation of cortisol and adrenal androgen secretion. Am. J. Dis. Child.141(3), 327–330 (1987).
  • Srivatsa A, Marwaha RK, Muraldharan R, Trehan A. Assessment of adrenal endocrine function in Asian thalassemics. Indian Pediatr.42(1), 31–35 (2005).
  • Scacchi M, Danesi L, Cattaneo A et al. The pituitary–adrenal axis in adult thalassaemic patients. Eur. J. Endocrinol.162(1), 43–48 (2010).
  • Bornstein SR. Predisposing factors for adrenal insufficiency. N. Engl. J. Med.360(22), 2328–2339 (2009).
  • Vogiatzi MG, Macklin EA, Trachtenberg FL et al. Differences in the prevalence of growth, endocrine and vitamin D abnormalitues among the various thalassaemia syndromes in North America. Br. J. Haematol.146(5), 546–556 (2009).
  • Origa R, Fiumana E, Gamberini MR et al. Osteoporosis in β-thalassemia: clinical and genetic aspects. Ann. NY Acad. Sci.1054, 451–456 (2005).
  • Jensen CE, Tuck SM, Agnew JE et al. High prevalence of low bone mass in thalassaemia major. Br. J. Haematol.103(4), 911–915 (1998).
  • Morabito N, Gaudio A, Lasco A et al. Osteoprotegerin and RANKL in the pathogenesis of thalassemia-induced osteoporosis: new pieces of the puzzle. J. Bone Miner Res.19(5), 722–727 (2004).
  • Voskaridou E, Christoulas D, Antoniadou L, Terpos E. Continuous increase in erythropoietic activity despite the improvement in bone mineral density by zoledronic acid in patients with thalassemia intermedia-induced osteoporosis. Acta Haematol.119(1), 40–44 (2008).
  • Holick MF. Vitamin D deficiency. N. Engl. J. Med.357(3), 266–281 (2007).
  • Jackson RD, LaCroix AZ, Gass M et al. Calcium plus vitamin D supplementation and the risk of fractures. N. Engl. J. Med.354(7), 669–683 (2006).
  • Jaipakdee S, Prasongwatana V, Premgamone A et al. The effects of potassium and magnesium supplementations on urinary risk factors of renal stone patients. J. Med. Assoc. Thai.87(3), 255–263 (2004).
  • Vieth R, Cole DE. Teriparatide, osteoporosis, calcium, and vitamin D. N. Engl. J. Med.353(6), 634–635 (2005).
  • Neuprez A, Hiligsmann M, Scholtissen S, Bruyere O, Reginster JY. Strontium ranelate: the first agent of a new therapeutic class in osteoporosis. Adv. Ther.25(12), 1235–1256 (2008).
  • Gelmi C, Borgna-Pignatti C, Franchin S, Tacchini M, Trimarchi F. Electroretinographic and visual-evoked potential abnormalities in patients with β-thalassemia major. Ophthalmologica196(1), 29–34 (1988).
  • Fabbri E, Forni GL, Guerrini G, Borgna-Pignatti C. Pseudoxanthoma-elasticum-like syndrome and thalassemia: an update. Dermatol. Online J.15(7), 7 (2009).
  • Hu X, Plomp AS, van Soest S, Wijnholds J, de Jong PT, Bergen AA. Pseudoxanthoma elasticum: a clinical, histopathological, and molecular update. Surv. Ophthalmol.48(4), 424–438 (2003).
  • Hamlin N, Beck K, Bacchelli B, Cianciulli P, Pasquali-Ronchetti I, Le Saux O. Acquired pseudoxanthoma elasticum-like syndrome in β-thalassaemia patients. Br. J. Haematol.122, 852–854 (2003).
  • Farmakis D, Deftereos S, Giakoumis A, Polymeropoulos E, Aessopos A. Rupture of chordae tendineae in patients with β-thalassemia. Eur. J. Haematol.72(4), 296–298 (2004).
