Optimal management of β thalassaemia intermedia

British Journal of Haematology

Volumn 152, Issue 5, 2011, Pages 512-523

  Taher, Ali T ^a   Musallam, Khaled M ^a   Cappellini, Maria Domenica ^b   Weatherall, David J ^c  

^a AMERICAN UNIVERSITY OF BEIRUT   (Lebanon)

^b UNIVERSITY OF MILAN   (Italy)

^c UNIVERSITY OF OXFORD   (United Kingdom)

Author keywords

Fetal haemoglobin induction; Iron chelation; Splenectomy; Thalassaemia intermedia; Transfusion

Indexed keywords

4 PHENYLBUTYRIC ACID; ACETYLCYSTEINE; ACETYLSALICYLIC ACID; ALPHA GLOBIN; ALPHA TOCOPHEROL; ANTIOXIDANT; ARGINE BUTYRATE; ASCORBIC ACID; BETA GLOBIN; BUTYRIC ACID; BUTYRIC ACID DERIVATIVE; CALCIUM; CARNITINE; DEFERASIROX; DEFERIPRONE; DEFEROXAMINE; FERRITIN; HYDROXYUREA; MAGNESIUM; RECOMBINANT ERYTHROPOIETIN; SILDENAFIL; THALIDOMIDE; UNCLASSIFIED DRUG; VITAMIN D;

ALLOIMMUNIZATION; ARTHRALGIA; BETA THALASSEMIA; BLOOD TRANSFUSION; CAUSAL ATTRIBUTION; CHELATION THERAPY; DIARRHEA; DRUG EFFICACY; DRUG MEGADOSE; FERRITIN BLOOD LEVEL; GASTROINTESTINAL DISEASE; GENOTYPE; HETEROZYGOSITY; HUMAN; IRON CHELATION; NAUSEA; PATHOGENESIS; PATIENT COMPLIANCE; PHENOTYPE; PRIORITY JOURNAL; PULMONARY HYPERTENSION; REVIEW; SPLENECTOMY; TREATMENT INDICATION; TREATMENT RESPONSE; VITAMIN SUPPLEMENTATION;

BETA-THALASSEMIA; BLOOD TRANSFUSION; FETAL HEMOGLOBIN; GENOTYPE; HUMANS; IRON CHELATING AGENTS; PHENOTYPE; SPLENECTOMY;

EID: 79951553407     PISSN: 00071048     EISSN: 13652141     Source Type: Journal    
DOI: 10.1111/j.1365-2141.2010.08486.x     Document Type: Review

References (104)

