Transfusion-Induced Iron Overload Treatment & Management

  • Author: Muhammad A Mir, MBBS, FACP; Chief Editor: Emmanuel C Besa, MD   more...
 
Updated: Mar 23, 2012
 

Medical Care

Unlike patients with primary hemochromatosis and some other causes of secondary iron overload, patients with transfusion-induced iron overload are already anemic, and therapeutic phlebotomy is not usually an option, with the exception of curable disorders such as leukemia that is in complete remission.[73]

The primary goal of iron chelation therapy is to prevent the accumulation of iron reaching harmful levels by matching iron intake from blood transfusion, with iron excreted by iron chelation.[74] Although NTBI and liver deposits are chelatable to a degree, iron that is deposited in other organs such as the heart is not readily chelated, making cardiac failure a leading cause of death amongst those who undergo long-term transfusions.[75]

The initiation of chelation therapy is a decision that has to be individualized. In general, transfusions exceeding 100 mL/kg of body weight are reasonable enough to merit thorough evaluation and probable initiation. Autopsy studies in the 1970s[76] and MRI data[77] obtained in recent years show that after 75 or more units of transfused blood, more than 50% of patients have excess iron in their myocardium.

Deferoxamine  (DFO) has been used for over 30 years for iron chelation. However, it is a parenteral drug that requires subcutaneous or intravenous infusions, owing to its short half-life and poor oral bioavailability, making compliance an issue.[78]

The only randomized trial comparing chelation with intramuscular deferoxamine to no chelation was small and presented 20 children with thalassemia. At about 6 years, the mean hepatic iron concentration mg/g of liver tissue was 42 in the untreated group and 26 in the deferoxamine group.[79] At 14 years, 6 deaths occurred in the untreated group, versus 1 in the treated group.[80] The early use of deferoxamine in an amount proportional to the transfusional iron load reduces the body iron burden and helps protect against diabetes mellitus, cardiac disease, and early death in patients with thalassemia major.[81] In the United States, the mean total medical costs have been estimated to be $59,233 per year, including $10,899 for deferoxamine and $8,722 for the administration of chelation therapy.[82]

Two novel oral iron chelators, deferiprone and deferasirox (EXJADE; Novartis Pharma Stein AG, Stein, Switzerland), provide potentially useful treatments for iron overload. A new enthusiastic era for iron chelation with less burdensome oral treatments is dawning, but long-term follow-up is required before pumps and needles can be thrown away.[83]

Deferiprone  (Ferriprox) has been at the center stage of a huge controversy between the major investigator (Dr. Nancy Olivieri, the Hospital for Sick Children and the University of Toronto) and the drug manufacturer ApoPharma .[84] The original study, after 7 years of research, concluded that deferiprone was less effective and resulted in an increased incidence of hepatic fibrosis.[85] Although some conflicting data exist from larger studies,[86] the drug did not gain approval in Canada, but it was approved in Europe and is also being manufactured in India.

Deferiprone was approved the US Food and Drug Administration in October 2011. Approval was based on serum ferritin level reduction; no controlled trials demonstrated a direct treatment benefit (eg, improvement in disease-related symptoms, functioning, or increased survival). At least one study has reported improved cardiac outcomes with deferiprone,[87] which, if true, is a major advantage of this drug, as cardiac failure remains the top killer in thalassemia patients.

Deferasirox  (EXJADE) is preferred by patients due to its convenient once-daily oral administration[88] and its cost-effectiveness.[89] Deferasirox has been approved by the United States Food and Drug Administration (FDA). This agent has an acceptable tolerability profile and appears to have similar efficacy to deferoxamine in reducing the iron burden in transfused patients with sickle cell disease.[90]

In a comparative study of β-thalassemia patients, noninferiority was demonstrated in the group of patients who were allocated to the higher dose groups (deferasirox doses of 20 or 30 mg/kg) for baseline liver iron concentrations (LIC) of 7 mg/g dry weight or greater when compared with deferoxamine.[91] In another study, deferasirox 20 mg/kg showed similar efficacy to deferoxamine 40 mg/kg in terms of decreases in LIC.[92]

In a phase III study of 586 children with thalassemia that compared deferasirox with deferoxamine at 1 year, 53% of children in the deferasirox group had maintained or reduced hepatic iron concentrations, versus 66% in the deferoxamine group.[93]

A Cochrane database review by Meerpohl et al of 4 clinical trials (including 2 comparing deferasirox with deferoxamine) concluded that the drugs have similar efficacy and short-term safety profiles. However, the review fell short of recommending deferasirox as first-line treatment, despite patients preferring it over cumbersome deferoxamine administration in patients with thalassemia and transfusional iron overload.[94]

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Surgical Care

Liver and cardiac transplantation should be considered for appropriate patients with end-stage disease. Combined liver-heart transplants have been carried out successfully in thalassemia patients.[95]

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Consultations

Consultations with the following specialists should be sought in cases of transfusion-induced iron overload:

  • Hematologist
  • Cardiologist
  • Gastroenterologist/Hepatologist
  • Endocrinologist
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Diet

Ascorbic acid (vitamin C) increases the absorption of iron 2.9-3.5 times the normal amount[96] and should probably be avoided, along with alcohol and, of course, iron supplements.

