Blood Reviews
Volume 22, Issue 4 , Pages 195-210 , July 2008

Current approach to hemochromatosis

  • Pierre Brissot

      Affiliations

    • Liver Disease Unit, Liver Research Unit Inserm U-522, IFR 140, University of Rennes1, Hemochromatosis Reference Center, France
    • Corresponding Author InformationCorresponding author. Tel.: +33 299282442; fax: +33 299284112.
    • ,
  • Marie-Bérengère Troadec

      Affiliations

    • Liver Disease Unit, Liver Research Unit Inserm U-522, IFR 140, University of Rennes1, Hemochromatosis Reference Center, France
    • ,
  • Edouard Bardou-Jacquet

      Affiliations

    • Liver Disease Unit, Liver Research Unit Inserm U-522, IFR 140, University of Rennes1, Hemochromatosis Reference Center, France
    • ,
  • Caroline Le Lan

      Affiliations

    • Liver Disease Unit, Liver Research Unit Inserm U-522, IFR 140, University of Rennes1, Hemochromatosis Reference Center, France
    • ,
  • Anne-Marie Jouanolle

      Affiliations

    • Liver Disease Unit, Liver Research Unit Inserm U-522, IFR 140, University of Rennes1, Hemochromatosis Reference Center, France
    • Laboratory of Molecular Genetics, University Hospital Pontchaillou, Rennes, France
    • ,
  • Yves Deugnier

      Affiliations

    • Liver Disease Unit, Liver Research Unit Inserm U-522, IFR 140, University of Rennes1, Hemochromatosis Reference Center, France
    • ,
  • Olivier Loréal

      Affiliations

    • Liver Disease Unit, Liver Research Unit Inserm U-522, IFR 140, University of Rennes1, Hemochromatosis Reference Center, France

