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36 - Management of iron overload

Published online by Cambridge University Press:  01 June 2011

James C. Barton ,
Corwin Q. Edwards ,
Pradyumna D. Phatak ,
Robert S. Britton  and
Bruce R. Bacon
By
James C. Barton ,
Corwin Q. Edwards ,
Pradyumna D. Phatak ,
Robert S. Britton  and
Bruce R. Bacon
James C. Barton
Affiliation:
University of Alabama, Birmingham
Corwin Q. Edwards
Affiliation:
University of Utah Medical Center
Pradyumna D. Phatak
Affiliation:
University of Rochester Medical Center, New York
Robert S. Britton
Affiliation:
St Louis University, Missouri
Bruce R. Bacon
Affiliation:
St Louis University, Missouri
James C. Barton
Affiliation:
University of Alabama, Birmingham
Corwin Q. Edwards
Affiliation:
University of Utah School of Medicine, Salt Lake City
Pradyumna D. Phatak
Affiliation:
University of Rochester Medical Center, New York
Robert S. Britton
Affiliation:
St Louis University, Missouri
Bruce R. Bacon
Affiliation:
St Louis University, Missouri
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Summary

Iron overload is characterized by excessive iron deposition in and consequent injury and dysfunction of target organs, especially the heart, liver, anterior pituitary, pancreas, and joints (Chapter 5). Because physiologic mechanisms to excrete iron are very limited, patients with iron overload and its complications need safe, effective therapy that is compatible with their co-existing medical conditions. Worldwide, prevention of death due to cardiac siderosis is the most important potential benefit of therapy. The incidence of cardiac complications is greatest in patients with beta-thalassemia major and other heritable anemias treated with multiple transfusions. The liver is the primary target organ of iron overload in hemochromatosis and African iron overload, although maintaining normal hepatic function is important in all patients with iron overload. Preventing injury to endocrine organs is critical in children with iron overload. Successful treatment or prevention of iron overload increases quality of life and survival in many patients.

Therapeutic phlebotomy removes iron as hemoglobin, and is thus suitable for treatment of patients with iron overload without severe anemia in whom erythropoiesis is fundamentally normal (Table 36.1). Many reports substantiate the effectiveness, outcomes, and safety of phlebotomy therapy in HFE hemochromatosis and allied disorders. Chelation therapy employs drugs that preferentially bind excess iron and increase its excretion (Table 36.1). Some dietary maneuvers may decrease the absorption of dietary iron, and may be useful as adjunctive therapy for some patients with iron overload, although such treatments do not diminish body iron burdens.

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Information
Handbook of Iron Overload Disorders , pp. 321 - 341
Publisher: Cambridge University Press
Print publication year: 2010

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References

Barton, JC. Optimal management strategies for chronic iron overload. Drugs 2007; 67: 68500.CrossRefGoogle ScholarPubMed
Barton, JC, McDonnell, SM, Adams, PC, et al. Management of hemochromatosis. Hemochromatosis Management Working Group. Ann Intern Med 1998; 129: 932–9.CrossRefGoogle ScholarPubMed
Beutler, E, Hoffbrand, AV, Cook, JD. Iron deficiency and overload. Hematology (Am Soc Hematol Educ Program) 2003; 40–61.Google ScholarPubMed
