Role and regulation of iron metabolism in erythropoiesis and disease

  • Tara L. Arvedson
  • Barbra J. Sasu
Part of the Milestones in Drug Therapy book series (MDT)


Iron is an essential element for normal cellular metabolism and growth as an enzyme cofactor, heme constituent and oxygenation sensor. In excess however, free iron is toxic. Living organisms have, therefore, evolved sophisticated and tightly regulated mechanisms to control iron uptake, transport, and release. Defects in any part of this process can lead to disease. For example, excessive uptake can lead to systemic iron overload and associated toxicity. Inappropriate or inefficient transport can lead to iron maldistribution or deficiency. Red blood cells are the primary consumers of iron and the largest body iron pool (approximately 50% of the body’s iron is incorporated in heme); hence, fluctuations in iron supply can have significant effects on red blood cell production and function. This chapter provides an overview of the proteins and pathways involved in iron metabolism as they relate to normal red blood cell biology and disorders of iron excess or deficiency.


Iron Deficiency Serum Ferritin Iron Overload Iron Deficiency Anemia Iron Uptake 
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  1. 1.
    Gunshin H, Mackenzie B, Berger UV et al. Cloning and characterization of a mammalian proton-coupled metal-ion transporter. Nature 1997;388:482–488.PubMedGoogle Scholar
  2. 2.
    Liuzzi JP, Aydemir F, Nam H et al. Zip14 (slc39a14) mediates non-transferrin-bound iron uptake into cells. Proc Natl Acad Sci USA 2006;103:13612–13617.PubMedGoogle Scholar
  3. 3.
    McKie AT, Barrow D, Latunde-Dada GO et al. An iron-regulated ferric reductase associated with the absorption of dietary iron. Science 2001;291:1755–1759.PubMedGoogle Scholar
  4. 4.
    Gunshin H, Starr CN, DiRenzo C et al. Cybrd1 (duodenal cytochrome b) is not necessary for dietary iron absorption in mice. Blood 2005;106:2879–2883.PubMedGoogle Scholar
  5. 5.
    Shayeghi M, Latunde-Dada GO et al. Identification of an intestinal heme transporter. Cell 2005;122:789–801.PubMedGoogle Scholar
  6. 6.
    Qiu A, Jansen M, Sakaris A et al. Identification of an intestinal folate transporter and the molecular basis for hereditary folate malabsorption. Cell 2006;127:917–928.PubMedGoogle Scholar
  7. 7.
    Parmley RT, Barton JC, Conrad ME et al. Ultrastructural cytochemistry and radioautography of hemoglobin — iron absorption. Exp Mol Pathol 1981;34:131–144.PubMedGoogle Scholar
  8. 8.
    Donovan A, Lima CA, Pinkus JL et al. The iron exporter ferroportin/slc40a1 is essential for iron homeostasis. Cell Metab 2005;1:191–200.PubMedGoogle Scholar
  9. 9.
    Vulpe CD, Kuo Y-M, Murphy TL et al. Hephaestin, a ceruloplasmin homologue implicated in intestinal iron transport, is defective in the sla mouse. Nat Genet 1999;21:195–199.PubMedGoogle Scholar
  10. 10.
    Harris ZL, Durley AP, Man TK et al. Targeted gene disruption reveals an essential role for ceruloplasmin in cellular iron efflux. Proc Natl Acad Sci USA 1999;96:10812–10817.PubMedGoogle Scholar
  11. 11.
    Sharp P. The molecular basis of copper and iron interactions. Proc Nutrition Soc 2004;63:563–569.Google Scholar
  12. 12.
    Aisen P, Leibman A, Zweier J. Stoichiometric and site characteristics of the binding of iron to human transferrin. J Biol Chem 1978;253:1930–1937.PubMedGoogle Scholar
  13. 13.