References 

  1. Feder JN, Gnirke A, Thomas W, et al. A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis. Nat Genet. 1996;13:399–408
  2. Brissot P, Troadec MB, Loreal O. The clinical relevance of new insights in iron transport and metabolism. Curr Hematol Rep. 2004;3:107–115
  3. Loreal O, Haziza-Pigeon C, Troadec MB, et al. Hepcidin in iron metabolism. Curr Protein Pept Sci. 2005;6:279–291
  4. Camaschella C. Understanding iron homeostasis through genetic analysis of hemochromatosis and related disorders. Blood. 2005;106:3710–3717
  5. Deugnier Y, Brissot P, Loréal O. Iron and the Liver: Update 2008. J Hepatol 2008:in press.
  6. OMIM. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=omim.
  7. Brissot P, Le Lan C, Troadec MB, et al.: Diagnosis and Treatment of HFE-haemochromatosis. In: Handbook ESoH, ed. Disorders of Iron homeostasis, Erythrocytes, Erythropoiesis, 2006.
  8. Pietrangelo A. Hemochromatosis: an endocrine liver disease. Hepatology. 2007;46:1291–1301
  9. Merryweather-Clarke AT, Pointon JJ, Shearman JD, Robson KJ. Global prevalence of putative haemochromatosis mutations. J Med Genet. 1997;34:275–278
  10. Poddar S. Hereditary hemochromatosis-Special reference to Indian scenario. Int J Human Genet. 2006;6:73–79
  11. Dhillon BK, Das R, Garewal G, et al. Frequency of primary iron overload and HFE gene mutations (C282Y, H63D and S65C) in chronic liver disease patients in north India. World J Gastroenterol. 2007;13:2956–2959
  12. Waalen J, Nordestgaard BG, Beutler E. The penetrance of hereditary hemochromatosis. Best Pract Res Clin Haematol. 2005;18:203–220
  13. Beutler E, Felitti VJ, Koziol JA, Ho NJ, Gelbart T. Penetrance of 845G–> A (C282Y) HFE hereditary haemochromatosis mutation in the USA. Lancet. 2002;359:211–218
  14. Adams PC, Reboussin DM, Barton JC, et al. Hemochromatosis and iron-overload screening in a racially diverse population. N Engl J Med. 2005;352:1769–1778
  15. Powell LW, Dixon JL, Ramm GA, et al. Screening for hemochromatosis in asymptomatic subjects with or without a family history. Arch Intern Med. 2006;166:294–301
  16. Asberg A, Hveem K, Halvorsen TB, Smethurst HB. Prevalence of liver fibrosis and cirrhosis in screening-detected C282Y homozygous subjects. Scand J Gastroenterol. 2007;42:782–783
  17. van der AD, Peeters PH, Grobbee DE, Roest M, Voorbij HA, van der Schouw YT. HFE genotypes and dietary heme iron: no evidence of strong gene-nutrient interaction on serum ferritin concentrations in middle-aged women. Nutr Metab Cardiovasc Dis. 2006;16:60–68
  18. Cade JE, Moreton JA, O’Hara B, et al. Diet and genetic factors associated with iron status in middle-aged women. Am J Clin Nutr. 2005;82:813–820
  19. Kaltwasser JP, Werner E, Schalk K, Hansen C, Gottschalk R, Seidl C. Clinical trial on the effect of regular tea drinking on iron accumulation in genetic haemochromatosis. Gut. 1998;43:699–704
  20. Barton JC, Preston BL, McDonnell SM, Rothenberg BE. Severity of iron overload in hemochromatosis: effect of volunteer blood donation before diagnosis. Transfusion. 2001;41:123–129
  21. Distante S, Berg JP, Lande K, Haug E, Bell H. HFE gene mutation (C282Y) and phenotypic expression among a hospitalised population in a high prevalence area of haemochromatosis. Gut. 2000;47:575–579
  22. Beutler E, Waalen J, Gelbart T. Chronic inflammation does not appear to modify the homozygous hereditary hemochromatosis phenotype. Blood Cells Mol Dis. 2005;35:326–327
  23. Beutler E, Gelbart T. Helicobacter pylori infection and HFE hemochromatosis. Blood Cells Mol Dis. 2006;37:188–191
  24. Detivaud L, Nemeth E, Boudjema K, et al. Hepcidin levels in humans are correlated with hepatic iron stores, hemoglobin levels, and hepatic function. Blood. 2005;106:746–748
  25. Bridle K, Cheung TK, Murphy T, et al. Hepcidin is down-regulated in alcoholic liver injury: implications for the pathogenesis of alcoholic liver disease. Alcohol Clin Exp Res. 2006;30:106–112
  26. Harrison-Findik DD, Schafer D, Klein E, et al. Alcohol metabolism-mediated oxidative stress down-regulates hepcidin transcription and leads to increased duodenal iron transporter expression. J Biol Chem. 2006;281:22974–22982
