How I treat hemochromatosis.

Hemochromatosis is a common genetic disorder in which iron may progressively accumulate in the liver, heart, and other organs. The primary goal of therapy is iron depletion to normalize body iron stores and to prevent or decrease organ dysfunction. The primary therapy to normalize iron stores is phlebotomy. In this opinion article, we discuss the indications for and monitoring of phlebotomy therapy to achieve iron depletion, maintenance therapy, dietary and pharmacologic maneuvers that could reduce iron absorption, and the role of voluntary blood donation.

[1]  D. English,et al.  HFE C282Y homozygotes are at increased risk of breast and colorectal cancer , 2010, Hepatology.

[2]  K. Kowdley,et al.  The role of iron in the pathophysiology and treatment of chronic hepatitis C. , 2009, Canadian journal of gastroenterology = Journal canadien de gastroenterologie.

[3]  H. Bonkovsky,et al.  A Phase I/II, Open-Label, Dose-Escalation Trial of Once-Daily Oral Chelator Deferasirox to Treat Iron Overload in HFE-Related Hereditary Hemochromatosis: Final Results of the Core Study. , 2009 .

[4]  V. Sachdev,et al.  Does Oxidative Stress Modulate Left Ventricular Diastolic Function in Asymptomatic Subjects with Hereditary Hemochromatosis? , 2009, Echocardiography.

[5]  P. Adams The Natural History of Untreated HFE-Related Hemochromatosis , 2009, Acta Haematologica.

[6]  J. Barton,et al.  Hemochromatosis and Vibrio vulnificus Wound Infections , 2009, Journal of clinical gastroenterology.

[7]  G. Anderson,et al.  Hepcidin regulation in wild-type and Hfe knockout mice in response to alcohol consumption: evidence for an alcohol-induced hypoxic response. , 2009, Alcoholism, clinical and experimental research.

[8]  V. Subramaniam,et al.  Co-factors in liver disease: the role of HFE-related hereditary hemochromatosis and iron. , 2009, Biochimica et biophysica acta.

[9]  C. Camaschella BMP6 orchestrates iron metabolism , 2009, Nature Genetics.

[10]  D. English,et al.  The natural history of serum iron indices for HFE C282Y homozygosity associated with hereditary hemochromatosis. , 2008, Gastroenterology.

[11]  P. Adams Natural history of hemochromatosis: heading down the up escalator? , 2008, Gastroenterology.

[12]  J. Pankow,et al.  HFE C282Y homozygotes have reduced low-density lipoprotein cholesterol: the Atherosclerosis Risk in Communities (ARIC) Study. , 2008, Translational research : the journal of laboratory and clinical medicine.

[13]  M. Knuiman,et al.  Noncitrus fruits as novel dietary environmental modifiers of iron stores in people with or without HFE gene mutations. , 2008, Mayo Clinic proceedings.

[14]  J. Barton Ferritin >1000: grand for hemochromatosis screening? , 2008 .

[15]  R. Williamson,et al.  Asymptomatic individuals at genetic risk of haemochromatosis take appropriate steps to prevent disease related to iron overload , 2008, Liver international : official journal of the International Association for the Study of the Liver.

[16]  V. de Lédinghen,et al.  Diagnosis of liver fibrosis using FibroScan and other noninvasive methods in patients with hemochromatosis: a prospective study. , 2008, Gastroenterologie clinique et biologique.

[17]  D. English,et al.  Iron-overload-related disease in HFE hereditary hemochromatosis. , 2008, The New England journal of medicine.

[18]  D. Girelli,et al.  Blunted hepcidin response to oral iron challenge in HFE-related hemochromatosis. , 2007, Blood.

[19]  G. Koek,et al.  Therapeutic erythrocytapheresis versus phlebotomy in the initial treatment of hereditary hemochromatosis - A pilot study. , 2007, Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis.

[20]  L. Régent [Management of hemochromatosis]. , 2007, Soins; la revue de reference infirmiere.

[21]  J. Powell,et al.  Proton pump inhibitors suppress absorption of dietary non-haem iron in hereditary haemochromatosis , 2007, Gut.