    Wada HG, Hass PE, Sussman HH. Transferrin receptor in human placental brush border membranes. Studies on the binding of transferrin to placental membrane vesicles and the identification of a placental brush border glycoprotein with high affinity for transferrin. J Biol Chem 1979;254:12629–12635.PubMedGoogle Scholar
  14. 14.
    Paterson S, Armstrong NJ, Iacopetta BJM et al. Intravesicular ph and iron uptake by immature erythroid cells. J Cell Physiol 1984;120:225–232.PubMedGoogle Scholar
  15. 15.
    Graham RM, Chua AC, Herbison CE et al. Liver iron transport. World. J Gastroenterol 2007;13:4725–4736.Google Scholar
  16. 16.
    Jandl JH, Katz JH. The plasma-to-cell cycle of transferrin. J Clin Invest 1963;42:314–326.PubMedGoogle Scholar
  17. 17.
    Trinder D, Morgan E. Uptake of transferrin-bound iron by mammalian cells, in Templeton DM (ed.) Molecular and cellular iron transport. Toronto, Marcel Dekker, Inc., 2002;427–442.Google Scholar
  18. 18.
    Brissot P, Pigeon C, Loreal O. Regulation of systemic iron transport and storage; in Templeton DM (ed.) Molecular and cellular iron transport. Toronto, Marcel Dekker, Inc. 2002;597–609.Google Scholar
  19. 19.
    Ma Y, Yeh M, Yeh K-Y et al. Iron imports. V. Transport of iron through the intestinal epithelium. Am J Physiol Gastrointest Liver Physiol 2006;290:G417–422.PubMedGoogle Scholar
  20. 20.
    Arosio P, Levi S. Ferritin, iron homeostasis, and oxidative damage. Free Radical BiolMed 2002;33:457–463.Google Scholar
  21. 21.
    Cragg SJ, Wagstaff M, Worwood M. Detection of a glycosylated subunit in human serum ferritin. Biochem J 1981;199:565–571.PubMedGoogle Scholar
  22. 22.
    Halliday JW, Powell LW. Ferritin metabolism and the liver. Sem Liver Dis 1984;4:207–216.Google Scholar
  23. 23.
    Blight GD, Morgan EH. Ferritin and iron uptake by reticulocytes. Br J Haematol 1983;55:59–71.PubMedGoogle Scholar
  24. 24.
    Loken MR, Shah VO, Dattilio KL et al. Flow cytometric analysis of human bone marrow: I. Normal erythroid development. Blood 1987;69:255–263.PubMedGoogle Scholar
  25. 25.
    Smith DW. The molecular biology of mammalian hemoglobin synthesis. Ann Clin Lab Sci 1980;10:116–122.PubMedGoogle Scholar
  26. 26.
    Shaw GC, Cope JJ, Li L et al. Mitoferrin is essential for erythroid iron assimilation. Nature 2006;440:96–100.PubMedGoogle Scholar
  27. 27.
    Napier I, Ponka P, Richardson DR. Iron trafficking in the mitochondrion: Novel pathways revealed by disease. Blood 2005;105:1867–1874.PubMedGoogle Scholar
  28. 28.
    Quigley JG, Yang Z, Worthington MT et al. Identification of a human heme exporter that is essential for erythropoiesis. Cell 2004;118:757–766.PubMedGoogle Scholar
  29. 29.
    Jonker JW, Buitelaar M, Wagenaar E et al. The breast cancer resistance protein protects against a major chlorophyll-derived dietary phototoxin and protoporphyria. Proc Natl Acad Sci USA 2002;99:15649–15654.PubMedGoogle Scholar
  30. 30.
    Shirihai OS, Gregory T, Yu C et al. Abc-me: A novel mitochondrial transporter induced by gata-1 during erythroid differentiation. EMBO J 2000;19:2492–2502.PubMedGoogle Scholar
  31. 31.
    Allen DW, Jandl JH. Kinetics of intracellular iron in rabbit reticulocytes. Blood 1960;15:71–81.PubMedGoogle Scholar
  32. 32.