  27. Laine F, Jouannolle AM, Morcet J, et al. Phenotypic expression in detected C282Y homozygous women depends on body mass index. J Hepatol. 2005;43:1055–1059
  28. Bekri S, Gual P, Anty R, et al. Increased adipose tissue expression of hepcidin in severe obesity is independent from diabetes and NASH. Gastroenterology. 2006;131:788–796
  29. Hutchinson C, Geissler CA, Powell JJ, Bomford A. Proton pump inhibitors suppress absorption of dietary non-haem iron in hereditary haemochromatosis. Gut. 2007;56:1291–1295
  30. Moirand R, Adams PC, Bicheler V, Brissot P, Deugnier Y. Clinical features of genetic hemochromatosis in women compared with men. Ann Intern Med. 1997;127:105–110
  31. Deugnier Y, Jouanolle AM, Chaperon J, et al. Gender-specific phenotypic expression and screening strategies in C282Y-linked haemochromatosis: a study of 9396 french people. Br J Haematol. 2002;118:1170–1178
  32. Olynyk JK, Cullen DJ, Aquilia S, Rossi E, Summerville L, Powell LW. A population-based study of the clinical expression of the hemochromatosis gene. N Engl J Med. 1999;341:718–724
  33. Asberg A, Hveem K, Thorstensen K, et al. Screening for hemochromatosis: high prevalence and low morbidity in an unselected population of 65,238 persons. Scand J Gastroenterol. 2001;36:1108–1115
  34. Levy JE, Montross LK, Andrews NC. Genes that modify the hemochromatosis phenotype in mice. J Clin Invest. 2000;105:1209–1216
  35. Bensaid M, Fruchon S, Mazeres C, Bahram S, Roth MP, Coppin H. Multigenic control of hepatic iron loading in a murine model of hemochromatosis. Gastroenterology. 2004;126:1400–1408
  36. Tolosano E, Fagoonee S, Garuti C, et al. Haptoglobin modifies the hemochromatosis phenotype in mice. Blood. 2005;105:3353–3355
  37. Jacolot S, Le Gac G, Scotet V, Quere L, Muraz C, Ferec C. HAMP as a modifier gene that increase the phenotypic expression of the HFE C282Y homozygous genotype. Blood. 2004;103:2340–2385
  38. Merryweather-Clarke AT, Cadet E, Bomford A, et al. Digenic inheritance of mutations in HAMP and HFE results in different types of haemochromatosis. Hum Mol Genet. 2003;12:2241–2247
  39. Le Gac G, Scotet V, Ka C, et al. The recently identifiedtype 2A juvenile haemochromatosis gene (HJV), a seconf candidate modifier of the C282Y homozygous phenotype. Hum Mol Genet. 2004;13:1913–1918
  40. Millet J, Dehais V, Bourgain C, et al. Common variants in the BMP2, BMP4, and HJV genes of the hepcidin regulation pathway module HFE hemochromatosis penetrance. Am J Human Genet. 2007;81:799–807
  41. Lee P, Gelbart T, West C, Halloran C, Beutler E. Seeking candidate mutations that affect iron homeostasis. Blood Cells Mol Dis. 2002;29:471–487
  42. Carter K, Bowen DJ, McCune CA, Worwood M. Haptoglobin type neither influences iron accumulation in normal subjects nor predicts clinical presentation in HFE C282Y haemochromatosis: phenotype and genotype analysis. Br J Haematol. 2003;122:326–332
  43. Kelleher T, Ryan E, Barrett S, O’Keane C, Crowe J. DMT1 genetic variability is not responsible for phenotype variability in hereditary hemochromatosis. Blood Cells Mol Dis. 2004;33:35–39
  44. Gochee PA, Powell LW, Cullen DJ, Du Sart D, Rossi E, Olynyk JK. A population-based study of the biochemical and clinical expression of the H63D hemochromatosis mutation. Gastroenterology. 2002;122:646–651
  45. Walsh A, Dixon JL, Ramm GA, et al. The clinical relevance of compound heterozygosity for the C282Y and H63D substitutions in hemochromatosis. Clin Gastroenterol Hepatol. 2006;4:1403–1410
  46. Papanikolaou G, Samuels ME, Ludwig EH, et al. Mutations in HFE2 cause iron overload in chromosome 1q-linked juvenile hemochromatosis. Nat Genet. 2004;36:77–82
  47. Roetto A, Papanikolaou G, Politou M, et al. Mutant antimicrobial peptide hepcidin is associated with severe juvenile hemochromatosis. Nat Genet. 2003;33:21–22
  48. Roetto A, Totaro A, Piperno A, et al. New mutations inactivating transferrin receptor 2 in hemochromatosis type 3. Blood. 2001;97:2555–2560
  49. Girelli D, Bozzini C, Roetto A, et al. Clinical and pathologic findings in hemochromatosis type 3 due to a novel mutation in transferrin receptor 2 gene. Gastroenterology. 2002;122:1295–1302