1. Aessopos, A., Farmakis, D., Karagiorga, M., Voskaridou, E., Loutradi, A., Hatziliami, A., Joussef, J., Rombos, J. & Loukopoulos, D. (2001) Cardiac involvement in thalassemia intermedia: a multicenter study. Blood, 97, 3411-3416.
2. Aessopos, A., Kati, M. & Meletis, J. (2007) Thalassemia intermedia today: should patients regularly receive transfusions? Transfusion, 47, 792-800.
3. Aguilar-Lopez, L.B., Delgado-Lamas, J.L., Rubio-Jurado, B., Perea, F.J. & Ibarra, B. (2008) Thalidomide therapy in a patient with thalassemia major. Blood Cells Molecules & Diseases, 41, 136-137.
4. Amer, J. & Fibach, E. (2004) Oxidative status of platelets in normal and thalassemic blood. Thrombosis & Haemostasis, 92, 1052-1059.
5. Ataga, K.I., Cappellini, M.D. & Rachmilewitz, E.A. (2007) Beta-thalassaemia and sickle cell anaemia as paradigms of hypercoagulability. British Journal of Haematology, 139, 3-13.
6. Atichartakarn, V., Angchaisuksiri, P., Aryurachai, K., Onpun, S., Chuncharunee, S., Thakkinstian, A. & Atamasirikul, K. (2002) Relationship between hypercoagulable state and erythrocyte phosphatidylserine exposure in splenectomized haemoglobin E/beta-thalassaemic patients. British Journal of Haematology, 118, 893-898.
7. Atichartakarn, V., Angchaisuksiri, P., Aryurachai, K., Chuncharunee, S. & Thakkinstian, A. (2003a) In vivo platelet activation and hyperaggregation in hemoglobin E/beta-thalassemia: a consequence of splenectomy. International Journal of Hematology, 77, 299-303.
8. Atichartakarn, V., Likittanasombat, K., Chuncharunee, S., Chandanamattha, P., Worapongpaiboon, S., Angchaisuksiri, P. & Aryurachai, K. (2003b) Pulmonary arterial hypertension in previously splenectomized patients with beta-thalassemic disorders. International Journal of Hematology, 78, 139-145.
9. Atweh, G.F. & Loukopoulos, D. (2001) Pharmacological induction of fetal hemoglobin in sickle cell disease and beta-thalassemia. Seminars in Hematology, 38, 367-373.
10. Bennett, M., Macri, C.J. & Bathgate, S.L. (2005) Erythropoietin use in a pregnant Jehovah's witness with anemia and beta-thalassemia: a case report. Journal of Reproductive Medicine, 50, 135-137.
11. Bisharat, N., Omari, H., Lavi, I. & Raz, R. (2001) Risk of infection and death among post-splenectomy patients. Journal of Infection, 43, 182-186.
12. Bohl, D., Bosch, A., Cardona, A., Salvetti, A. & Heard, J.M. (2000) Improvement of erythropoiesis in beta-thalassemic mice by continuous erythropoietin delivery from muscle. Blood, 95, 2793-2798.
13. Borgna-Pignatti, C. (2007) Modern treatment of thalassaemia intermedia. British Journal of Haematology, 138, 291-304.
14. Cadili, A. & de Gara, C. (2008) Complications of splenectomy. American Journal of Medicine, 121, 371-375.
15. Camaschella, C., Kattamis, A.C., Petroni, D., Roetto, A., Sivera, P., Sbaiz, L., Cohen, A., Ohene-Frempong, K., Trifillis, P., Surrey, S. & Fortina, P. (1997) Different hematological phenotypes caused by the interaction of triplicated alpha-globin genes and heterozygous beta-thalassemia. American Journal of Hematology, 55, 83-88.
16. Cao, A. & Galanello, R. (2010) Beta-thalassemia. Genetics in Medicine, 12, 61-76.
17. Cappellini, M.D. (2005) Overcoming the challenge of patient compliance with iron chelation therapy. Seminars in Hematology, 42, S19-S21.
18. Cappellini, M.D., Robbiolo, L., Bottasso, B.M., Coppola, R., Fiorelli, G. & Mannucci, A.P. (2000) Venous thromboembolism and hypercoagulability in splenectomized patients with thalassaemia intermedia. British Journal of Haematology, 111, 467-473.