Angelucci, E, Muretto, P, Lucarelli, G, et al. Phlebotomy to reduce iron overload in patients cured of thalassemia by bone marrow transplantation. Italian Cooperative Group for Phlebotomy Treatment of Transplanted Thalassemia Patients. Blood 1997; 90: 994–8.Google Scholar
Barton, JC, Bertoli, LF. Transfusion iron overload in adults with acute leukemia: manifestations and therapy. Am J Med Sci 2000; 319: 73–8.CrossRefGoogle ScholarPubMed
Edwards, CQ, Griffen, LM, Goldgar, D, Drummond, C, Skolnick, MH, Kushner, JP. Prevalence of hemochromatosis among 11,065 presumably healthy blood donors. N Engl J Med 1988; 318: 1355–62.CrossRefGoogle ScholarPubMed
Barton, JC, Grindon, AJ, Barton, NH, Bertoli, LF. Hemochromatosis probands as blood donors. Transfusion 1999; 39: 578–85.CrossRefGoogle ScholarPubMed
Levstik, M, Adams, PC. Eligibility and exclusion of hemochromatosis patients as voluntary blood donors. Can J Gastroenterol 1998; 12: 61–3.CrossRefGoogle ScholarPubMed
Leitman, SF, Browning, JN, Yau, YY, et al. Hemochromatosis subjects as allogeneic blood donors: a prospective study. Transfusion 2003; 43: 1538–44.CrossRefGoogle ScholarPubMed
Power, TE, Adams, PC. Hemochromatosis patients as voluntary blood donors. Can J Gastroenterol 2004; 18: 393–6.CrossRefGoogle ScholarPubMed
Hicken, BL, Tucker, DC, Barton, JC. Patient compliance with phlebotomy therapy for iron overload associated with hemochromatosis. Am J Gastroenterol 2003; 98: 2072.CrossRefGoogle ScholarPubMed
Lim, FL, Dooley, JS, Roques, AW, Grellier, L, Dhillon, AP, Walker, AP. Hepatic iron concentration, fibrosis and response to venesection associated with the A77D and V162del “loss-of-function” mutations in ferroportin disease. Blood Cells Mol Dis 2008; 40: 328–33.
McDonnell, SM, Grindon, AJ, Preston, BL, Barton, JC, Edwards, CQ, Adams, PC. A survey of phlebotomy among persons with hemochromatosis. Transfusion 1999; 39: 651–6.CrossRefGoogle ScholarPubMed
Bilgrami, S, Bartolomeo, A, Synnott, V, Rickles, FR. Management of hemosiderosis complicated by co-existent anemia with recombinant human erythropoietin and phlebotomy. Acta Haematol 1993; 89: 141–3.CrossRefGoogle Scholar
Gobbi, M, Pasquero, P, Brunello, F, Paccotti, P, Mazza, U, Camaschella, C. Juvenile hemochromatosis associated with β-thalassemia treated by phlebotomy and recombinant human erythropoietin. Haematologica 2000; 85: 865.Google ScholarPubMed
Mariani, R, Pelucchi, S, Perseghin, P, Corengia, C, Piperno, A. Erythrocytapheresis plus erythropoietin: an alternative therapy for selected patients with hemochromatosis and severe organ damage. Haematologica 2005; 90: 717–18.Google ScholarPubMed
St. Pierre, TG, Jeffrey, GP, Rossi, E, et al. A new model for predicting venesection therapy requirements in hereditary hemochromatosis using non-invasive liver iron concentration measurement [abstract]. Blood 2005; 106: Abstract 3596.Google Scholar
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: 105–10.CrossRefGoogle Scholar
Witte, DL, Crosby, WH, Edwards, CQ, Fairbanks, VF, Mitros, FA. Practice guideline development task force of the College of American Pathologists. Hereditary hemochromatosis. Clin Chim Acta 1996; 245: 139–200.CrossRefGoogle ScholarPubMed
Barton, JC, Preston, BL, McDonnell, SM, Rothenberg, BE. Severity of iron overload in hemochromatosis: effect of volunteer blood donation before diagnosis. Transfusion 2001; 41: 123–9.CrossRefGoogle ScholarPubMed