  • Farmakis D, Vesleme V, Papadogianni A, Tsaftaridis P, Kapralos P, Aessopos A. Aneurysmatic dilatation of ascending aorta in a patient with β-thalassemia and a pseudoxanthoma elasticum-like syndrome. Ann. Hematol.83(9), 596–599 (2004).
  • Cianciulli P, Sorrentino F, Maffei L et al. Cardiovascular involvement in thalassaemic patients with pseudoxanthoma elasticum-like skin lesions: a long-term follow-up study. Eur. J. Clin. Invest.32(9), 700–706 (2002).
  • Li Q, Larusso J, Grand-Pierre AE, Uitto J. Magnesium carbonate-containing phosphate binder prevents connective tissue mineralization in Abcc6-/- mice-potential for treatment of pseudoxanthoma elasticum. Clin. Transl. Sci.2(6), 398–404 (2009).
  • Borgna Pignatti C, Carnelli V, Caruso V et al. Thromboembolic events in β thalassemia major: an Italian multicenter study. Acta Haematol.99(2), 76–79 (1998).
  • Taher A, Isma’eel H, Mehio G et al. Prevalence of thromboembolic events among 8,860 patients with thalassaemia major and intermedia in the Mediterranean area and Iran. Thromb. Haemost.96(4), 488–491 (2006).
  • Eldor A, Rachmilewitz EA. The hypercoagulable state in thalassemia. Blood99(1), 36–43 (2002).
  • Cappellini MD, Motta I, Musallam KM, Taher AT. Redefining thalassemia as a hypercoagulable state. Ann. NY Acad. Sci.1202, 231–236 (2010).
  • Vento S, Cainelli F, Cesario F. Infections and thalassaemia. Lancet Infect. Dis.6, 226–233 (2006).
  • Chan GC, Chan S, Ho PL, Ha SY. Effects of chelators (deferoxamine, deferiprone and deferasirox) on the growth of Klebsiella pneumoniae and Aeromonas hydrophila isolated from transfusion-dependent thalassemia patients. Hemoglobin33(5), 352–360 (2009).
  • Hansen K, Singer DB. Asplenic–hyposplenic overwhelming sepsis: postsplenectomy sepsis revisited. Pediatr. Dev. Pathol.4(2), 105–121 (2001).
  • Davies JM, Barnes R, Milligan D. Update of guidelines for the prevention and treatment of infection in patients with an absent or dysfunctional spleen. Clin. Med.2(5), 440–443 (2002).
  • Origa R, Galanello R, Perseu L et al. Cholelithiasis in thalassemia major. Eur. J. Haematol.82(1), 22–25 (2009).
  • Issaragrisil S, Piankigagum A, Wasi P. Spinal cord compression in thalassemia. Report of 12 cases and recommendations for treatment. Arch. Intern. Med.141(8), 1033–1036 (1981).
  • Cavazzana-Calvo M, Payen E, Negre O et al. Transfusion independence and HMGA2 activation after gene therapy of human β-thalassaemia. Nature467(7313), 318–322 (2010).
  • Pereira AA, Jacobson IM. New and experimental therapies for HCV. Nat. Rev. Gastroenterol. Hepatol.6(7), 403–411 (2009).
  • Angelucci E. Hematopoietic stem cell transplantation in thalassemia. Hematology Am. Soc. Hematol. Educ. Program456–462 (2010).
  • La Nasa G, Argiolu F, Giardini C et al. Unrelated bone marrow transplantation for β-thalassemia patients: the experience of the Italian Bone Marrow Transplant Group. Ann. NY Acad. Sci.1054, 186–189 (2005).
  • Cao A, Rosatelli MC, Galanello R. Control of β-thalassaemia by carrier screening, genetic counselling and prenatal diagnosis: the Sardinian experience. Ciba Found Symp.197, 137–151 (1996).

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.