19. Cappellini, M.D., Cohen, A., Piga, A., Bejaoui, M., Perrotta, S., Agaoglu, L., Aydinok, Y., Kattamis, A., Kilinc, Y., Porter, J., Capra, M., Galanello, R., Fattoum, S., Drelichman, G., Magnano, C., Verissimo, M., Athanassiou-Metaxa, M., Giardina, P., Kourakli-Symeonidis, A., Janka-Schaub, G., Coates, T., Vermylen, C., Olivieri, N., Thuret, I., Opitz, H., Ressayre-Djaffer, C., Marks, P. & Alberti, D. (2006) A phase 3 study of deferasirox (ICL670), a once-daily oral iron chelator, in patients with beta-thalassemia. Blood, 107, 3455-3462.
20. Cario, H., Wegener, M., Debatin, K.M. & Kohne, E. (2002) Treatment with hydroxyurea in thalassemia intermedia with paravertebral pseudotumors of extramedullary hematopoiesis. Annals of Hematology, 81, 478-482.
21. Cossu, P., Toccafondi, C., Vardeu, F., Sanna, G., Frau, F., Lobrano, R., Cornacchia, G., Nucaro, A., Bertolino, F., Loi, A., De Virgiliis, S. & Cao, A. (1981) Iron overload and desferrioxamine chelation therapy in beta-thalassemia intermedia. European Journal of Pediatrics, 137, 267-271.
22. Derchi, G., Forni, G.L., Formisano, F., Cappellini, M.D., Galanello, R., D'Ascola, G., Bina, P., Magnano, C. & Lamagna, M. (2005) Efficacy and safety of sildenafil in the treatment of severe pulmonary hypertension in patients with hemoglobinopathies. Haematologica, 90, 452-458.
23. Dixit, A., Chatterjee, T.C., Mishra, P., Choudhry, D.R., Mahapatra, M., Tyagi, S., Kabra, M., Saxena, R. & Choudhry, V.P. (2005) Hydroxyurea in thalassemia intermedia--a promising therapy. Annals of Hematology, 84, 441-446.
24. Domenica Cappellini, M., Graziadei, G., Ciceri, L., Comino, A., Bianchi, P., Porcella, A. & Fiorelli, G. (2000) Oral isobutyramide therapy in patients with thalassemia intermedia: results of a phase II open study. Blood Cells Molecules & Diseases, 26, 105-111.
25. Dover, G.J. (1998) Hemoglobin switching protocols in thalassemia. Experience with sodium phenylbutyrate and hydroxyurea. Annals of the New York Academy of Sciences, 850, 80-86.
26. de Franceschi, L., Turrini, F., Honczarenko, M., Ayi, K., Rivera, A., Fleming, M.D., Law, T., Mannu, F., Kuypers, F.A., Bast, A., van der Vijgh, W.J. & Brugnara, C. (2004) In vivo reduction of erythrocyte oxidant stress in a murine model of beta-thalassemia. Haematologica, 89, 1287-1298.
27. Galanello, R. & Cao, A. (1998) Relationship between genotype and phenotype. Thalassemia intermedia. Annals of the New York Academy of Sciences, 850, 325-333.
28. Galanello, R., Sanna, S., Perseu, L., Sollaino, M.C., Satta, S., Lai, M.E., Barella, S., Uda, M., Usala, G., Abecasis, G.R. & Cao, A. (2009) Amelioration of Sardinian beta0 thalassemia by genetic modifiers. Blood, 114, 3935-3937.
29. Gell, D., Kong, Y., Eaton, S.A., Weiss, M.J. & Mackay, J.P. (2002) Biophysical characterization of the alpha-globin binding protein alpha-hemoglobin stabilizing protein. Journal of Biological Chemistry, 277, 40602-40609.
30. Haidar, R., Mhaidli, H. & Taher, A.T. (2010) Paraspinal extramedullary hematopoiesis in patients with thalassemia intermedia. European Spine Journal, 19, 871-878.
31. Hmida, S., Mojaat, N., Maamar, M., Bejaoui, M., Mediouni, M. & Boukef, K. (1994) Red cell alloantibodies in patients with haemoglobinopathies. Nouvelle Revue Française d'Hématologie, 36, 363-366.
32. Hoppe, C., Vichinsky, E., Lewis, B., Foote, D. & Styles, L. (1999) Hydroxyurea and sodium phenylbutyrate therapy in thalassemia intermedia. American Journal of Hematology, 62, 221-227.
33. Karimi, M., Darzi, H. & Yavarian, M. (2005) Hematologic and clinical responses of thalassemia intermedia patients to hydroxyurea during 6years of therapy in Iran. Journal of Pediatric Hematology & Oncology, 27, 380-385.