    Noyes WD, Hosain F, Finch CA. Incorporation of radioiron into heme. J Lab Clin Med 1964;64:574–580.PubMedGoogle Scholar
  33. 33.
    Fontenay M, Cathelin S, Amiot M et al. Mitochondria in hematopoiesis and hematological diseases. Oncogene 2006;25:4757–4767.PubMedGoogle Scholar
  34. 34.
    Beutler E. Hemolytic anemia due to chemical and physical agents. In Beutler E, Coller BS, Lichtman MA, Kipps TJ, Seligsohn U (eds): Williams hematology. McGraw-Hill, 2001;629–632.Google Scholar
  35. 35.
    Bowman WDJ. Abnormal (“Ringed”) sideroblasts in various hematologic and non-hematologic disorders. Blood 1961;18:662–671.PubMedGoogle Scholar
  36. 36.
    Bekri S, May A, Cotter PD et al. A promoter mutation in the erythroid-specific 5-aminolevulinate synthase (alas2) gene causes x-linked sideroblastic anemia. Blood 2003;102:698–704.PubMedGoogle Scholar
  37. 37.
    Taketani S, Adachi Y, Nakahashi Y. Regulation of the expression of human ferrochelatase by intracellular iron levels. Eur J Biochem 2000;267:4685–4692.PubMedGoogle Scholar
  38. 38.
    Tahara T, Sun J, Igarashi K et al. Heme-dependent up-regulation of the [alpha]-globin gene expression by transcriptional repressor bach 1 in erythroid cells. Biochem Biophys Res Commun 2004;324:77–85.PubMedGoogle Scholar
  39. 39.
    Alter BP, Goff SC. Globin synthesis in mouse erythroleukemia cells in vitro: A switch in beta chains due to inducing agent. Blood 1977;50:867–876.PubMedGoogle Scholar
  40. 40.
    Cotter PD, Baumann M, Bishop DF. Enzymatic defect in “X-linked” Sideroblastic anemia: Molecular evidence for erythroid {delta}-aminolevulinate synthase deficiency. Proc Natl Acad Sci USA 1992;89:4028–4032.PubMedGoogle Scholar
  41. 41.
    Cotter PD, May A, Li L et al. Four new mutations in the erythroid-specific 5-aminolevulinate synthase (alas2) gene causing x-linked sideroblastic anemia: Increased pyridoxine responsiveness after removal of iron overload by phlebotomy and coinheritance of hereditary hemochromatosis. Blood 1999;93:1757–1769.PubMedGoogle Scholar
  42. 42.
    Bottomley S, Tanaka M, Everett M. Diminished erythroid ferrochelatase activity protoporphyria. J Lab Clin Med 1975;86:126–131.PubMedGoogle Scholar
  43. 43.
    Borgna-Pignatti C, Galanello R. Thalassemias and related disorders: Quantitative disorders of hemoglobin synthesis.; Wintrobe’s clinical hematology. Philadephia, Lippincott, Williams and Wilkins, 2004;1319–1365.Google Scholar
  44. 44.
    Bratosin D, Mazurier J, Tissier JP et al. Cellular and molecular mechanisms of senescent erythrocyte phagocytosis by macrophages. A review. Biochimie 1998;80:173–195.PubMedGoogle Scholar
  45. 45.
    Biggs TE, Baker ST, Botham MS et al. Nrampl modulates iron homoeostasis in vivo and in vitro: Evidence for a role in cellular iron release-involving de-acidification of intracellular vesicles. Eur J Immunol 2001;31:2060–2070.PubMedGoogle Scholar
  46. 46.
    Jabado N, Canonne-Hergaux F, Gruenheid S et al. Iron transporter nramp2/dmt-1 is associated with the membrane of phagosomes in macrophages and sertoli cells. Blood 2002;100:2617–2622.PubMedGoogle Scholar
  47. 47.