[22]  J. Barton Chelation therapy for iron overload , 2007, Nutrition reviews.

[23]  Y. Kohgo,et al.  Hepcidin is down-regulated in alcohol loading. , 2007, Alcoholism, clinical and experimental research.

[24]  J. Barton,et al.  Iron overload and prolonged ingestion of iron supplements: Clinical features and mutation analysis of hemochromatosis‐associated genes in four cases , 2006, American journal of hematology.

[25]  A. Tavill,et al.  A diagnostic approach to hemochromatosis. , 2006, Canadian journal of gastroenterology = Journal canadien de gastroenterologie.

[26]  P. Brissot,et al.  Reversibility of hepatic fibrosis in treated genetic hemochromatosis: A study of 36 cases , 2006, Hepatology.

[27]  D. Hewett,et al.  Screening for hemochromatosis in asymptomatic subjects with or without a family history. , 2006, Archives of internal medicine.

[28]  D. Greenwood,et al.  HFE Genotype Modifies the Influence of Heme Iron Intake on Iron Status , 2005, Epidemiology.

[29]  W. Sly,et al.  Pathophysiology of hereditary hemochromatosis. , 2005, Seminars in liver disease.

[30]  D. Greenwood,et al.  Diet and genetic factors associated with iron status in middle-aged women. , 2005, The American journal of clinical nutrition.

[31]  M. Pouchard,et al.  Redox active plasma iron in C282Y/C282Y hemochromatosis. , 2005, Blood.

[32]  N. Andrews,et al.  Slc11a2 is required for intestinal iron absorption and erythropoiesis but dispensable in placenta and liver. , 2005, The Journal of clinical investigation.

[33]  E. Thomson,et al.  Hemochromatosis and iron-overload screening in a racially diverse population. , 2005, The New England journal of medicine.

[34]  B. Newman Hemochromatosis blood donor programs: marginal for the red blood cell supply but potentially good for patient care , 2004, Transfusion.

[35]  T. Power,et al.  Hemochromatosis patients as voluntary blood donors. , 2004, Canadian journal of gastroenterology = Journal canadien de gastroenterologie.

[36]  B. Nordestgaard,et al.  Hemochromatosis mutations in the general population: iron overload progression rate. , 2004, Blood.

[37]  P. Buggisch,et al.  Effective treatment of hereditary haemochromatosis with desferrioxamine in selected cases , 2003, British journal of haematology.

[38]  J. Barton,et al.  Phlebotomy-Mobilized Iron as a Surrogate for Liver Iron Content in Hemochromatosis Patients , 2003, Hematology.

[39]  H. Klein,et al.  Hemochromatosis subjects as allogeneic blood donors: a prospective study , 2003, Transfusion.

[40]  C. Yamashita,et al.  Natural history of the C282Y homozygote for the hemochromatosis gene (HFE) with a normal serum ferritin level. , 2003, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[41]  V. Felitti,et al.  Prevalence of hemochromatosis-related symptoms among individuals with mutations in the HFE gene. , 2002, Mayo Clinic proceedings.

[42]  V. Felitti,et al.  The C282Y mutation does not shorten life span. , 2002, Archives of internal medicine.

[43]  M. Speechley,et al.  Natural history of C282Y homozygotes for hemochromatosis. , 2002, Canadian journal of gastroenterology = Journal canadien de gastroenterologie.

[44]  R. Hider Nature of nontransferrin‐bound iron , 2002, European journal of clinical investigation.

[45]  K. Hveem,et al.  Persons with Screening-detected Haemochromatosis: as Healthy as the General Population? , 2002, Scandinavian journal of gastroenterology.

[46]  F. Courtois,et al.  [Genetic hemochromatosis and blood donation]. , 2001, Annales de medecine interne.

[47]  K. Hveem,et al.  Screening for Hemochromatosis: High Prevalence and Low Morbidity in an Unselected Population of 65,238 Persons , 2001, Scandinavian journal of gastroenterology.

[48]  S. Glynn,et al.  Prevalence, donation practices, and risk assessment of blood donors with hemochromatosis. , 2001, JAMA.