  50. Majore S, Milano F, Binni F, et al. Homozygous p.M172K mutation of the TFR2 gene in an Italian family with type 3 hereditary hemochromatosis and early onset iron overload. Haematologica. 2006;91:ECR33
  51. Pietrangelo A. The ferroportin disease. Blood Cells Mol Dis. 2004;32:131–138
  52. Wallace DF, Subramaniam VN. Non-HFE haemochromatosis. World J Gastroenterol. 2007;13:4690–4698
  53. Montosi G, Donovan A, Totaro A, et al. Autosomal-dominant hemochromatosis is associated with a mutation in the ferroportin (SLC11A3) gene. J Clin Invest. 2001;108:619–623
  54. Njajou OT, Vaessen N, Joosse M, et al. A mutation in SLC11A3 is associated with autosomal dominant hemochromatosis. Nat Genet. 2001;28:213–214
  55. Barton JC, Acton RT, Lee PL, West C. SLC40A1 Q248H allele frequencies and Q248H-associated risk of non-HFE iron overload in persons of sub-Saharan African descent. Blood Cells Mol Dis. 2007;39:206–211
  56. Beutler E, Barton JC, Felitti VJ, et al. Ferroportin 1 (SCL40A1) variant associated with iron overload in African-Americans. Blood Cells Mol Dis. 2003;31:305–309
  57. Rivers CA, Barton JC, Gordeuk VR, et al. Association of ferroportin Q248H polymorphism with elevated levels of serum ferritin in African Americans in the Hemochromatosis and Iron Overload Screening (HEIRS) Study. Blood Cells Mol Dis. 2007;38:247–252
  58. Subramaniam VN, Wallace DF, Dixon JL, Fletcher LM, Crawford DH. Ferroportin disease due to the A77D mutation in Australia. Gut. 2005;54:1048–1049
  59. Koyama C, Wakusawa S, Hayashi H, et al. A Japanese family with ferroportin disease caused by a novel mutation of SLC40A1 gene: hyperferritinemia associated with a relatively low transferrin saturation of iron. Intern Med. 2005;44:990–993
  60. Hsiao PJ, Tsai KB, Shin SJ, et al. A novel mutation of transferrin receptor 2 in a Taiwanese woman with type 3 hemochromatosis. J Hepatol. 2007;47:303–306
  61. Agarwal S, Sankar VH, Tewari D, Pradhan M. Ferroportin (SLC40A1) gene in thalassemic patients of Indian descent. Clin Genet. 2006;70:86–87
  62. Wallace DF, Clark RM, Harley HA, Subramaniam VN. Autosomal dominant iron overload due to a novel mutation of ferroportin1 associated with parenchymal iron loading and cirrhosis. J Hepatol. 2004;40:710–713
  63. Sham RL, Phatak PD, West C, Lee P, Andrews C, Beutler E. Autosomal dominant hereditary hemochromatosis associated with a novel ferroportin mutation and unique clinical features. Blood Cells Mol Dis. 2005;34:157–161
  64. Miyajima H, Takahashi Y, Kono S. Aceruloplasminemia, an inherited disorder of iron metabolism. Biometals. 2003;16:205–213
  65. Yoshida K, Furihata K, Takeda S, et al. A mutation in the ceruloplasmin gene is associated with systemic hemosiderosis in humans. Nat Genet. 1995;9:267–272
  66. Kono S, Suzuki H, Takahashi K, et al. Hepatic iron overload associated with a decreased serum ceruloplasmin level in a novel clinical type of aceruloplasminemia. Gastroenterology. 2006;131:240–245
  67. Knisely AS, Gelbart T, Beutler E. Molecular characterization of a third case of human atransferrinemia. Blood. 2004;104:2607
  68. Mims MP, Guan Y, Pospisilova D, et al. Identification of a human mutation of DMT1 in a patient with microcytic anemia and iron overload. Blood. 2005;105:1337–1342
  69. Beaumont C, Delaunay J, Hetet G, Grandchamp B, de Montalembert M, Tchernia G. Two new human DMT1 gene mutations in a patient with microcytic anemia, low ferritinemia, and liver iron overload. Blood. 2006;107:4168–4170
  70. Iolascon A, d’Apolito M, Servedio V, Cimmino F, Piga A, Camaschella C. Microcytic anemia and hepatic iron overload in a child with compound heterozygous mutations in DMT1 (SCL11A2). Blood. 2006;107:349–354
  71. Camaschella C, Campanella A, De Falco L, et al. The human counterpart of zebrafish shiraz shows sideroblastic-like microcytic anemia and iron overload. Blood. 2007;110:1353–1358
  72. Krause A, Neitz S, Magert HJ, et al. LEAP-1, a novel highly disulfide-bonded human peptide, exhibits antimicrobial activity. FEBS Lett. 2000;480:147–150