34. Karimi, M., Mohammadi, F., Behmanesh, F., Samani, S.M., Borzouee, M., Amoozgar, H. & Haghpanah, S. (2010) Effect of combination therapy of hydroxyurea with l-carnitine and magnesium chloride on hematologic parameters and cardiac function of patients with beta-thalassemia intermedia. European Journal of Haematology, 84, 52-58.
35. Kihm, A.J., Kong, Y., Hong, W., Russell, J.E., Rouda, S., Adachi, K., Simon, M.C., Blobel, G.A. & Weiss, M.J. (2002) An abundant erythroid protein that stabilizes free alpha-haemoglobin. Nature, 417, 758-763.
36. * MR for cardiac and liver iron assessment among five thalassemia centers. Journal of Magnetic Resonance Imaging, 32, 315-319.
37. Littera, R., La Nasa, G., Derchi, G., Cappellini, M.D., Chang, C.Y. & Contu, L. (2002) Long-term treatment with sildenafil in a thalassemic patient with pulmonary hypertension. Blood, 100, 1516-1517.
38. Loukopoulos, D., Voskaridou, E., Stamoulakatou, A., Papassotiriou, Y., Kalotychou, V., Loutradi, A., Cozma, G., Tsiarta, H. & Pavlides, N. (1998) Hydroxyurea therapy in thalassemia. Annals of the New York Academy of Sciences, 850, 120-128.
39. Mancuso, A., Maggio, A., Renda, D., Di Marzo, R. & Rigano, P. (2006) Treatment with hydroxycarbamide for intermedia thalassaemia: decrease of efficacy in some patients during long-term follow up. British Journal of Haematology, 133, 103-108.
40. Masera, N., Tavecchia, L., Capra, M., Cazzaniga, G., Vimercati, C., Pozzi, L., Biondi, A. & Masera, G. (2010) Optimal response to thalidomide in a patient with thalassaemia major resistant to conventional therapy. Blood Transfusion, 8, 63-65.
41. McLaughlin, V.V., Archer, S.L., Badesch, D.B., Barst, R.J., Farber, H.W., Lindner, J.R., Mathier, M.A., McGoon, M.D., Park, M.H., Rosenson, R.S., Rubin, L.J., Tapson, V.F., Varga, J., Harrington, R.A., Anderson, J.L., Bates, E.R., Bridges, C.R., Eisenberg, M.J., Ferrari, V.A., Grines, C.L., Hlatky, M.A., Jacobs, A.K., Kaul, S., Lichtenberg, R.C., Lindner, J.R., Moliterno, D.J., Mukherjee, D., Pohost, G.M., Rosenson, R.S., Schofield, R.S., Shubrooks, S.J., Stein, J.H., Tracy, C.M., Weitz, H.H. & Wesley, D.J.;.A.C.C.F/.A.H.A. (2009) ACCF/AHA 2009 expert consensus document on pulmonary hypertension: a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents and the American Heart Association: developed in collaboration with the American College of Chest Physicians, American Thoracic Society, Inc., and the Pulmonary Hypertension Association. Circulation, 119, 2250-2294.
42. Menzel, S., Garner, C., Gut, I., Matsuda, F., Yamaguchi, M., Heath, S., Foglio, M., Zelenika, D., Boland, A., Rooks, H., Best, S., Spector, T.D., Farrall, M., Lathrop, M. & Thein, S.L. (2007) A QTL influencing F cell production maps to a gene encoding a zinc-finger protein on chromosome 2p15. Nature Genetics, 39, 1197-1199.
43. + cells. Journal of Clinical Investigation, 118, 248-258.
44. Napoli, N., Carmina, E., Bucchieri, S., Sferrazza, C., Rini, G.B. & Di Fede, G. (2006) Low serum levels of 25-hydroxy vitamin D in adults affected by thalassemia major or intermedia. Bone, 38, 888-892.
45. Nassar, A.H., Usta, I.M. & Taher, A.M. (2006) Beta-thalassemia intermedia and pregnancy: should we anticoagulate? Journal of Thrombosis & Haemostasis, 4, 1413-1414.
46. Nassar, A.H., Naja, M., Cesaretti, C., Eprassi, B., Cappellini, M.D. & Taher, A. (2008) Pregnancy outcome in patients with beta-thalassemia intermedia at two tertiary care centers, in Beirut and Milan. Haematologica, 93, 1586-1587.