    Delaby C, Pilard N, Puy H et al. Sequential regulation of ferroportin expression after erythrophagocytosis in murine macrophages: Early mrna induction by haem, followed by iron-dependent protein expression. Biochem J 2008;411:123–131.PubMedGoogle Scholar
  48. 48.
    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.PubMedGoogle Scholar
  49. 49.
    Park CH, Valore EV, Waring AJ et al. Hepcidin, a urinary antimicrobial peptide synthesized in the liver. J Biol Chem 2001;276:7806–7810.PubMedGoogle Scholar
  50. 50.
    Pigeon C, Ilyin G, Courseland 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.PubMedGoogle Scholar
  51. 51.
    Laftah AH, Ramesh B, Simpson RJ et al. Effect of hepcidin on intestinal iron absorption in mice. Blood 2004;103:3940–3944.PubMedGoogle Scholar
  52. 52.
    Yeh KY, Yeh M, Glass J. Hepcidin regulation of ferroportin 1 expression in the liver and intestine of the rat. Am J Physiol GastroLiver Physiol 2004;286:G385–394.Google Scholar
  53. 53.
    Frazer DM, Wilkins SJ, Becker EM et al. Hepcidin expression inversely correlates with the expression of duodenal iron transporters and iron absorption in rats. Gastroenterology 2002;123:835–844.PubMedGoogle Scholar
  54. 54.
    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.PubMedGoogle Scholar
  55. 55.
    Kulaksiz H, Theilig F, Bachmann S et al. The iron-regulatory peptide hormone hepcidin: Expression and cellular localization in the mammalian kidney. J Endocrinol 2005;184:361–370.PubMedGoogle Scholar
  56. 56.
    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.PubMedGoogle Scholar
  57. 57.
    Ilyin G, Courselaud B, Troadec MB et al. Comparative analysis of mouse hepcidin 1 and 2 genes: Evidence for different patterns of expression and co-inducibility during iron overload. FEBS Lett 2003;542:22–26.PubMedGoogle Scholar
  58. 58.
    Peyssonnaux C, Zinkernagel AS, Datta V et al. Tlr4-dependent hepcidin expression by myeloid cells in response to bacterial pathogens. Blood 2006;107:3727–3732.PubMedGoogle Scholar
  59. 59.
    Guana-prakasam JP, Martin PM, Mysona BA et al. Hepcidin expression in mouse retina and its regulation via lipopolysaccharide/toll-like receptor-4 pathway independent of hfe. Biochem J 2008;411:79–88.Google Scholar
  60. 60.
    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.PubMedGoogle Scholar
  61. 61.
    Lesbordes-Brion JC, Viatte L, Bennoun M et al. Targeted disruption of the hepcidin 1 gene results in severe hemochromatosis. Blood 2006;108:1402–1405.PubMedGoogle Scholar
  62. 62.
    Nicolas G, Bennoun M, Porteu A et al. Severe iron deficiency anemia in transgenic mice expressing liver hepcidin. Proc Natl Acad Sci USA 2002;99:4596–4601.PubMedGoogle Scholar
  63. 63.
    Roetto A, Papanikolaou G, Politou M et al. Mutant antimicrobial peptide hepcidin is associated with severe juvenile hemochromatosis. Nature Gen 2003;33:21–22.Google Scholar
  64. 64.
    Weinstein DA, Roy CN, Fleming MD et al. Inappropriate expression of hepcidin is associated with iron refractory anemia: Implications for the anemia of chronic disease. Blood 2002;100:3776–3781.PubMedGoogle Scholar
  65. 65.
    Schmidt PJ, Huang FW, Wrighting DM et al. Hepcidin expression is regulated by a complex of hemochromatosis-associated proteins. Blood 2006;108: abstract 267Google Scholar
  66. 66.