Barisani, D, Ceroni, S, Del Bianco, S, Meneveri, R, Bardella, MT. Hemochromatosis gene mutations and iron metabolism in celiac disease. Haematologica 2004; 89: 1299–305.Google ScholarPubMed
Barton, JC. Hemochromatosis, HFE C282Y homozygosity, and bariatric surgery: report of three cases. Obes Surg 2004; 14: 1409–14.CrossRefGoogle ScholarPubMed
Barton, JC, Bertoli, LF, Rothenberg, BE. Peripheral blood erythrocyte parameters in hemochromatosis: evidence for increased erythrocyte hemoglobin content. J Lab Clin Med 2000; 135: 96–104.CrossRefGoogle ScholarPubMed
Bolan, CD, Conry-Cantilena, C, Mason, G, Rouault, TA, Leitman, SF. MCV as a guide to phlebotomy therapy for hemochromatosis. Transfusion 2001; 41: 819–27.CrossRefGoogle ScholarPubMed
McLaren, CE, Barton, JC, Gordeuk, VR, et al. Determinants and characteristics of mean corpuscular volume and hemoglobin concentration in white HFE C282Y homozygotes in the hemochromatosis and iron overload screening study. Am J Hematol 2007; 82: 898–905.CrossRefGoogle Scholar
Adams, PC, Barton, JC. Haemochromatosis. Lancet 2007; 370: 1855–60.CrossRefGoogle ScholarPubMed
Adams, PC, Kertesz, AE, Valberg, LS.Rate of iron reaccumulation following iron depletion in hereditary hemochromatosis. Implications for venesection therapy. J Clin Gastroenterol 1993; 16: 207–10.CrossRefGoogle ScholarPubMed
Adams, PC. Factors affecting the rate of iron mobilization during venesection therapy for genetic hemochromatosis. Am J Hematol 1998; 58: 16–19.3.0.CO;2-3>CrossRefGoogle ScholarPubMed
Barton, JC, Bottomley, SS. Iron deficiency due to excessive therapeutic phlebotomy in hemochromatosis. Am J Hematol 2000; 65: 223–6.3.0.CO;2-9>CrossRefGoogle ScholarPubMed
Barton, JC, Wooten, VD, Acton, RT. Hemochromatosis and iron therapy of restless legs syndrome. Sleep Med 2001; 2: 2491.CrossRefGoogle ScholarPubMed
Barton, JC, Beutler, E, Gelbart, T. Coinheritance of alleles associated with hemochromatosis and hereditary hyperferritinemia-cataract syndrome. Blood 1998; 92: 4480.Google ScholarPubMed
Fraquelli, M, Mandelli, C, Cesarini, L, Barisani, D, Bianchi, PA, Conte, D.[Survival and development of neoplasms in 56 patients with idiopathic hemochromatosis.]Ann Ital Med Int 1992; 7: 26–9.Google Scholar
Kohan, A, Niborski, R, Daruich, J, et al. Erythrocytapheresis with recombinant human erythropoietin in hereditary hemochromatosis therapy: a new alternative. Vox Sang 2000; 79: 40.CrossRefGoogle ScholarPubMed
Raj, AB, Condurache, T, Bertolone, S, Williams, D, Lorenz, D, Sobczyk, W. Quantitative assessment of ventricular function in sickle cell disease: effect of long-term erythrocytapheresis. Pediatr Blood Cancer 2005; 45: 976–81.CrossRefGoogle ScholarPubMed
Hershko, C, Link, G, Konijn, AM. Chelation therapy in iron overload. In: Barton, JC, Edwards, CQ, eds. Hemochromatosis. Genetics, Pathophysiology, Diagnosis and Treatment. Cambridge, Cambridge University Press. 2000; 3394.CrossRefGoogle Scholar
Barton, JC. Chelation therapy for iron overload. Curr Gastroenterol Rep 2007; 9: 74–82.CrossRefGoogle ScholarPubMed
Neufeld, EJ. Oral chelators deferasirox and deferiprone for transfusional iron overload in thalassemia major: new data, new questions. Blood 2006; 107: 3436–41.CrossRefGoogle Scholar
Porter, JB, Abeysinghe, RD, Marshall, L, Hider, RC, Singh, S. Kinetics of removal and reappearance of non-transferrin-bound plasma iron with deferoxamine therapy. Blood 1996; 88: 705–13.Google ScholarPubMed