  73. Park CH, Valore EV, Waring AJ, Ganz T. Hepcidin, a urinary antimicrobial peptide synthesized in the liver. J Biol Chem. 2001;276:7806–7810
  74. Pigeon C, Ilyin G, Courselaud B, et al. A new mouse liver-specific gene, encoding a protein homologous to human antimicrobial peptide hepcidin, is overexpressed during iron overload. J Biol Chem. 2001;276:7811–7819
  75. Peyssonnaux C, Zinkernagel AS, Datta V, Lauth X, Johnson RS, Nizet V. TLR4-dependent hepcidin expression by myeloid cells in response to bacterial pathogens. Blood. 2006;107:3727–3732
  76. Nemeth E, Valore EV, Territo M, Schiller G, Lichtenstein A, Ganz T. Hepcidin, a putative mediator of anemia of inflammation, is a type II acute-phase protein. Blood. 2003;101:2461–2463
  77. Nicolas G, Viatte L, Bennoun M, Beaumont C, Kahn A, Vaulont S. Hepcidin, A New Iron Regulatory Peptide. Blood Cells Mol Dis. 2002;29:327–335
  78. Ganz T. Molecular control of iron transport. J Am Soc Nephrol. 2007;18:394–400
  79. Andrews NC, Schmidt PJ. Iron homeostasis. Annu. Rev. Physiol. 2006;69:16.11–16.17
  80. Nemeth E, Tuttle MS, Powelson J, et al. Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science. 2004;306:2090–2093
  81. Rivera S, Nemeth E, Gabayan V, Lopez MA, Farshidi D, Ganz T. Synthetic hepcidin causes rapid dose-dependent hypoferremia and is concentrated in ferroportin-containing organs. Blood. 2005;2196–2199
  82. Courselaud B, Pigeon C, Inoue Y, et al. C/EBPalpha regulates hepatic transcription of hepcidin, an antimicrobial peptide and regulator of iron metabolism. Cross-talk between C/EBP pathway and iron metabolism. J Biol Chem. 2002;277:41163–41170
  83. Babitt JL, Huang FW, DM W, et al. Bone morphogenetic protein signaling by hemojuvelin regulates hepcidin expression. Nat Genet. 2006;38:531–539
  84. Wang R, Li C, Xu X, et al. A role of SMAD4 in iron metabolism through the positive regulation of hepcidin expression. Cell Metab. 2005;2:399–409
  85. Truksa J, Peng H, Lee P, Beutler E. Bone morphogenetic proteins 2, 4, and 9 stimulate murine hepcidin1 expression independently of Hfe, transferrin receptor 2. Proc Natl Acad Sci U S A 2006:10289–10293.
  86. Goswami T, Andrews NC. Hereditary hemochromatosis protein, HFE, interaction with transferrin receptor 2 suggests a molecular mechanism for mammalian iron sensing. J Biol Chem. 2006;281:28494–28498
  87. Calzolari A, Raggi C, Deaglio S, et al. TfR2 localizes in lipid raft domains and is released in exosomes to activate signal transduction along the MAPK pathway. J Cell Sci. 2006;119:4486–4498
  88. Silvestri L, Pagani A, Camaschella C. Furin mediated release of soluble hemojuvelin: a new link between hypoxia and iron homeostasis. Blood. 2007;
  89. Valore EV, Ganz T. Posttranslational processing of hepcidin in human hepatocytes is mediated by the prohormone convertase furin. Blood Cells Mol Dis. 2008;40:132–138
  90. Nicolas G, Bennoun M, Devaux I, et al. Lack of hepcidin gene expression and severe tissue iron overload in upstream stimulatory factor 2 (USF2) knockout mice. Proc Natl Acad Sci USA. 2001;98:8780–8785
  91. Papanikolaou G, Tzilianos M, Christakis JI, et al. Hepcidin in iron overload disorders. Blood. 2005;105:4103–4105
  92. Hershko C, Graham G, Bates GW, Rachmilewitz EA. Non-specific serum iron in thalassaemia: an abnormal serum iron fraction of potential toxicity. Br J Haematol. 1978;40:255–263
  93. Hider RC. Nature of nontransferrin-bound iron. Eur J Clin Invest. 2002;32(Suppl 1):50–54
  94. Brissot P, Wright TL, Ma WL, Weisiger RA. Efficient clearance of non-transferrin-bound iron by rat liver. Implications for hepatic iron loading in iron overload states. J Clin Invest. 1985;76:1463–1470
  95. 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
  96. Le Lan C, Loreal O, Cohen T, et al. Redox active plasma iron in C282Y/C282Y hemochromatosis. Blood. 2005;105:4527–4531
  97. Drakesmith H, Schimanski LM, Ormerod E, et al. Resistance to hepcidin is conferred by hemochromatosis-associated mutations of ferroportin. Blood. 2005;106:1092–1097
  98. De Domenico I, Ward DM, Musci G, Kaplan J. Iron overload due to mutations in ferroportin. Haematologica. 2006;91:92–95