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Activity

Activity in patients with transfusion-induced iron overload is as tolerated.

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Proceed to Medication
 
 
Contributor Information and Disclosures
Author

Muhammad A Mir, MBBS, FACP  Attending Physician, Department of Medicine, Eastern Maine Medical Center

Muhammad A Mir, MBBS, FACP is a member of the following medical societies: American College of Physicians and American Society of Hematology

Disclosure: Nothing to disclose.

Coauthor(s)

Gerald L Logue, MD  Professor of Medicine, Head of the Division of Hematology, Vice Chairman for Education, Department of Medicine, University of Buffalo State University of New York School of Medicine and Biomedical Sciences

Gerald L Logue, MD is a member of the following medical societies: Alpha Omega Alpha, American Association for the Advancement of Science, American College of Physicians, American Federation for Clinical Research, and American Society of Hematology

Disclosure: Nothing to disclose.

Specialty Editor Board

Pradyumna D Phatak, MBBS, MD  Chair, Division of Hematology and Medical Oncology, Rochester General Hospital; Clinical Professor of Oncology, Roswell Park Cancer Institute

Pradyumna D Phatak, MBBS, MD, is a member of the following medical societies: American Society of Hematology

Disclosure: Novartis Honoraria Speaking and teaching

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Ronald A Sacher, MB, BCh, MD, FRCPC  Professor, Internal Medicine and Pathology, Director, Hoxworth Blood Center, University of Cincinnati Academic Health Center

Ronald A Sacher, MB, BCh, MD, FRCPC is a member of the following medical societies: American Association for the Advancement of Science, American Association of Blood Banks, American Clinical and Climatological Association, American Society for Clinical Pathology, American Society of Hematology, College of American Pathologists, International Society of Blood Transfusion, International Society on Thrombosis and Haemostasis, and Royal College of Physicians and Surgeons of Canada

Disclosure: Glaxo Smith Kline Honoraria Speaking and teaching; Talecris Honoraria Board membership

Rajalaxmi McKenna, MD, FACP  Southwest Medical Consultants, SC, Department of Medicine, Good Samaritan Hospital, Advocate Health Systems

Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis

Disclosure: Nothing to disclose.

Chief Editor

Emmanuel C Besa, MD  Professor, Department of Medicine, Division of Hematologic Malignancies, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University

Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Clinical Oncology, American Society of Hematology, and New York Academy of Sciences

Disclosure: Nothing to disclose.

References

  1. Anderson GJ. Mechanisms of iron loading and toxicity. Am J Hematol. Dec 2007;82(12 suppl):1128-31. [Medline].

  2. Anderson GJ, Vulpe CD. Regulation of intestinal iron transport. In: Templeton DM, ed. Molecular and Cellular Iron Transport. New York: Marcel Dekker Inc; 2002:559-96.

  3. Diseases of iron metabolism. The Internet Pathology Laboratory for Medical Education. Available at http://library.med.utah.edu/WebPath/TUTORIAL/IRON/IRON.html. Accessed December 16, 2007.

  4. Pietrangelo A. Hereditary hemochromatosis. Biochim Biophys Acta. Jul 2006;1763(7):700-10. [Medline].

  5. Anderson GJ, Darshan D, Wilkins SJ, Frazer DM. Regulation of systemic iron homeostasis: how the body responds to changes in iron demand. Biometals. Jun 2007;20(3-4):665-74. [Medline].

  6. Anderson GJ. Mechanisms of iron loading and toxicity. Am J Hematol. Dec 2007;82(12 suppl):1128-31. [Medline].

  7. Hershko C. Iron loading and its clinical implications. Am J Hematol. Dec 2007;82(12 suppl):1147-8. [Medline].

  8. Origa R, Galanello R, Ganz T, et al. Liver iron concentrations and urinary hepcidin in beta-thalassemia. Haematologica. May 2007;92(5):583-8. [Medline]. [Full Text].

  9. Kohgo Y, Ohtake T, Ikuta K, et al. Iron accumulation in alcoholic liver diseases. Alcohol Clin Exp Res. Nov 2005;29(11 suppl):189S-93S. [Medline].

  10. Esposito BP, Breuer W, Sirankapracha P, et al. Labile plasma iron in iron overload: redox activity and susceptibility to chelation. Blood. Oct 1 2003;102(7):2670-7. [Medline]. [Full Text].