Bothwell, TH, Bradlow, BA, Jacobs, P, et al. Iron metabolism in scurvy with special reference to erythropoiesis. Br J Haematol 1964; 10: 50–8.CrossRefGoogle ScholarPubMed
Lipschitz, DA, Bothwell, TH, Seftel, HC, Wapnick, AA, Charlton, RW. The role of ascorbic acid in the metabolism of storage iron. Br J Haematol 1971; 20: 155–63.CrossRefGoogle Scholar
Banerjee, S, Chakrabarty, AS. Utilization of iron by scorbutic guinea pigs. Blood 1965; 25: 839–44.Google ScholarPubMed
Chapman, RW, Hussain, MA, Gorman, A, et al. Effect of ascorbic acid deficiency on serum ferritin concentration in patients with beta-thalassaemia major and iron overload. J Clin Pathol 1982; 35: 487–91.CrossRefGoogle ScholarPubMed
Cohen, A, Cohen, IJ, Schwartz, E. Scurvy and altered iron stores in thalassemia major. N Engl J Med 1981; 304: 158–60.CrossRefGoogle ScholarPubMed
Lynch, SR, Seftel, HC, Torrance, JD, Charlton, RW, Bothwell, TH. Accelerated oxidative catabolism of ascorbic acid in siderotic Bantu. Am J Clin Nutr 1967; 20: 641.CrossRefGoogle ScholarPubMed
Wapnick, AA, Lynch, SR, Charlton, RW, Seftel, HC, Bothwell, TH. The effect of ascorbic acid deficiency on desferrioxamine-induced urinary iron excretion. Br J Haematol 1969; 17: 563–8.CrossRefGoogle ScholarPubMed
O'Brien, RT. Ascorbic acid enhancement of desferrioxamine-induced urinary iron excretion in thalassemia major. Ann NY Acad Sci 1974; 232: 221.CrossRefGoogle ScholarPubMed
Nienhuis, AW. Vitamin C and iron. N Engl J Med 1981; 304: 170–1.CrossRefGoogle ScholarPubMed
Thalassemia major: molecular and clinical aspects. NIH Conference. Ann Intern Med 1979; 91: 883–97.
Rowbotham, B, Roeser, HP. Iron overload associated with congenital pyruvate kinase deficiency and high-dose ascorbic acid ingestion. Aust NZ J Med 1984; 14: 667–9.CrossRefGoogle ScholarPubMed
McLaran, CJ, Bett, JH, Nye, JA, Halliday, JW. Congestive cardiomyopathy and haemochromatosis-rapid progression possibly accelerated by excessive ingestion of ascorbic acid. Aust NZ J Med 1982; 12: 187–8.CrossRefGoogle ScholarPubMed
Porter, JB. Practical management of iron overload. Br J Haematol 2001; 115: 2392.CrossRefGoogle ScholarPubMed
Gabutti, V, Piga, A. Results of long-term iron-chelating therapy. Acta Haematol 1996; 95: 26–36.CrossRefGoogle ScholarPubMed
Araujo, A, Kosaryan, M, MacDowell, A, et al. A novel delivery system for continuous desferrioxamine infusion in transfusional iron overload. Br J Haematol 1996; 93: 835.CrossRefGoogle ScholarPubMed
Borgna-Pignatti, C, Cohen, A. Evaluation of a new method of administration of the iron chelating agent deferoxamine. J Pediatr 1997; 130: 86–8.CrossRefGoogle ScholarPubMed
Davis, BA, Porter, JB. Results of long-term iron chelation treatment with deferoxamine. Adv Exp Med Biol 2002; 509: 91–125.CrossRefGoogle ScholarPubMed
Anderson, LJ, Wonke, B, Prescott, E, Holden, S, Walker, JM, Pennell, DJ. Comparison of effects of oral deferiprone and subcutaneous desferrioxamine on myocardial iron concentrations and ventricular function in beta-thalassaemia. Lancet 2002; 360: 516–20.CrossRefGoogle ScholarPubMed
Liu, DY, Liu, ZD, Hider, RC. Oral iron chelators-development and application. Best Pract Res Clin Haematol 2002; 15: 369–84.CrossRefGoogle ScholarPubMed
Pennell, DJ, Berdoukas, V, Karagiorga, M, et al. Randomized controlled trial of deferiprone or deferoxamine in beta-thalassemia major patients with asymptomatic myocardial siderosis. Blood 2006; 107: 3738–44.CrossRefGoogle ScholarPubMed
