Iron overload and toxicity: The hidden risk of multiple blood transfusions

Vox Sanguinis

Volumn 97, Issue 3, 2009, Pages 185-197

  Shander, A ^a   Cappellini, M D ^b   Goodnough, L T ^c  

^a ENGLEWOOD HOSPITAL AND MEDICAL CENTER   (United States)

^b UNIVERSITY OF MILAN   (Italy)

^c STANFORD UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Chelation therapy; Iron metabolism; Iron overload; Iron toxicity; Transfusion

Indexed keywords

DEFERASIROX; DEFERIPRONE; DEFEROXAMINE; DEFEROXAMINE MESYLATE; FERRITIN; IRON; TRANSFERRIN;

AGRANULOCYTOSIS; ANEMIA; ARTHRALGIA; BLEEDING; BLOOD DISEASE; BLOOD TRANSFUSION; CLINICAL FEATURE; CLINICAL TRIAL; COMPUTER ASSISTED TOMOGRAPHY; DATA BASE; DIAGNOSTIC TEST; DRUG APPROVAL; DRUG BLOOD LEVEL; DRUG EFFICACY; DRUG ERUPTION; DRUG EXCRETION; DRUG HALF LIFE; DRUG SAFETY; DRUG TOLERABILITY; EAR DISEASE; ERYTHROPOIESIS; EYE TOXICITY; GASTROINTESTINAL SYMPTOM; GENE MUTATION; HEMOCHROMATOSIS; HUMAN; IRON ABSORPTION; IRON CHELATION; IRON METABOLISM; IRON OVERLOAD; IRON STORAGE; IRON TRANSPORT; LABORATORY TEST; MORBIDITY; MORTALITY; MUSCULOSKELETAL DISEASE; NEUROTOXICITY; NUCLEAR MAGNETIC RESONANCE IMAGING; PATHOPHYSIOLOGY; PHLEBOTOMY; PRIORITY JOURNAL; REVIEW; RISK ASSESSMENT; ZINC DEFICIENCY;

ANEMIA; BLOOD TRANSFUSION; CARDIOMYOPATHIES; CERULOPLASMIN; CHELATION THERAPY; CHRONIC DISEASE; HEMOCHROMATOSIS; HUMANS; IRON; IRON CHELATING AGENTS; IRON OVERLOAD; LIVER DISEASES; PHLEBOTOMY; RISK; TRANSFERRIN;

EID: 70349545970     PISSN: 00429007     EISSN: 14230410     Source Type: Journal    
DOI: 10.1111/j.1423-0410.2009.01207.x     Document Type: Review

References (104)