47. Nuinoon, M., Makarasara, W., Mushiroda, T., Setianingsih, I., Wahidiyat, P.A., Sripichai, O., Kumasaka, N., Takahashi, A., Svasti, S., Munkongdee, T., Mahasirimongkol, S., Peerapittayamongkol, C., Viprakasit, V., Kamatani, N., Winichagoon, P., Kubo, M., Nakamura, Y. & Fucharoen, S. (2010) A genome-wide association identified the common genetic variants influence disease severity in beta0-thalassemia/hemoglobin E. Human Genetics, 127, 303-314.
48. O'Donnell, A., Premawardhena, A., Arambepola, M., Allen, S.J., Peto, T.E., Fisher, C.A., Rees, D.C., Olivieri, N.F. & Weatherall, D.J. (2007) Age-related changes in adaptation to severe anemia in childhood in developing countries. Proceedings of the National Academy of Sciences USA, 104, 9440-9444.
49. Olivieri, N.F. (1999) The beta-thalassemias. New England Journal of Medicine, 341, 99-109.
50. Olivieri, N.F., Koren, G., Matsui, D., Liu, P.P., Blendis, L., Cameron, R., McClelland, R.A. & Templeton, D.M. (1992) Reduction of tissue iron stores and normalization of serum ferritin during treatment with the oral iron chelator L1 in thalassemia intermedia. Blood, 79, 2741-2748.
51. Olivieri, N.F., Muraca, G.M., O'Donnell, A., Premawardhena, A., Fisher, C. & Weatherall, D.J. (2008) Studies in haemoglobin E beta-thalassaemia. British Journal of Haematology, 141, 388-397.
52. Pace, B.S., Shartava, A., Pack-Mabien, A., Mulekar, M., Ardia, A. & Goodman, S.R. (2003) Effects of N-acetylcysteine on dense cell formation in sickle cell disease. American Journal of Hematology, 73, 26-32.
53. Panigrahi, I., Dixit, A., Arora, S., Kabra, M., Mahapatra, M., Choudhry, V.P. & Saxena, R. (2005) Do alpha deletions influence hydroxyurea response in thalassemia intermedia? Hematology, 10, 61-63.
54. Perrine, S.P., Ginder, G.D., Faller, D.V., Dover, G.H., Ikuta, T., Witkowska, H.E., Cai, S.P., Vichinsky, E.P. & Olivieri, N.F. (1993) A short-term trial of butyrate to stimulate fetal-globin-gene expression in the beta-globin disorders. New England Journal of Medicine, 328, 81-86.
55. Pfeifer, W.P., Degasperi, G.R., Almeida, M.T., Vercesi, A.E., Costa, F.F. & Saad, S.T. (2008) Vitamin E supplementation reduces oxidative stress in beta thalassaemia intermedia. Acta Haematologica, 120, 225-231.
56. Pierre, B., Maillot, F., Casset-Sedon, D., Regina, S., Sitbon, O. & Cosnay, P. (2006) Chronic pulmonary thromboembolism revealing beta-thalassemia intermedia after splenectomy. La Revue de Medecine Interne, 27, 950-953.
57. Pippard, M.J. & Weatherall, D.J. (1988) Iron balance and the management of iron overload in beta-thalassemia intermedia. Birth Defects Original Article Series, 23, 29-33.
58. Pippard, M.J., Callender, S.T., Warner, G.T. & Weatherall, D.J. (1979) Iron absorption and loading in beta-thalassaemia intermedia. Lancet, 2, 819-821.
59. Pootrakul, P., Sirankapracha, P., Sankote, J., Kachintorn, U., Maungsub, W., Sriphen, K., Thakernpol, K., Atisuk, K., Fucharoen, S., Chantraluksri, U., Shalev, O. & Hoffbrand, A.V. (2003) Clinical trial of deferiprone iron chelation therapy in beta-thalassaemia/haemoglobin E patients in Thailand. British Journal of Haematology, 122, 305-310.
60. Porter, J., Galanello, R., Saglio, G., Neufeld, E.J., Vichinsky, E., Cappellini, M.D., Olivieri, N., Piga, A., Cunningham, M.J., Soulieres, D., Gattermann, N., Tchernia, G., Maertens, J., Giardina, P., Kwiatkowski, J., Quarta, G., Jeng, M., Forni, G.L., Stadler, M., Cario, H., Debusscher, L., Della Porta, M., Cazzola, M., Greenberg, P., Alimena, G., Rabault, B., Gathmann, I., Ford, J.M., Alberti, D. & Rose, C. (2008) Relative response of patients with myelodysplastic syndromes and other transfusion-dependent anaemias to deferasirox (ICL670): a 1-yr prospective study. European Journal of Haematology, 80, 168-176.