Taher, A, Sheikh-Taha, M, Koussa, S, Inati, A, Neeman, R, Mourad, F. Comparison between deferoxamine and deferiprone (L1) in iron-loaded thalassemia patients. Eur J Haematol 2001; 67: 30–4.CrossRefGoogle ScholarPubMed
Piga, A, Gaglioti, C, Fogliacco, E, Tricta, F. Comparative effects of deferiprone and deferoxamine on survival and cardiac disease in patients with thalassemia major: a retrospective analysis. Haematologica 2003; 88: 489–96.Google ScholarPubMed
Borgna-Pignatti, C, Cappellini, MD, Stefano, P, et al. Cardiac morbidity and mortality in deferoxamine- or deferiprone-treated patients with thalassemia major. Blood 2006; 107: 3733.CrossRefGoogle ScholarPubMed
Cappellini, MD, Cohen, A, Piga, A, et al. A phase III study of deferasirox (ICL670), a once-daily oral iron chelator, in patients with beta-thalassemia. Blood 2006; 107: 3455–62.CrossRefGoogle Scholar
Barton, JC. Deferasirox Novartis. Curr Opin Investig Drugs 2005; 6: 327–35.Google ScholarPubMed
Barton, JC.Drug evaluation: Deferitrin for iron overload disorders. IDrugs 2007; 10: 480–90.Google ScholarPubMed
Mukhopadhyay, S, Mukhopadhyay, A, Gupta, PR, Kar, M, Ghosh, A. The role of iron chelation activity of wheat grass juice in blood transfusion requirement of intermediate thalassemia [abstract]. ASH Annual Meeting Abstracts 2007; 110: 3289.Google Scholar
Mukhopadhyay, S, Basak, J, Kar, M, Mandal, S, Mukhopadhyay, A. The role of iron chelation activity of wheat grass juice in patients with myelodysplastic syndrome [abstract]. ASCO Meeting Abstracts 2009; 27: 7012.Google Scholar
Jiao, Y, Wilkinson, J, Christine, PE, et al. Iron chelation in the biological activity of curcumin. Free Radic Biol Med 2006; 40: 1152–60.CrossRefGoogle ScholarPubMed
Ludwiczek, S, Theurl, I, Muckenthaler, MU, et al. Ca2+ channel blockers reverse iron overload by a new mechanism via divalent metal transporter-1. Nat Med 2007; 13: 4484.CrossRefGoogle ScholarPubMed
Olivieri, NF, Nathan, DG, MacMillan, JH, et al. Survival in medically treated patients with homozygous beta-thalassemia. N Engl J Med 1994; 331: 574–8.CrossRefGoogle ScholarPubMed
Brittenham, GM, Griffith, PM, Nienhuis, AW, et al. Efficacy of deferoxamine in preventing complications of iron overload in patients with thalassemia major. N Engl J Med 1994; 331: 5673.CrossRefGoogle ScholarPubMed
Hoffbrand, AV, Cohen, A, Hershko, C. Role of deferiprone in chelation therapy for transfusional iron overload. Blood 2003; 102: 17–24.CrossRefGoogle ScholarPubMed
Fischer, R, Longo, F, Nielsen, P, Engelhardt, R, Hider, RC, Piga, A. Monitoring long-term efficacy of iron chelation therapy by deferiprone and desferrioxamine in patients with beta-thalassaemia major: application of SQUID biomagnetic liver susceptometry. Br J Haematol 2003; 121: 938–48.CrossRefGoogle ScholarPubMed
Wonke, B, Wright, C, Hoffbrand, AV. Combined therapy with deferiprone and desferrioxamine. Br J Haematol 1998; 103: 361–4.CrossRefGoogle ScholarPubMed
Ceci, A, Baiardi, P, Cataprano, M, et al. Risk factors for death in patients with β-thalassemia major: results of a case-control study. Haematologica 2006; 91: 1420–1.Google ScholarPubMed
Kontoghiorghes, GJ, Kolnagou, A. Effective new treatments of iron overload in thalassaemia using the ICOC combination therapy protocol of deferiprone (L1) and deferoxamine and of new chelating drugs. Haematologica 2006; 91: ELT04.Google ScholarPubMed