1. Langlois d'Estaintot B, Santambrogio P, Granier T, Gallois B, Chevalier JM, Précigoux G, Levi S, Arosio P : Crystal structure and biochemical properties of the human mitochondrial ferritin and its mutant Ser144Ala. J Mol Biol 2004 340 : 277 293
2. Andrews NC : Disorders of iron metabolism. N Engl J Med 1999 341 : 1986 1995
3. Porter J : Pathophysiology of iron overload. Hematol Oncol Clin 2005 19 (Suppl. 1 7 12
4. Vichinsky E : Consensus document for transfusion-related iron overload. Semin Hematol 2001 38 (Suppl. 1 2 4 (Pubitemid 32110266)
5. Morrison ED, Brandhagen DJ, Phatak PD, Barton JC, Krawitt EL, El-Serag HG, Gordon SC, Galan MV, Tung BY, Ioannou GN, Kowdley KV : Serum ferritin level predicts advanced hepatic fibrosis among U.S. patients with phenotypic hemochromatosis. Ann Intern Med 2003 138 : 627 633
6. Crichton RR, Ward RJ : An overview of iron metabolism: molecular and cellular criteria for the selection of iron chelators. Curr Med Chem 2003 10 : 997 1004
7. Porter JB : Practical management of iron overload. Br J Haematol 2001 115 : 239 252
8. National Heart, Lung, and Blood Institute : The Management of Sickle Cell Disease, 4th edn. Bethesda, Maryland, National Institutes of Health, 2002 : NIH publication 02-2117
9. Files B, Brambilla D, Kutlar A, Miller S, Vichinsky E, Wang W, Granger S, Adams RJ : Longitudinal changes in ferritin during chronic transfusion: a report from the Stroke Prevention Trial in Sickle Cell Anemia (STOP). J Pediatr Hematol Oncol 2002 24 : 244 245
10. Olivieri NF, Brittenham GM : Iron-chelating therapy and the treatment of thalassemia. Blood 1997 89 : 739 761
11. Olivieri NF, Nathan DG, MacMillan JH, Wayne AS, Liu PP, McGee A, Martin M, Koren G, Cohen AR : Survival in medically treated patients with homozygous β-thalassemia. N Engl J Med 1994 331 : 574 578
12. Darbari DS, Kple-Faget P, Kwagyan J, Rana S, Gordeuk VR, Castro O : Circumstances of death in adult sickle cell disease patients. Am J Hematol 2006 81 : 858 863
13. Khuri FR : Weighing the hazards of erythropoiesis stimulation in patients with cancer. N Engl J Med 2007 356 : 2445 2448
14. Oates PS : The role of hepcidin and ferroportin in iron absorption. Histol Histopathol 2007 22 : 791 804
15. Sharp P, Srai SK : Molecular mechanisms involved in intestinal iron absorption. World J Gastroenterol 2007 13 : 2716 2724
16. Ganz T : Molecular control of iron transport. J Am Soc Nephrol 2007 18 : 394 400
17. Andrews NC : Forging a field: the golden age of iron biology. Blood 2008 112 : 219 230
18. Goodnough LT, Weis G : Anemia of chronic disease. N Engl J Med 2005 352 : 43 55
19. Lee DA, Goodfellow JM : The pH-induced release of iron from transferrin investigated with a continuum electrostatic model. Biophys J 1998 74 : 2747 2759
20. Aguilar-Martinez P : Non-HFE-related hereditary iron overload. Presse Med 2007 36 : 1279 1291
21. Lebrón JA, Bennett MJ, Vaughn DE, Chirino AJ, Snow PM, Mintler GA, Feder JN, Bjorkman PJ : Crystal structure of the hemochromatosis protein HFE and characterization of its interaction with transferrin receptor. Cell 1998 93 : 111 123
22. Pietrangelo A : Hereditary hemochromatosis - a new look at an old disease. N Engl J Med 2004 350 : 2383 2397
23. Ponka P : Rare causes of hereditary iron overload. Semin Hematol 2002 39 : 249 262
24. Wrighting DM, Andrews NC : Iron homeostasis and erythropoiesis. Curr Topics Dev Biol 2008 82 : 141 167
25. Miyajima H : Genetic disorders affecting proteins of iron and copper metabolism: clinical implications. Intern Med 2002 41 : 762 769
26. Malcovati L : Impact of transfusion dependency and secondary iron overload on the survival of patients with myelodysplastic syndromes. Leuk Res 2007 31 (Suppl. 3 S2 S6
27. Goodnough LT, Bravo J, Hsueh Y, Keating L, Brittenham GM : Red blood cell volume in autologous and homologous blood units. implications for risk/benefit assessment for autologous blood 'crossover' and directed blood transfusion. Transfusion 1989 29 : 821 822