    Schmidt PJ, Toran PT, Giannetti AM et al. The transferrin receptor modulates hfe-dependent regulation of hepcidin expression. Cell Metab 2008;7:205–214.PubMedGoogle Scholar
  67. 67.
    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.PubMedGoogle Scholar
  68. 68.
    Babitt JL, Huang FW, Wrighting DM et al. Bone morphogenetic protein signaling by hemojuvelin regulates hepcidin expression. Nature Gen 2006;38:531–539.Google Scholar
  69. 69.
    Nicolas G, Chauvet C, Viatte L et al. The gene encoding the iron regulatory peptide hepcidin is regulated by anemia, hypoxia, and inflammation. J Clin Invest 2002;110:1037–1044.PubMedGoogle Scholar
  70. 70.
    Pak M, Lopez MA, Gabayan V et al. Suppression of hepcidin during anemia requires erythropoietic activity. Blood 2006;108:3730–3735.PubMedGoogle Scholar
  71. 71.
    Nemeth E, Rivera S, Gabayan V et al. II-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepeidin. J Clin Invest 2004;113:1251–1253.Google Scholar
  72. 72.
    Lee P, Peng H, Gelbart T et al. Regulation of hepcidin transcription by interleukin-1 and interleukin-6. Proc Natl Acad Sci USA 2005;102:1906–1910.PubMedGoogle Scholar
  73. 73.
    Wrighting DM, Andrews NC. Interleukin-6 induces hepcidin expression through stat3. Blood 2006;108:3204–3209.PubMedGoogle Scholar
  74. 74.
    Jean G, Terzoli S, Mauri R et al. Cirrhosis associated with multiple transfusions in thalassaemia. Arch Dis Child 1984;59:67–70.PubMedGoogle Scholar
  75. 75.
    Kushner JP, Porter JP, Olivieri NF: Secondary iron overload. Hematology Am Soc Hematol Educ Program 2001:47–61.Google Scholar
  76. 76.
    Nemeth E, Ganz T. Regulation of iron metabolism by hepcidin. Annu Rev Nutr 2006;26:323–342.PubMedGoogle Scholar
  77. 77.
    Waalen J, Beutler E. Hereditary hemochromatosis: Screening and management. Curr Hematol Rep 2006;5:34–40.PubMedGoogle Scholar
  78. 78.
    Yen AW, Fancher TL, Bowlus CL et al. Revisiting hereditary hemochromatosis: Current concepts and progress. Am J Med 2006;119:391–399.PubMedGoogle Scholar
  79. 79.
    De Gobbi M, Roetto A, Piperno A et al. Natural history of juvenile haemochromatosis. Br J Haematol 2002;117:973–979.PubMedGoogle Scholar
  80. 80.
    Lamon JM, Marynick SP, Roseblatt R et al. Idiopathic hemochromatosis in a young female. A case study and review of the syndrome in young people. Gastroenterology 1979;76:178–183.PubMedGoogle Scholar
  81. 81.
    Pietrangelo A, Caleffi A, Henrion J et al. Juvenile hemochromatosis associated with pathogenic mutations of adult hemochromatosis genes. Gastroenterology 2005;128:470–479.PubMedGoogle Scholar
  82. 82.
    Brissot P, de Bels F. Current approaches to the management of hemochromatosis. Hematol Am Soc Hematol Educ Program 2006;36–41.Google Scholar
  83. 83.
    Jabbour E, Kantarjian HM, Koller C et al. Red blood cell transfusions and iron overload in the treatment of patients with myelodysplastic syndromes. Cancer 2008;112:1089–1095.PubMedGoogle Scholar
  84. 84.
    Beutler E, Hoffbrand AV, Cook JD. Iron deficiency and overload. Hematol Am Soc Hematol Educ Program 2003;2003:40–61.Google Scholar
  85. 85.
    Besarab A. Resolving the paradigm crisis in intravenous iron and erythropoietin management. Kidney Int Suppl 2006;101:S13–18.Google Scholar
  86. 86.