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: 858–63.CrossRefGoogle ScholarPubMed
Kearney, SL, Nemeth, E, Neufeld, EJ, et al. Urinary hepcidin in congenital chronic anemias. Pediatr Blood Cancer 2007; 48: 57–63.CrossRefGoogle ScholarPubMed
Barton, JC, Lee, PL, Bertoli, LF, Beutler, E. Iron overload in an African-American woman with SS hemoglobinopathy and a promoter mutation in the X-linked erythroid-specific 5-aminolevulinate synthase (ALAS2) gene. Blood Cells Mol Dis 2005; 34: 226–8.CrossRefGoogle Scholar
Lee, MT, Piomelli, S, Granger, S, et al. Stroke Prevention Trial in Sickle Cell Anemia (STOP): extended follow-up and final results. Blood 2006; 108: 8472.CrossRefGoogle ScholarPubMed
Treadwell, MJ, Law, AW, Sung, J, et al. Barriers to adherence of deferoxamine usage in sickle cell disease. Pediatr Blood Cancer 2005; 44: 500.CrossRefGoogle ScholarPubMed
Voskaridou, E, Douskou, M, Terpos, E, et al. Deferiprone as an oral iron chelator in sickle cell disease. Ann Hematol 2005; 84: 434–40.CrossRefGoogle ScholarPubMed
Okpala, I. Investigational agents for sickle cell disease. Expert Opin Investig Drugs 2006; 15: 833–42.CrossRefGoogle ScholarPubMed
Meo, A, Ruggeri, A, Rosa, MA, Zanghi, L, Morabito, N, Duca, L. Iron burden and liver fibrosis decrease during a long-term phlebotomy program and iron chelating treatment after bone marrow transplantation. Hemoglobin 2006; 30: 131.CrossRefGoogle ScholarPubMed
Porter, J, Ealanello, R, Saglio, E, et al. Relative response of patients with myelodysplastic syndromes and other transfusion-dependent anemias to deferasirox (ICL670): a 1-year prospective study. Eur J Hematol 2008; 80: 1686.Google Scholar
Gattermann, N. Clinical consequences of iron overload in myelodysplastic syndromes and treatment with chelators. Hematol/Oncol Clin 2006; 13–17.
Rose, C, Cambier, N, Mahieu, M, Ernst, O, Fenaux, P.[Iron overload and myelodysplastic syndromes.]Transfus Clin Biol 2001; 8: 422–32.CrossRefGoogle Scholar
Malcovati, L, Porta, MG, Pascutto, C, et al. Prognostic factors and life expectancy in myelodysplastic syndromes classified according to WHO criteria: a basis for clinical decision making. J Clin Oncol 2005; 23: 7594–603.CrossRefGoogle ScholarPubMed
Takatoku, M, Uchiyama, T, Okamoto, S, et al. Retrospective nationwide survey of Japanese patients with transfusion-dependent MDS and aplastic anemia highlights the negative impact of iron overload on morbidity/mortality. Eur J Haematol 2007; 78: 487–94.CrossRefGoogle Scholar
Armand, P, Kim, HT, Cutler, CS, et al. Prognostic impact of elevated pretransplantation serum ferritin in patients undergoing myeloablative stem cell transplantation. Blood 2007; 109: 4586–8.CrossRefGoogle ScholarPubMed
Maggio, A. Light and shadows in the iron chelation treatment of haematological diseases. Br J Haematol 2007; 138: 407–21.CrossRefGoogle ScholarPubMed
Steensma, DP. Myelodysplasia paranoia: iron as the new radon. Leuk Res 2009; 33: 1158–63.CrossRefGoogle ScholarPubMed
DeLoughery, TG.Iron: The fifth horseman of the apocalypse? Am J Hematol 2009; 84: 263–4.CrossRefGoogle ScholarPubMed
Gattermann, N, Cazzola, M, Greenberg, P, Maertens, J, Soulieres, D, Rose, C. The efficacy and tolerability of ICL670, a once-daily oral iron chelator, in patients with myelodysplastic syndromes (MDS) and iron overload. Leuk Res 2005; 29 (suppl 1): S76.CrossRefGoogle Scholar