28. Smiley D, Dagogo-Jack S, Umpierrez G : Therapy insight: metabolic and endocrine disorders in sickle cell disease. Nat Clin Pract Endocrinol Metab 2008 4 : 102 109
29. Marwah SS, Blann A, Harrison P, Lumley MA, Wright J, McDowell J, Phillips JD, Rea C, Bareford D : Increased non-transferrin bound iron in plasma-depleted SAG-M red blood cell units. Vox Sang 2002 82 : 122 126
30. Grosse R, Lund U, Caruso V, Fischer R, Janka GE, Magnano C, Engelhardt R, Dürken M, Lielsen P : Non-transferrin-bound iron during blood transfusion cycles in beta-thalassemia major. Ann N Y Acad Sci 2005 1054 : 429 432
31. Kohgo Y, Ikuta K, Ohtake T, Torimoto Y, Kato J : Body iron metabolism and pathophysiology of iron overload. Int J Hematol 2008 88 : 7 15
32. Ballas SK : Iron overload is a determinant of morbidity and mortality in adult patients with sickle cell disease. Semin Hematol 2001 38 (Suppl. 1 30 36
33. Piga A, Longo F, Duca L, Roggero S, Vinciguerra T, Calabrese R, Hershko C, Cappellini MD : High nontransferrin bound iron levels and heart disease in thalassemia major. Am J Hematol 2008 84 : 29 33
34. Sanz G, Nomdedeu B, Such E, Bernal T, Belkaid M, Ardanaz MT, Marco V, Pedro C, Ramos F, del Cañizo MC, Luño E, Cobo F, Carbonell F, Gomez V, Muñoz JA, Amigo ML, Bailen A, Bonadad S, Tormo M, Andreu R, Arrizabalaga B, Arilla MJ, Bueno J, Requena MJ, Bargay J, Sanchez J, Senent L, Arenillas L, de Paz R, Xicoy B, Duarte R, Cervera J : Independent impact of iron overload and transfusion dependency on survival and leukemic evolution in patients with myelodysplastic syndrome. Presented at the Annual Meeting of the American Society of Hematology. December 6-9, 2008; San Francisco, California. Abstract 640
35. Hershko C, Peto TE : Non-transferrin plasma iron. Br J Haematol 1987 66 : 149 151
36. Siah CW, Ombiga J, Adams LA, Trinder D, Olynyk JK : Normal iron metabolism and the pathophysiology of overload disorders. Clin Biochem Rev 2006 27 : 5 16
37. Wang WC, Ahmed N, Hanna M : Non-transferrin-bound iron in long-term transfusion in children with congenital anemias. J Pediatr 1986 108 : 552 557
38. Conte D, Piperno A, Mandelli C, Fargion S, Cesana M, Brunelli L, Ferrario L, Velio P, Zaramella MG, Tribelli C : Clinical, biochemical and histological features of primary haemochromatosis: a report of 67 cases. Liver 1986 6 : 310 315
39. Schwartz KA, Li Z, Schwartz DE, Cooper TG, Braselton WE. Earliest cardiac toxicity induced by iron overload selectively inhibits electrical conduction. J Appl Physiol 2002 93 : 746 751
40. Oudit GY, Trivieri MG, Khaper N, Liu PP, Backx PH : Role of L-type Ca2+ channels in iron transport and iron-overload cardiomyopathy. J Mol Med 2006 84 : 349 364
41. Borgna-Pignatti C, Rugolotto S, De Stefano P, Zhao H, Cappellini MD, Del Vecchio GC, Romeo MA, Forni GL, Gamberini MR, Ghilardi R, Piga A, Cnaan A : Survival and complications in patients with thalassemia major treated with transfusion and deferoxamine. Haematologica 2004 89 : 1187 1193
42. Cazzola M, Malcovati L : Myelodysplastic syndromes - coping with ineffective hematopoiesis. N Engl J Med 2005 352 : 536 538
43. Malcovati L, Della Porta MG, Cazzola M : Predicting survival and leukemic evolution in patients with myelodysplastic syndrome. Haematologica 2006 91 : 1588 1590
44. Garcia-Manero G, Shan J, Faderl S, Cortes J, Ravandi F, Borthakur G, Wierda WG, Pierce S, Estey E, Liu J, Huang X, Kantarjian H : A prognostic score for patients with lower risk myelodysplastic syndrome. Leukemia 2008 22 : 538 543
45. Armand P, Kim HT, Cutler CS, Ho VT, Koreth J, Alyea EP, Soiffer RJ, Antin JH : Prognostic impact of elevated pretransplantation serum ferritin in patients undergoing myeloablative stem cell transplantation. Blood 2007 109 : 4586 4588