  99. De Domenico I, Ward DM, di Patti MC, et al. Ferroxidase activity is required for the stability of cell surface ferroportin in cells expressing GPI-ceruloplasmin. Embo J. 2007;26:2823–2831
  100. Moirand R, Kerdavid F, Loreal O, et al. Regulation of ferritin expression by alcohol in a human hepatoblastoma cell line and in rat hepatocyte cultures. J Hepatol. 1995;23:431–439
  101. Mendler MH, Turlin B, Moirand R, et al. Insulin resistance-associated hepatic iron overload. Gastroenterology. 1999;117:1155–1163
  102. Loreal O, Nemeth E, Le Lan C, et al. Abnormal expression of hepcidin during genetic hemochromatosis, alcoholic cirrhosis,and dysmetabolic hepatosiderosis-Abstract. International Bio-Iron Society.Kyoto.April, 1–6,2007. Am J Hematol 2008;in press.
  103. Ferrante M, Geubel A, Fevery J, Marogy G, Horsmans Y, Nevens F. Hereditary hyperferritinaemia-cataract syndrome: a challenging diagnosis for the hepatogastroenterologist. Eur J Gastroenterol Hepatol. 2005;17:1247–1253
  104. Pinto L, Kagalwala F, Singh S, Balakrishnan C, Prabhu SV, Khodaiji S. Macrophage activation syndrome: experience from a tertiary referral centre. J Assoc Physicians India. 2007;55:185–187
  105. Gandon Y, Olivié D, Guyader D, et al. Non-invasive assessment of hepatic iron stores by MRI. Lancet. 2004;33:338–343
  106. St Pierre TG, Clark PR, Chua-anusorn W, et al. Noninvasive measurement and imaging of liver iron concentrations using proton magnetic resonance. Blood. 2005;105:855–861
  107. Pietrangelo A, Corradini E, Ferrara F, et al. Magnetic resonance imaging to identify classic and nonclassic forms of ferroportin disease. Blood Cells Mol Dis. 2004;37:192–196
  108. Deugnier Y, Turlin B. Pathology of hepatic iron overload. World J Gastroenterol. 2007;13:4755–4760
  109. Sebastiani G, Alberti A. Non invasive fibrosis biomarkers reduce but not substitute the need for liver biopsy. World J Gastroenterol. 2006;12:3682–3694
  110. Stauber RE, Lackner C. Noninvasive diagnosis of hepatic fibrosis in chronic hepatitis C. World J Gastroenterol. 2007;13:4287–4294
  111. Deugnier Y, Loreal O, Carre F, et al. Increased body iron stores in elite road cyclists. Med Sci Sports Exerc. 2002;34:876–880
  112. Tanno T, Bhanu NV, Oneal PA, et al. High levels of GDF15 in thalassemia suppress expression of the iron regulatory protein hepcidin. Nat Med. 2007;13:1096–1101
  113. Piperno A, Girelli D, Nemeth E, et al. Blunted hepcidin response to oral iron challenge in HFE-related hemochromatosis. Blood. 2007;110:4096–4100
  114. Piperno A, Roetto A, Mariani R, et al. Homozygosity for transferrin receptor-2 Y250X mutation induces early iron overload. Haematologica. 2004;89:359–360
  115. Le Gac G, Mons F, Jacolot S, Scotet V, Ferec C, Frebourg T. Early onset hereditary hemochromatosis resulting from a novel TFR2 gene nonsense mutation (R105X) in two siblings of north French descent. Br J Haematol. 2004;125:674–678
  116. HAS. French recommendations for management of HFE hemochromatosis. Haute Autorité de Santé 2005; www.has-sante.fr.
  117. Brissot P, de Bels F. Current approaches to the management of hemochromatosis. Hematology Am Soc Hematol Educ Program. 2006;36–41
  118. Loreal O, Turlin B, Pigeon C, et al. Aceruloplasminemia: new clinical, pathophysiological and therapeutic insights. J Hepatol. 2002;36:851–856
  119. Roberts DJ, Brunskill SJ, Doree C, Williams S, Howard J, Hyde CJ. Oral deferiprone for iron chelation in people with thalassaemia. Cochrane Database Syst Rev 2007:CD004839.
  120. Henter JI, Karlen J. Fatal agranulocytosis after deferiprone therapy in a child with Diamond-Blackfan anemia. Blood. 2007;109:5157–5159
  121. 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;107:3455–3462
  122. Adams PC, Reboussin DM, Press RD, et al. Biological variability of transferrin saturation and unsaturated iron-binding capacity. Am J Med. 2007;120:999 e991–999 e997
  123. Waalen J, Felitti VJ, Gelbart T, Beutler E. Screening for hemochromatosis by measuring ferritin levels: a more effective approach. Blood. 2007;

PII: S0268-960X(08)00020-9

doi: 10.1016/j.blre.2008.03.001

Blood Reviews
Volume 22, Issue 4 , Pages 195-210 , July 2008

Article Tools

* Image Usage & Resolution