    Cook JD, Skikne BS, Baynes RD. Iron deficiency: The global perspective. Adv Exp Med Biol 1994;356:219–228.PubMedGoogle Scholar
  87. 87.
    d’Onofrio G, Kuse R, Foures C et al. Reticulocytes in haematological disorders. Clin Lab Haematol 1996;18:29–34.PubMedGoogle Scholar
  88. 88.
    Brugnara C. Reticulocyte cellular indices: A new approach in the diagnosis of anemias and monitoring of erythropoietic function. Crit Rev Clin Lab Sci 2000;37:93–130.PubMedGoogle Scholar
  89. 89.
    Thomas C, Thomas L. Biochemical markers and hematologic indices in the diagnosis of functional iron deficiency. Clin Chem 2002;48:1066–1076.PubMedGoogle Scholar
  90. 90.
    Katodritou E, Terpos E, Zervas K et al. Hypochromic erythrocytes (%): A reliable marker for recognizing iron-restricted erythropoiesis and predicting response to erythropoietin in anemic patients with myeloma and lymphoma. Ann Hematol 2007;86:369–376.PubMedGoogle Scholar
  91. 91.
    Brugnara C. Iron deficiency and erythropoiesis: New diagnostic approaches. Clin Chem 2003;49:1573–1578.PubMedGoogle Scholar
  92. 92.
    Sengoelge G, Sunder-Plassmann G, Hörl WH. Potential risk for infection and atherosclerosis due to iron therapy. J Ren Nutr 2005;15:105–110.PubMedGoogle Scholar
  93. 93.
    Burns DL, Pomposelli JJ. Toxicity of parenteral iron dextran therapy. Kidney Int Suppl 1999;69:S119–124.Google Scholar
  94. 94.
    Besarab A, Amin N, Ahsan M et al. Optimization of epoetin therapy with intravenous iron therapy in hemodialysis patients. J Am Soc Nephrol 2000;11:530–538.PubMedGoogle Scholar
  95. 95.
    Eschbach JW, Egrie JC, Downing MR et al. Correction of the anemia of end-stage renal disease with recombinant human erythropoietin. Results of a combined phase I and II clinical trial. N Engl J Med 1987;316:73–78.PubMedGoogle Scholar
  96. 96.
    Kemna E, Pickkers P, Nemeth E et al. Time-course analysis of hepcidin, serum iron, and plasma cytokine levels in humans injected with lps. Blood 2005;106:1864–1866.PubMedGoogle Scholar
  97. 97.
    Nemeth E, Valore EV, Territo M et al. Hepcidin, a putative mediator of anemia of inflammation, is a type ii acute-phase protein. Blood 2003;101:2461–2463.PubMedGoogle Scholar
  98. 98.
    Roy CN, Weinstein DA, Andrews NC. The molecular biology of the anemia of chronic disease: A hypothesis. Fed Res 2003;53:507–512.Google Scholar
  99. 99.
    Ganz T. Hepcidin, a key regulator of iron metabolism and mediator of anemia of inflammation. Blood 2003;102:783–788.PubMedGoogle Scholar
  100. 100.
    Andrews NC. Anemia of inflammation: The cytokine hepcidin link. J Clin Invest 2004; 113:1251–1253.PubMedGoogle Scholar
  101. 101.
    Horl WH, Jacobs C, Macdougall IC et al. European best practice guidelines 17–18: Adverse effects. Nephrol Dial Transplant 2000;15:S4:51–56.Google Scholar
  102. 102.
    Horl WH, Jacobs C, Macdougall IC et al. European best practice guidelines 14–16: Inadequate response to epoetin. Nephrol Dial Transplant 2000;15:S4:43–50.Google Scholar
  103. 103.