46. Thakerngpol K, Fucharoen S, Boonyaphipat P, Srisook K, Sahaphong S, Vathanophas V, Stitnimankarn T : Liver injury due to iron overload in thalassemia: histopathologic and ultrastructural studies. Biometals 1996 9 : 177 183
47. Li CK, Chik KW, Lam CWK, To KF, Yu SCH, Lee V, Shing MMK, Cheung AYK, Yuen PMP : Liver disease in transfusion dependent thalassaemia major. Arch Dis Child 2002 86 : 344 347
48. Angelucci E, Muretto P, Nicolucci A, Baronciani D, Erer B, Gaziev J, Ripalti M, Sodani P, Tomassoni S, Visani G, Lucarelli G : Effects of iron overload and hepatitis C virus positivity in determining progression of liver fibrosis in thalassemia following bone-marrow transplantation. Blood 2002 100 : 17 21
49. Prati D, Maggioni M, Milani S, Cerino M, Cianciulli P, Coggi G, Formi GL, Magnano C, Meo A, Gramignoli R, Rebulla P, Fiorelli G, Cappellini MD Cooleycare Cooperative Group : Clinical and histological characterization of liver disease in patients with transfusion-dependent beta-thalassemia. A multicenter study of 117 cases. Haematologica 2004 89 : 1179 1186
50. Liu P, Olivieri N : Iron overload cardiomyopathies: new insights into an old disease. Cardiovasc Drugs 1994 8 : 101 110
51. Jaeger M, Aul C, Söhngen D, Germing U, Schneider W : Secondary hemochromatosis in polytransfused patients with myelodysplastic syndrome. Beitr Infusionsther 1992 30 : 464 468
52. Wood JC, Enriquez C, Ghugre N, Otto-Duessel M, Aguilar M, Nelson MD, Moats R, Coates TD : Physiology and pathophysiology of iron cardiomyopathy in thalassemia. Ann N Y Acad Sci 2005 1054 : 386 395
53. Goldberg SL, Mody-Patel N, Chen E. Clinical and economic consequences of myelodysplastic syndromes in the United States. An Anal Med Database Blood (ASH Annual Meeting Abstracts) 2008 112 : 636
54. Ong CK, Lim SL, Tan WC, Ong EE, Goh AS : Endocrine complications in transfusion dependent thalassaemia in Penang Hospital. Med J Malaysia 2008 63 : 109 112
55. Toumba M, Serqis A, Kanaris C, Skordis N : Endocrine complications in patients with thalassaemia major. Pediatr Endocrinol Rev 2007 5 : 646 648
56. Fung EB, Harmatz PR, Lee PDK, Milet M, Bellevue R, Jeng MR, Kalinyak KA, Hudes M, Bhatia S, Vichinsky EP : Increased prevalence of iron-overload associated endocrinopathy in thalassaemia versus sickle-cell disease. Br J Haematol 2006 135 : 574 582
57. Axford JS, Bomford A, Revell P, Watt I, Williams R, Hamilton EB : Hip arthropathy in genetic hemochromatosis. Radiographic and histologic features. Arthritis Rheum 1991 34 : 357 361
58. Christenson RA, Pootrakul P, Burnell JM, Teubner EJ, Finch CA, Baylink DJ : Patients with thalassemia develop osteoporosis, osteomalacia, and hypoparathyroidism, all of which are corrected by transfusion. Birth Defects Orig Artic Series 1987 23 : 409 416
59. Voskaridou E, Terpos E : New insights into the pathophysiology and management of osteoporosis in patients with beta thalassemia. Br J Haematol 2004 October 127 : 127 139
60. Vallat JM, Loubet R, Leboutet MJ, Loubet A : Hemosiderin deposition in muscle. Report of three cases. Acta Neuropathol 1978 42 : 153 156
61. Abbott M, Galloway A, Cunningham JL : Haemochromatosis presenting with a double Yersinia infection. J Infect 1986 13 : 143 145
62. Bullen JJ, Spalding PB, Ward CG, Gutteridge JM : Hemochromatosis, iron and septicemia caused by Vibrio vulnificus. Arch Intern Med 1991 151 : 1606 1609
63. Wang L, Johnson EE, Shi HN, Walker WA, Wessling-Resnick M, Cherayil BJ : Attenuated inflammatory responses in hemochromatosis reveal a role for iron in the regulation of macrophage cytokine translation. J Immunol 2008 181 : 2723 2731
64. Brittenham GM, Cohen AR, McLaren CE, Martin MB, Griffith PM, Nienhuis AW, Young NS : 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
65. Edwards CQ, Griffen LM, Kaplan J, Kushner JP : Twenty-four hour variation of transferrin saturation in treated and untreated haemochromatosis homozygotes. J Intern Med 1989 226 : 373 379