61. Premawardhena, A., Fisher, C.A., Olivieri, N.F., de Silva, S., Sloane-Stanley, J., Wood, W.G. & Weatherall, D.J. (2005) A novel molecular basis for beta thalassemia intermedia poses new questions about its pathophysiology. Blood, 106, 3251-3255.
62. Restivo Pantalone, G., Renda, D., Valenza, F., D'Amato, F., Vitrano, A., Cassara, F., Rigano, P., Di Salvo, V., Giangreco, A., Bevacqua, E. & Maggio, A. (2010) Hepatocellular carcinoma in patients with thalassaemia syndromes: clinical characteristics and outcome in a long term single centre experience. British Journal of Haematology, 150, 245-247.
63. * study. Annals of Hematology, 89, 585-589.
64. Sampietro, M., Cazzola, M., Cappellini, M.D. & Fiorelli, G. (1983) The triplicated alpha-gene locus and heterozygous beta thalassaemia: a case of thalassaemia intermedia. British Journal of Haematology, 55, 709-710.
65. Sankaran, V.G., Menne, T.F., Xu, J., Akie, T.E., Lettre, G., Van Handel, B., Mikkola, H.K., Hirschhorn, J.N., Cantor, A.B. & Orkin, S.H. (2008) Human fetal hemoglobin expression is regulated by the developmental stage-specific repressor BCL11A. Science, 322, 1839-1842.
66. Sankaran, V.G., Xu, J., Ragoczy, T., Ippolito, G.C., Walkley, C.R., Maika, S.D., Fujiwara, Y., Ito, M., Groudine, M., Bender, M.A., Tucker, P.W. & Orkin, S.H. (2009) Developmental and species-divergent globin switching are driven by BCL11A. Nature, 460, 1093-1097.
67. Saxon, B.R., Rees, D. & Olivieri, N.F. (1998) Regression of extramedullary haemopoiesis and augmentation of fetal haemoglobin concentration during hydroxyurea therapy in beta thalassaemia. British Journal of Haematology, 101, 416-419.
68. Singer, S.T., Kuypers, F.A., Olivieri, N.F., Weatherall, D.J., Mignacca, R., Coates, T.D., Davies, S., Sweeters, N. & Vichinsky, E.P. (2005) Fetal haemoglobin augmentation in E/beta(0) thalassaemia: clinical and haematological outcome. British Journal of Haematology, 131, 378-388.
69. Spanos, T., Karageorga, M., Ladis, V., Peristeri, J., Hatziliami, A. & Kattamis, C. (1990) Red cell alloantibodies in patients with thalassemia. Vox Sanguinis, 58, 50-55.
70. St Pierre, T.G., Clark, P.R., Chua-anusorn, W., Fleming, A.J., Jeffrey, G.P., Olynyk, J.K., Pootrakul, P., Robins, E. & Lindeman, R. (2005) Noninvasive measurement and imaging of liver iron concentrations using proton magnetic resonance. Blood, 105, 855-861.
71. Steinberg, M.H., Forget, B.G., Higgs, D.R. & Weatherall, D.J. (2009) Disorders of Hemoglobin: Genetics Pathophysiology, and Clinical Management, 2nd edn. Cambridge University Press, Cambridge.
72. Sturgeon, P., Itano, H.A. & Bergren, W.R. (1955) Genetic and biochemical studies of intermediate types of Cooley's anaemia. British Journal of Haematology, 1, 264-277.
73. Taher, A., Abou-Mourad, Y., Abchee, A., Zalouaa, P. & Shamseddine, A. (2002) Pulmonary thromboembolism in beta-thalassemia intermedia: are we aware of this complication? Hemoglobin, 26, 107-112.
74. Taher, A., Isma'eel, H. & Cappellini, M.D. (2006a) Thalassemia intermedia: revisited. Blood Cells Molecules & Diseases, 37, 12-20.
75. Taher, A., Isma'eel, H., Mehio, G., Bignamini, D., Kattamis, A., Rachmilewitz, E.A. & Cappellini, M.D. (2006b) Prevalence of thromboembolic events among 8, 860 patients with thalassaemia major and intermedia in the Mediterranean area and Iran. Thrombosis & Haemostasis, 96, 488-491.
76. Taher, A., El Rassi, F., Isma'eel, H., Koussa, S., Inati, A. & Cappellini, M.D. (2008a) Correlation of liver iron concentration determined by R2 magnetic resonance imaging with serum ferritin in patients with thalassemia intermedia. Haematologica, 93, 1584-1586.