Stone, RM.How, Itreat patients with myelodysplastic syndromes. Blood 2009; 113: 6296–303.CrossRefGoogle ScholarPubMed
Greenberg, PL, Baer, MR, Bennett, JM, et al. Myelodysplastic syndromes clinical practice guidelines in oncology. J Natl Compr Canc Netw 2006; 4: 587.Google Scholar
Greenberg, PL. Myelodysplastic syndromes: iron overload consequences and current chelating therapies. J Natl Compr Canc Netw 2006; 4: 91–6.CrossRefGoogle ScholarPubMed
Nielsen, P, Fischer, R, Buggisch, P, Janka-Schaub, G. Effective treatment of hereditary haemochromatosis with desferrioxamine in selected cases. Br J Haematol 2003; 123: 952–3.CrossRefGoogle ScholarPubMed
Barr, J, Berkovitch, M, Tavori, I, Kariv, N, Schejter, A, Eshel, G. Acute iron intoxication: the efficacy of deferiprone and sodium biocarbonate in the prevention of iron absorption from the digestive tract. Vet Hum Toxicol 1999; 41: 308–11.Google ScholarPubMed
Bacon, BR, Farahvash, MJ, Janney, CG, Neuschwander-Tetri, BA. Non-alcoholic steatohepatitis: an expanded clinical entity. Gastroenterology 1994; 107: 1103–9.CrossRefGoogle Scholar
Barton, JC, Felitti, VJ, Lee, P, Beutler, E. Characteristics of HFE C282Y homozygotes younger than age 30 years. Acta Haematol 2004; 112: 219–21.CrossRefGoogle ScholarPubMed
Adams, PC, Bradley, C, Frei, JV. Hepatic zinc in hemochromatosis. Clin Invest Med 1991; 14: 16–20.Google ScholarPubMed
Fabio, G, Minonzio, F, Delbini, P, Bianchi, A, Cappellini, MD. Reversal of cardiac complications by deferiprone and deferoxamine combination therapy in a patient affected by a severe type of juvenile hemochromatosis (JH). Blood 2007; 109: 362–4.CrossRefGoogle Scholar
Gordeuk, V, Mukiibi, J, Hasstedt, SJ, et al. Iron overload in Africa. Interaction between a gene and dietary iron content. N Engl J Med 1992; 326: 95–100.CrossRefGoogle ScholarPubMed
Barton, JC, Acton, RT, Rivers, CA, et al. Genotypic and phenotypic heterogeneity of African-Americans with primary iron overload. Blood Cells Mol Dis 2003; 31: 310–19.CrossRefGoogle ScholarPubMed
Speight, AN, Cliff, J. Iron storage disease of the liver in Dar es Salaam: a preliminary report on venesection therapy. East Afr Med J 1974; 51: 895–902.Google Scholar
Barton, JC, Lee, PL, West, C, Bottomley, SS.Iron overload and prolonged ingestion of iron supplements: Clinical features and mutation analysis of hemochromatosis-associated genes in four cases. Am J Hematol 2006; 81: 760.CrossRefGoogle ScholarPubMed
Alarcon, PA, Donovan, ME, Forbes, GB, Landaw, SA, Stockman, JA. Iron absorption in the thalassemia syndromes and its inhibition by tea. N Engl J Med 1979; 300: 5–8.CrossRefGoogle ScholarPubMed
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: 69904.CrossRefGoogle ScholarPubMed
Barton, JC, Bertoli, LF. Zinc gluconate lozenges for treating the common cold. Ann Intern Med 1997; 126: 738–9.CrossRefGoogle ScholarPubMed
Barton, JC, Patton, MA, Edwards, CQ, et al. Blood lead concentrations in hereditary hemochromatosis. J Lab Clin Med 1994; 124: 193–8.Google ScholarPubMed
Tallkvist, J, Bowlus, CL, Lonnerdal, B. DMT1 gene expression and cadmium absorption in human absorptive enterocytes. Toxicol Lett 2001; 122: 171.CrossRefGoogle ScholarPubMed
Akesson, A, Stal, P, Vahter, M. Phlebotomy increases cadmium uptake in hemochromatosis. Environ Health Perspect 2000; 108: 289–91.CrossRefGoogle ScholarPubMed
Barton, JC, Acton, RT. Hemochromatosis and Vibrio vulnificus wound Infections. J Clin Gastroenterol 2009; 43: 890–3.