66. Borwein S, Ghent CN, Valberg LS : Diagnostic efficacy of screening tests for hereditary hemochromatosis. Can Med Assoc 1984 131 : 895 901
67. Perifanis V, Economou M, Christoforides A, Koussi A, Tsitourides I, Athanassiou-Metaxa M : Evaluation of iron overload in beta-thalassemia patients using magnetic resonance imaging. Hemoglobin 2004 28 : 45 49
68. Shalitin S, Carmi D, Weintrob N, Phillip M, Miskin H, Kornreich L, Zilber R, Yaniv I, Tamary H : Serum ferritin level as a predictor of impaired growth and puberty in thalassemia major patients. Eur J Hematol 2005 74 : 93 100
69. Jensen PD, Jensen FT, Christensen T, Ellegaard J : Evaluation of transfusional iron overload before and during iron chelation by magnetic resonance imaging of the liver and determination of serum ferritin in adult non-thalassemic patients. Br J Haematol 1995 89 : 880 889
70. Herbert V, Jayatilleke E, Shaw S, Rosman AS, Giardina P, Grady RW, Bowman B, Gunter EW : Serum ferritin iron, a new test, measures human body iron stores unconfounded by inflammation. Stem Cells 1997 15 : 291 296
71. Khumalo H, Gomo ZA, Moyo VM, Gordeuk VR, Saungweme T, Rouault TA, Gangaidzo IT : Serum transferrin receptors are decreased in the presence of iron overload. Clin Chem 1998 44 : 40 44
72. Esposito BP, Breuer W, Sirankapracha P, Pootrakul P, Hershko C, Cabantchik ZI : Labile plasma iron in iron overload: redox activity and susceptibility to chelation. Blood 2003 102 : 2670 2677
73. Jacobs EM, Hendriks JC, van Tits BL, Evans PJ, Breuer W, Liu DY, Jansen EH, Jauiainen K, Sturm B, Porter JB, Scheiber-Mojdehkar B, von Bonsdorff L, Cababtchik ZI, Hider RC, Swinkels DW : Results of an international round robin for the quantification of serum non-transferrin-bound iron: need for defining standardization and a clinically relevant isoform. Anal Biochem 2005 341 : 241 250
74. Vermylen C : What is new in iron overload? Eur J Pediatr 2008 167 : 377 381
75. Nielsen P, Engelhardt R, Fischer R, Heinrich HC, Langkowski JH, Bücheler E : Noninvasive liver-iron quantification by computed tomography in iron-overloaded rats. Invest Radiol 1992 27 : 312 317
76. Wielopolski L, Zaino EC : Noninvasive in-vivo measurement of hepatic and cardiac iron. J Nuc Med 1992 33 : 1278 1282
77. Jensen PD : Evaluation of iron overload. Br J Haematol 2004 124 : 697 711
78. Wood JC, Enriquez C, Ghugre N, Tyzka JM, Carson S, Nelson MD, Coates TD : MRI R2 and R2* mapping accurately estimates hepatic iron concentration in transfusion-dependent thalassemia and sickle cell disease patients. Blood 2005 106 : 1460 1465
79. Neufeld EJ : Oral chelators deferasirox and deferiprone for transfusional iron overload in thalassemia major: new data, new questions. Blood 2006 107 : 3436 3441
80. 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
81. Ernst O, Sergent G, Bonvarlet P, Canva-Delcambre V, Paris JC, L'Herminé C : Hepatic iron overload: diagnosis and quantification with MR imaging. AJR Am J Roentgenol 1997 168 : 1205 1208
82. Gandon Y, Guyader D, Heautot JF, Reda MI, Yaouanq J, Buhé T, Brissot P, Carsin M, Deugnier Y : Hemochromatosis: diagnosis and quantification of liver iron with gradient-echo MR imaging. Radiology 1994 193 : 533 538
83. St Pierre TG, Clark PR, Chua-anusorn 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 (Pubitemid 40070775)
84. Tanner MA, Galanello R, Dessi C, Westwood MA, Smith GC, Nair SV, Anderson LJ, Walker JM, Pennell DJ : Myocardial iron loading in patients with thalassemia major on deferoxamine chelation. J Cardiovasc Magn Reson 2006 8 : 543 547
85. Wood JC, Origa R, Agus A, Matta G, Coates TD, Galanello R : Onset of cardiac iron loading in pediatric patients with thalassemia major. Haematologica 2008 93 : 917 920
86. Lau KY, Chan YI, Lam WW, Li CK, Metreweli C : Magnetic resonance imaging evaluation of the pituitary gland and hypothalamus in thalassaemic children with elevated serum ferritin levels. J Paediatr Child Health 1998 34 : 463 466