77. Taher, A., Otrock, Z.K., Uthman, I. & Cappellini, M.D. (2008b) Thalassemia and hypercoagulability. Blood Reviews, 22, 283-292.
78. Taher, A., Hershko, C. & Cappellini, M.D. (2009a) Iron overload in thalassaemia intermedia: reassessment of iron chelation strategies. British Journal of Haematology, 147, 634-640.
79. Taher, A., Musallam, K.M., El Rassi, F., Duca, L., Inati, A., Koussa, S. & Cappellini, M.D. (2009b) Levels of non-transferrin-bound iron as an index of iron overload in patients with thalassaemia intermedia. British Journal of Haematology, 146, 569-572.
80. Taher, A., Porter, J.B., Kattamis, A., Viprakasit, V., Lawniczek, T., Pereno, R., Schoenborn-Kellenberger, O. & Cappellini, M.D. (2009c) Randomized phase II study evaluating the efficacy and safety of deferasirox in non-transfusion-dependent thalassemia patients with iron overload [abstract]. Blood, 114, 5111.
81. Taher, A.T., Musallam, K.M. & Inati, A. (2009d) The hypercoagulable state in thalassemia intermedia. Hemoglobin, 33(Suppl. 1), S160-S169.
82. Taher, A.T., Musallam, K.M. & Inati, A. (2009e) Iron overload: consequences, assessment, and monitoring. Hemoglobin, 33(Suppl. 1), S46-S57.
83. Taher, A.T., Musallam, K.M., El-Beshlawy, A., Karimi, M., Daar, S., Belhoul, K., Saned, M.S., Graziadei, G. & Cappellini, M.D. (2010a) Age-related complications in treatment-naive patients with thalassaemia intermedia. British Journal of Haematology, 150, 486-489.
84. Taher, A.T., Musallam, K.M., Karimi, M., El-Beshlawy, A., Belhoul, K., Daar, S., Saned, M., Cesaretti, C. & Cappellini, M.D. (2010b) Splenectomy and thrombosis: the case of thalassemia intermedia. Journal of Thrombosis & Haemostasis, 8, 2152-2158.
85. Taher, A.T., Musallam, K.M., Karimi, M., El-Beshlawy, A., Belhoul, K., Daar, S., Saned, M.S., El-Chafic, A.H., Fasulo, M.R. & Cappellini, M.D. (2010c) Overview on practices in thalassemia intermedia management aiming for lowering complication rates across a region of endemicity: the OPTIMAL CARE study. Blood, 115, 1886-1892.
86. Taher, A.T., Musallam, K.M., Nasreddine, W., Hourani, R., Inati, A. & Beydoun, A. (2010d) Asymptomatic brain magnetic resonance imaging abnormalities in splenectomized adults with thalassemia intermedia. Journal of Thrombosis & Haemostasis, 8, 54-59.
87. Taher, A.T., Musallam, K.M., Wood, J.C. & Cappellini, M.D. (2010e) Magnetic resonance evaluation of hepatic and myocardial iron deposition in transfusion-independent thalassemia intermedia compared to regularly transfused thalassemia major patients. American Journal of Hematology, 85, 288-290.
88. Tavazzi, D., Duca, L., Graziadei, G., Comino, A., Fiorelli, G. & Cappellini, M.D. (2001) Membrane-bound iron contributes to oxidative damage of beta-thalassaemia intermedia erythrocytes. British Journal of Haematology, 112, 48-50.
89. Tesoriere, L., D'Arpa, D., Butera, D., Allegra, M., Renda, D., Maggio, A., Bongiorno, A. & Livrea, M.A. (2001) Oral supplements of vitamin E improve measures of oxidative stress in plasma and reduce oxidative damage to LDL and erythrocytes in beta-thalassemia intermedia patients. Free Radical Research, 34, 529-540.
90. Tesoriere, L., Allegra, M., Butera, D., Gentile, C. & Livrea, M.A. (2006) Cytoprotective effects of the antioxidant phytochemical indicaxanthin in beta-thalassemia red blood cells. Free Radical Research, 40, 753-761.
91. Thein, S.L., Wainscoat, J.S., Sampietro, M., Old, J.M., Cappellini, D., Fiorelli, G., Modell, B. & Weatherall, D.J. (1987) Association of thalassaemia intermedia with a beta-globin gene haplotype. British Journal of Haematology, 65, 367-373.