[49]  T. Rouault,et al.  MCV as a guide to phlebotomy therapyfor hemochromatosis , 2001, Transfusion.

[50]  J. Barton,et al.  Iron deficiency due to excessive therapeutic phlebotomy in hemochromatosis , 2000, American journal of hematology.

[51]  C. Seamark,et al.  Should asymptomatic haemochromatosis be treated?Treatment can be onerous for patient and doctorCommentary: False certainty of clinical guidanceCommentary: Early treatment is essential , 2000, BMJ : British Medical Journal.

[52]  C. Seamark,et al.  Should asymptomatic haemochromatosis be treated?Treatment can be onerous for patient and doctorCommentary: False certainty of clinical guidanceCommentary: Early treatment is essential , 2000 .

[53]  C. Bollard,et al.  Blood donation by healthy individuals with haemochromatosis. , 2000, The New Zealand medical journal.

[54]  J. Olynyk,et al.  A population-based study of the clinical expression of the hemochromatosis gene. , 1999, The New England journal of medicine.

[55]  A. Grindon,et al.  Hemochromatosis probands as blood donors , 1999, Transfusion.

[56]  R. Yip,et al.  A survey of 2,851 patients with hemochromatosis: symptoms and response to treatment. , 1999, The American journal of medicine.

[57]  A. Grindon,et al.  A survey of phlebotomy among persons with hemochromatosis , 1999, Transfusion.

[58]  J. Cook,et al.  Management of hemochromatosis. Hemochromatosis Management Working Group. , 1998, Annals of internal medicine.

[59]  R. Gottschalk,et al.  Clinical trial on the effect of regular tea drinking on iron accumulation in genetic haemochromatosis , 1998, Gut.

[60]  P. Adams Factors affecting the rate of iron mobilization during venesection therapy for genetic hemochromatosis , 1998, American journal of hematology.

[61]  H. Schumacher Arthropathy in hemochromatosis. , 1998, Hospital practice.

[62]  B. Bacon,et al.  Hepatic Iron Concentration in Hereditary Hemochromatosis Does Not Saturate or Accurately Predict Phlebotomy Requirements , 1998, American Journal of Gastroenterology.

[63]  Å. Bruce,et al.  The effect of withdrawal of food iron fortification in Sweden as studied with phlebotomy in subjects with genetic hemochromatosis , 1997, European Journal of Clinical Nutrition.

[64]  Stephan Nussberger,et al.  Cloning and characterization of a mammalian proton-coupled metal-ion transporter , 1997, Nature.

[65]  D. Häussinger,et al.  Long-term survival in patients with hereditary hemochromatosis. , 1996, Gastroenterology.

[66]  W. Crosby,et al.  Hereditary hemochromatosis. , 1993, Journal of the American Medical Association (JAMA).

[67]  M. Pippard,et al.  Iron Metabolism in Health and Disease , 1994 .

[68]  C. Friedrich Blood donation by patients with hemochromatosis. , 1993, JAMA.

[69]  H. L. Penning Blood donation by patients with hemochromatosis. , 1993, JAMA.

[70]  P. Adams,et al.  Rate of iron reaccumulation following iron depletion in hereditary hemochromatosis. Implications for venesection therapy. , 1993, Journal of clinical gastroenterology.

[71]  M. Worwood,et al.  Serum ferritin, blood donation, iron stores and haemochromatosis , 1993, Transfusion medicine.

[72]  W. Zoller,et al.  Repeated isovolemic large-volume erythrocytapheresis in the treatment of idiopathic hemochromatosis. , 1992, Zeitschrift fur Gastroenterologie.

[73]  M. Speechley,et al.  Long-term survival analysis in hereditary hemochromatosis. , 1991, Gastroenterology.

[74]  M. Nathanson,et al.  Regulation of intestinal iron absorption and mucosal iron kinetics in hereditary hemochromatosis. , 1991, The Journal of laboratory and clinical medicine.

[75]  N. N. Brown,et al.  Factors affecting the concentrations of ferritin in serum in a healthy Australian population. , 1990, Clinical chemistry.

[76]  B. Bacon,et al.  The pathology of hepatic iron overload: A free radical‐Mediated Process? , 1990, Hepatology.