87. Fischer R, Piga A, Harmatz P, Nielsen P : Monitoring long-term efficacy of iron chelation treatment with biomagnetic liver susceptometry. Ann N Y Acad Sci 2005 1054 : 350 357
88. Weigand K, Weigand K : Percutaneous liver biopsy: retrospective study over 15 years comparing 287 in patients with 428 outpatients. J Gastroenterol Hepatol 2009 February 4 [Epub ahead of print]
89. Brittenham GM, Griffith PM, Nienhuis AW, McLaren CE, Young NS, Tucker EE, Allen CJ, Farrell DE, Harris JW : Efficacy of deferoxamine in preventing complications of iron overload in patients with thalassemia major. N Engl J Med 1994 331 : 567 573
90. Basset ML, Halliday JW, Powell LW : Value of hepatic iron measurements in early hemochromatosis and determination of the critical iron level associated with fibrosis. Hepatology 1986 6 : 24 29
91. Jensen PD, Jensen FT, Christensen T, Nielsen JL, Ellegaard J : Relationship between hepatocellular injury and transfusional iron overload prior to and during iron chelation with desferrioxamine: a study in adult patients with acquired anemias. Blood 2003 101 : 91 96
92. Olson LJ, Edwards WD, Mccall JT, Ilstrup DM, Gersh BJ : Cardiac iron deposition in idiopathic hemochromatosis, histologic and analytic assessment of 14 hearts from autopsy. J Am Coll Cardiol 1987 10 : 1239 1243
93. Gattermann N : Overview of guidelines on iron chelation therapy in patients with myelodysplastic syndromes and transfusional iron overload. Int J Hematol 2008 88 : 24 29
94. Angelucci E, Barosi G, Camaschella C, Cappelini MS, Cazzola M, Galanello R, Marchetti M, Piga A, Tura S : Italian Society of Hematology practice guidelines for the management of iron overload in thalassemia major and related disorders. Haematologica 2008 93 : 741 752
95. Tavill AS : Diagnosis and management of hemochromatosis. AASLD Practice Guidelines. Hepatology 2001 33 : 1321 1327
96. National Comprehensive Cancer Network : NCCN Clinical Practice Guidelines in Oncology - v.1.2009: Myelodysplastic Syndromes. Accessed on December 19, 2008 at: http://www.nccn.org/professionals/physician-gls/pdf/mds.pdf
97. Gattermann N, Porter J, Lopes LF, Seymour J : Consensus statement on iron overload in myelodysplastic syndromes. Hematol Oncol Clin 2005 19 (Suppl. 1 18 25
98. Mittelman M, Lugassy G, Merkel D, Tamary H, Sarid N, Rachmilewitz E, Hershko C : Iron chelation therapy in patients with myelodysplastic syndromes: consensus conference guidelines. Isr Med Assoc J 2008 10 : 374 376
99. Gattermann N : Guidelines on iron chelation therapy in patients with myelodysplastic syndromes and transfusional iron overload. Leuk Res 2007 31 (Suppl. 3 S10 S15
100. Cappellini MD : Long-term efficacy and safety of deferasirox. Blood Rev 2008 22 (Suppl. 2 S35 S41
101. Cohen AR : New advances in iron chelation therapy. Hematology 2006 1 : 42 47
102. Cappellini MD, El-Beshlawy A, Kattamis A, Lee JW, Seymour JF, Li C-K, Habr D, Domokos G, Hmissi A, Elalfy MS : Efficacy and safety of deferasirox (Exjade®) in patients with transfusion-dependent anemias: 1-year results from the large, prospective, multicenter EPIC study. Presented at the Annual Meeting of the American Society of Hematology. December 6-9, 2008; San Francisco, California. Poster III-957
103. Pennell D, Sutcharitchan P, El-Beshlawy A, Aydinok Y, Taher A, Smith G, Habr D, Kriemler-Krahn U, Hmissi A, Porter JB : Efficacy and safety of deferasirox (Exjade®) in preventing cardiac iron overload in β-thalassemia patients with normal baseline cardiac iron: results from the cardiac substudy of the EPIC trial. Presented at the Annual Meeting of the American Society of Hematology. December 6-9, 2008; San Francisco, California. Poster III-956
104. Desferal Prescribing Information. Accessed on December 19, 2008 at: http://www.fda.gov/cder/foi/label/2001/16267s34lbl.pdf