Walshe, JM, Cox, DW. Effect of treatment of Wilson's disease on natural history of haemochromatosis. Lancet 1998; 352: 112–13.CrossRefGoogle ScholarPubMed
Shiono, Y, Wakusawa, S, Hayashi, H, et al. Iron accumulation in the liver of male patients with Wilson's disease. Am J Gastroenterol 2001; 96: 31471.CrossRefGoogle ScholarPubMed
Camaschella, C. Understanding iron homeostasis through genetic analysis of hemochromatosis and related disorders. Blood 2005; 106: 3710–17.CrossRefGoogle ScholarPubMed
Speight, AN, Cliff, J. Iron storage disease of the liver in Dar es Salaam: a preliminary report on venesection therapy. East Afr Med J 1974; 51: 895–902.Google Scholar
Barton, JC, Edwards, CQ, Bertoli, LF, Shroyer, TW, Hudson, SL. Iron overload in African-Americans. Am J Med 1995; 99: 616–23.CrossRefGoogle ScholarPubMed
Wurapa, RK, Gordeuk, VR, Brittenham, GM, Khiyami, A, Schechter, GP, Edwards, CQ. Primary iron overload in African-Americans. Am J Med 1996; 101: 9–18.CrossRefGoogle ScholarPubMed
Barton, JC, Acton, RT. Inheritance of two HFE mutations in African-Americans: cases with hemochromatosis phenotypes and estimates of hemochromatosis phenotype frequency. Genet Med 2001; 3: 294–300.CrossRefGoogle ScholarPubMed
Lundvall, O. Phlebotomy treatment of porphyria cutanea tarda. Acta Derm Venereol Suppl (Stockh) 1982; 100: 107–18.Google ScholarPubMed
Chrobak, L. Successful treatment of iron overload with phlebotomies in two siblings with congenital dyserythropoietic anemia-type II (CDA-II). Acta Medica (Hradec Kralove) 2006; 49: 193.Google Scholar
Hofmann, WK, Kaltwasser, JP, Hoelzer, D, Nielsen, P, Gabbe, EE. Successful treatment of iron overload by phlebotomies in a patient with severe congenital dyserythropoietic anemia type II. Blood 1997; 89: 3068–9.Google Scholar
Lee, PL, Barton, JC, Rao, SV, Acton, RT, Adler, BK, Beutler, E. Three kinships with ALAS2 P520L (c.1559 C→T) mutation, two in association with severe iron overload, and one with sideroblastic anemia and severe iron overload. Blood Cells Mol Dis 2006; 36: 292.CrossRefGoogle Scholar
Zimelman, AP, Miller, A. Primary hemochromatosis with hereditary spherocytosis. Arch Intern Med 1980; 140: 983–4.CrossRefGoogle ScholarPubMed
Valenti, L, Fracanzani, AL, Dongiovanni, P, et al. Iron depletion by phlebotomy improves insulin resistance in patients with nonalcoholic fatty liver disease and hyperferritinemia: evidence from a case-control study. Am J Gastroenterol 2007; 102: 1251–8.CrossRefGoogle ScholarPubMed
Hayashi, H, Takikawa, T, Nishimura, N, Yano, M, Isomura, T, Sakamoto, N. Improvement of serum aminotransferase levels after phlebotomy in patients with chronic active hepatitis C and excess hepatic iron. Am J Gastroenterol 1994; 89: 986–8.Google Scholar
Piperno, A, Sampietro, M, D'Alba, R, et al. Iron stores, response to alpha-interferon therapy, and effects of iron depletion in chronic hepatitis C. Liver 1996; 16: 2484.CrossRefGoogle ScholarPubMed
Guillygomarc'h, A, Mendler, MH, Moirand, R, et al. Venesection therapy of insulin resistance-associated hepatic iron overload. J Hepatol 2001; 35: 344–9.CrossRefGoogle ScholarPubMed
Hramiak, IM, Finegood, DT, Adams, PC. Factors affecting glucose tolerance in hereditary hemochromatosis. Clin Invest Med 1997; 20: 110–18.Google ScholarPubMed
Piperno, A, Vergani, A, Salvioni, A, et al. Effects of venesections and restricted diet in patients with the insulin-resistance hepatic iron overload syndrome. Liver Int 2004; 24: 471–6.CrossRefGoogle ScholarPubMed
Nick, H, Acklin, P, Lattmann, R, et al. Development of tridentate iron chelators: from desferrithiocin to ICL670. Curr Med Chem 2003; 10: 10656.CrossRefGoogle ScholarPubMed

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