    Barany P, Divino-Filho JC, Bergstrom J. High c-reactive protein is a strong predictor of resistance to erythropoietin in hemodialysis patients. Am J Kidney Dis 1997;29:565–568.PubMedGoogle Scholar
  104. 104.
    Qureshi AR, Alvestrand A, Danielsson A et al. Factors predicting malnutrition in hemodialysis patients: A cross-sectional study. Kidney Int 1998;53:773–782.PubMedGoogle Scholar
  105. 105.
    Yeun JY, Levine RA, Mantadilok V et al. C-reactive protein predicts all-cause and cardiovascular mortality in hemodialysis patients. Am J Kidney Dis 2000;35:469–476.PubMedGoogle Scholar
  106. 106.
    Zimmermann J, Herrlinger S, Pruy A et al. Inflammation enhances cardiovascular risk and mortality in hemodialysis patients. Kidney Int 1999;55:648–658.PubMedGoogle Scholar
  107. 107.
    Fine A. Relevance of c-reactive protein levels in peritoneal dialysis patients. Kidney Int 2002;61:615–620.PubMedGoogle Scholar
  108. 108.
    Bertero MT, Caligaris-Cappio F. Anemia of chronic disorders in systemic autoimmune diseases. Haematology 1997;82:375–381.Google Scholar
  109. 109.
    Nanas JN, Matsouka C. Karageorgopoulos D et al. Etiology of anemia in patients with advanced heart failure. J Am Coll Cardiol 2006;48:2485–2489.PubMedGoogle Scholar
  110. 110.
    Pieracci FM, Barie PS. Diagnosis and management of iron-related anemias in critical illness. Crit Care Med 2006;34:1898–1905.PubMedGoogle Scholar
  111. 111.
    Punnonen K, Irjala K, Rajamaki A. Serum transferrin receptor and its ratio to serum ferritin in the diagnosis of iron deficiency. Blood 1997;89:1052–1057.PubMedGoogle Scholar
  112. 112.
    Weiss G, Goodnough LT. Anemia of chronic disease. N Engl J Med 2005;352:1011–1023.PubMedGoogle Scholar
  113. 113.
    Kemna EHJM, Tjalsma H, Willems HL et al. Hepcidin: From discovery to differential diagnosis. Haematol 2008;93:90–97.Google Scholar
  114. 114.
    Ganz T. Molecular control of iron transport. J Am Soc Nephrol 2007;18:394–400.PubMedGoogle Scholar
  115. 115.
    Cartwright GE. The anemia of chronic disorders. Semin Hematol 1966;3:351–375.PubMedGoogle Scholar
  116. 116.
    Means RT Jr, Advances in the anemia of chronic disease. Int J Hematol 1999;70:7–12.PubMedGoogle Scholar
  117. 117.
    Yuan XM, Li W, Yuan X-M et al. The iron hypothesis of atherosclerosis and its clinical impact. Ann Med 2003;35:578–591.PubMedGoogle Scholar
  118. 118.
    Viatte L, Nicolas G, Lou D-Q et al. Chronic hepcidin induction causes hyposideremia and alters the pattern of cellular iron accumulation in hemochromatotic mice. Blood 2006;107:2952–2958.PubMedGoogle Scholar
  119. 119.
    Kawabata H, Tomosugi N, Kanda J et al. Anti-interleukin 6 receptor antibody tocilizumab reduces the level of serum hepcidin in patients with multicentric castleman’s disease. Haematologica 2007;92:857–858.PubMedGoogle Scholar
  120. 120.
    Lagsetmo I, Young B, Zhang W et al. Effect of fg-2216 on anemia and iron transport in a rat model of anemia of chronic disease. J Am Soc Nephrol 2004;15:548A.Google Scholar

Copyright information

© Birkhäuser Verlag/Switzerland 2009

Authors and Affiliations

  • Tara L. Arvedson
    • 1
  • Barbra J. Sasu
    • 1
  1. 1.Amgen Inc.Thousand OaksUSA

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