92. Treadwell, M.J. & Weissman, L. (2001) Improving adherence with deferoxamine regimens for patients receiving chronic transfusion therapy. Seminars in Hematology, 38, 77-84.
93. Uda, M., Galanello, R., Sanna, S., Lettre, G., Sankaran, V.G., Chen, W., Usala, G., Busonero, F., Maschio, A., Albai, G., Piras, M.G., Sestu, N., Lai, S., Dei, M., Mulas, A., Crisponi, L., Naitza, S., Asunis, I., Deiana, M., Nagaraja, R., Perseu, L., Satta, S., Cipollina, M.D., Sollaino, C., Moi, P., Hirschhorn, J.N., Orkin, S.H., Abecasis, G.R., Schlessinger, D. & Cao, A. (2008) Genome-wide association study shows BCL11A associated with persistent fetal hemoglobin and amelioration of the phenotype of beta-thalassemia. Proceedings of the National Academy of Sciences USA, 105, 1620-1625.
94. Vichinsky, E., Onyekwere, O., Porter, J., Swerdlow, P., Eckman, J., Lane, P., Files, B., Hassell, K., Kelly, P., Wilson, F., Bernaudin, F., Forni, G.L., Okpala, I., Ressayre-Djaffer, C., Alberti, D., Holland, J., Marks, P., Fung, E., Fischer, R., Mueller, B.U. & Coates, T. (2007) A randomised comparison of deferasirox versus deferoxamine for the treatment of transfusional iron overload in sickle cell disease. British Journal of Haematology, 136, 501-508.
95. Voskaridou, E., Douskou, M., Terpos, E., Papassotiriou, I., Stamoulakatou, A., Ourailidis, A., Loutradi, A. & Loukopoulos, D. (2004) Magnetic resonance imaging in the evaluation of iron overload in patients with beta thalassaemia and sickle cell disease. British Journal of Haematology, 126, 736-742.
96. Voskaridou, E., Christoulas, D., Antoniadou, L. & Terpos, E. (2008a) Continuous increase in erythropoietic activity despite the improvement in bone mineral density by zoledronic acid in patients with thalassemia intermedia-induced osteoporosis. Acta Haematologica, 119, 40-44.
97. Voskaridou, E., Christoulas, D., Konstantinidou, M., Tsiftsakis, E., Alexakos, P. & Terpos, E. (2008b) Continuous improvement of bone mineral density two years post zoledronic acid discontinuation in patients with thalassemia-induced osteoporosis: long-term follow-up of a randomized, placebo-controlled trial. Haematologica, 93, 1588-1590.
98. Voskaridou, E., Plata, E., Douskou, M., Papadakis, M., Delaki, E.E., Christoulas, D. & Terpos, E. (2010) Treatment with deferasirox (Exjade) effectively decreases iron burden in patients with thalassaemia intermedia: results of a pilot study. British Journal of Haematology, 148, 332-334.
99. Wahlberg, K., Jiang, J., Rooks, H., Jawaid, K., Matsuda, F., Yamaguchi, M., Lathrop, M., Thein, S.L. & Best, S. (2009) The HBS1L-MYB intergenic interval associated with elevated HbF levels shows characteristics of a distal regulatory region in erythroid cells. Blood, 114, 1254-1262.
100. Weatherall, D.J. (2001) Phenotype-genotype relationships in monogenic disease: lessons from the thalassaemias. Nature Reviews Genetics, 2, 245-255.
101. Weatherall, D. (2004) 2003 William Allan Award address. The Thalassemias: the role of molecular genetics in an evolving global health problem. American Journal of Human Genetics, 74, 385-392.
102. Weatherall, D.J. & Clegg, J.B. (2001) The Thalassaemia Syndromes, 4th edn. Blackwell Science, Oxford.
103. Weinberg, R.S., Ji, X., Sutton, M., Perrine, S., Galperin, Y., Li, Q., Liebhaber, S.A., Stamatoyannopoulos, G. & Atweh, G.F. (2005) Butyrate increases the efficiency of translation of gamma-globin mRNA. Blood, 105, 1807-1809.
104. * mapping accurately estimates hepatic iron concentration in transfusion-dependent thalassemia and sickle cell disease patients. Blood, 106, 1460-1465.