[77]  J. Cook,et al.  Food iron absorption in idiopathic hemochromatosis. , 1989, Blood.

[78]  D. Conte,et al.  Effectiveness of Erythrocytapheresis in Idiopathic Hemochromatosis. Report of 14 Cases , 1989, The International journal of artificial organs.

[79]  B. Bannwarth,et al.  Haematological Adverse Effects of Histamine H2-Receptor Antagonists , 1988, Medical toxicology and adverse drug experience.

[80]  O. Aruoma,et al.  Nontransferrin-bound iron in plasma from hemochromatosis patients: effect of phlebotomy therapy. , 1988, Blood.

[81]  K. S. Olsson,et al.  The Effect of Iron Fortification of the Diet on Clinical Iron Overload in the General Population , 1988, Annals of the New York Academy of Sciences.

[82]  M. Skolnick,et al.  Prevalence of hemochromatosis among 11,065 presumably healthy blood donors. , 1988, The New England journal of medicine.

[83]  W. Crosby Hemochromatosis. Treatment to alleviate injury. , 1986, Archives of internal medicine.

[84]  B. Halliwell,et al.  Low-molecular-weight iron complexes and oxygen radical reactions in idiopathic haemochromatosis. , 1985, Clinical science.

[85]  E. Henze,et al.  Primary hemochromatosis: anatomic and physiologic characteristics of the cardiac ventricles and their response to phlebotomy. , 1984, The American journal of cardiology.

[86]  W. Bezwoda,et al.  Effect of diet on the rate of iron accumulation in idiopathic haemochromatosis. , 1981, South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde.

[87]  E. Rachmilewitz,et al.  Non‐Specific Serum Iron in Thalassaemia: an Abnormal Serum Iron Fraction of Potential Toxicity , 1978, British journal of haematology.

[88]  L. Powell THE ROLE OF ALCOHOLISM IN HEPATIC IRON STORAGE DISEASE * , 1975, Annals of the New York Academy of Sciences.

[89]  J. Cook,et al.  Iron fortification of food: its measurement by the extrinsic tag method. , 1973, Blood.

[90]  J. Stockman Iron-Overload–Related Disease in HFE Hereditary Hemochromatosis , 2009 .

[91]  E. Beutler,et al.  Effects of alcohol consumption on iron metabolism in mice with hemochromatosis mutations. , 2007, Alcoholism, clinical and experimental research.

[92]  M. Cappellini,et al.  Reversal of cardiac complications by deferiprone and deferoxamine combination therapy in a patient affected by a severe type of juvenile hemochromatosis (JH). , 2007, Blood.

[93]  D. van der A,et al.  HFE genotypes and dietary heme iron: no evidence of strong gene-nutrient interaction on serum ferritin concentrations in middle-aged women. , 2006, Nutrition, metabolism, and cardiovascular diseases : NMCD.

[94]  A. Piperno,et al.  Erythrocytapheresis plus erythropoietin: an alternative therapy for selected patients with hemochromatosis and severe organ damage. , 2005, Haematologica.

[95]  P. Brissot,et al.  Role of non-transferrin-bound iron in the pathogenesis of iron overload and toxicity. , 2002, Advances in experimental medicine and biology.

[96]  P. Adams,et al.  Eligibility and exclusion of hemochromatosis patients as voluntary blood donors. , 1998, Canadian journal of gastroenterology = Journal canadien de gastroenterologie.

[97]  W. Crosby A history of phlebotomy therapy for hemochromatosis. , 1991, The American journal of the medical sciences.

[98]  J. H. Jandl Blood : textbook of hematology , 1987 .

[99]  A. Walan,et al.  Metabolic consequences of reduced gastric acidity. , 1985, Scandinavian journal of gastroenterology. Supplement.

[100]  H. Koornhof,et al.  Generalized infection with Yersinia enterocolitica and the role of iron. , 1979, Contributions to microbiology and immunology.

[101]  W. Bezwoda,et al.  Can iron fortification of flour cause damage to genetic susceptibles (idiopathic haemochromatosis and beta-thalassaemia major)? , 1978, Human genetics. Supplement.