  11. Gutteridge JM. Lipid peroxidation and antioxidants as biomarkers of tissue damage. Clin Chem. Dec 1995;41(12 pt 2):1819-28. [Medline]. [Full Text].

  12. Ganong WF. Digestion and absorption. In: Ganong WF, ed. Review of Medical Physiology. 17th ed. East Norwalk, Conn, U: Appleton & Lange; 1995:441.

  13. Bowen R. Ferritin and hemosiderin. Updated April 7, 2001. Hypertexts for Biomedical Sciences. Available at http://www.vivo.colostate.edu/hbooks/molecules/ferritin.html. Accessed December 23, 2007.

  14. Olivieri NF, Nathan DG, MacMillan JH, et al. Survival in medically treated patients with homozygous beta-thalassemia. N Engl J Med. Sep 1 1994;331(9):574-8. [Medline]. [Full Text].

  15. Suarez WA, Snyder SA, Berman BB, Brittenham GM, Patel CR. Preclinical cardiac dysfunction in transfusion-dependent children and young adults detected with low-dose dobutamine stress echocardiography. J Am Soc Echocardiogr. Oct 1998;11(10):948-56. [Medline].

  16. Wolfe L, Olivieri N, Sallan D, et al. Prevention of cardiac disease by subcutaneous deferoxamine in patients with thalassemia major. N Engl J Med. Jun 20 1985;312(25):1600-3. [Medline].

  17. Huang YC, Chang JS, Wu KH, Peng CT. Regression of myocardial dysfunction after switching from desferrioxamine to deferiprone therapy in beta-thalassemia major patients. Hemoglobin. 2006;30(2):229-38. [Medline].

  18. Aessopos A, Farmakis D. Pulmonary hypertension in beta-thalassemia. Ann N Y Acad Sci. 2005;1054:342-9. [Medline].

  19. Piatti G, Allegra L, Fasano V, et al. Lung function in beta-thalassemia patients: a longitudinal study. Acta Haematol. 2006;116(1):25-9. [Medline].

  20. Jean G, Terzoli S, Mauri R, Borghetti L, Di Palma A, Piga A, et al. Cirrhosis associated with multiple transfusions in thalassaemia. Arch Dis Child. Jan 1984;59(1):67-70. [Medline]. [Full Text].

  21. Liuzzi JP, Aydemir F, Nam H, Knutson MD, Cousins RJ. Zip14 (Slc39a14) mediates non-transferrin-bound iron uptake into cells. Proc Natl Acad Sci U S A. Sep 12 2006;103(37):13612-7. [Medline]. [Full Text].

  22. Moayeri H, Oloomi Z. Prevalence of growth and puberty failure with respect to growth hormone and gonadotropins secretion in beta-thalassemia major. Arch Iran Med. Oct 2006;9(4):329-34. [Medline].

  23. Gamberini MR, Fortini M, De Sanctis V, Gilli G, Testa MR. Diabetes mellitus and impaired glucose tolerance in thalassaemia major: incidence, prevalence, risk factors and survival in patients followed in the Ferrara Center. Pediatr Endocrinol Rev. Dec 2004;2 suppl 2:285-91. [Medline].

  24. Angelopoulos NG, Zervas A, Livadas S, et al. Reduced insulin secretion in normoglycaemic patients with beta-thalassaemia major. Diabet Med. Dec 2006;23(12):1327-31. [Medline].

  25. De Sanctis V, Roos M, Gasser T, et al. Impact of long-term iron chelation therapy on growth and endocrine functions in thalassaemia. J Pediatr Endocrinol Metab. Apr 2006;19(4):471-80. [Medline].

  26. Cantinieaux B, Janssens A, Boelaert JR, et al. Ferritin-associated iron induces neutrophil dysfunction in hemosiderosis. J Lab Clin Med. Apr 1999;133(4):353-61. [Medline].

  27. Chirio R, Collignon A, Sabbah L, Lestradet H, Torlotin JC. [Yersinia enterocolitica infections and thalassemia major in children] [French]. Ann Pediatr (Paris). May 1989;36(5):308; 311-4. [Medline].

  28. Bergmann TK, Vinding K, Hey H. Multiple hepatic abscesses due to Yersinia enterocolitica infection secondary to primary haemochromatosis. Scand J Gastroenterol. Aug 2001;36(8):891-5. [Medline].

  29. Chiu HY, Flynn DM, Hoffbrand AV, Politis D. Infection with Yersinia enterocolitica in patients with iron overload. Br Med J (Clin Res Ed). Jan 11 1986;292(6513):97. [Medline].

  30. Karimi M, Jamalian N, Rasekhi A, Kashef S. Magnetic resonance imaging (MRI) findings of joints in young beta-thalassemia major patients: fluid surrounding the scaphoid bone: a novel finding, as the possible effect of secondary hemochromatosis. J Pediatr Hematol Oncol. Jun 2007;29(6):393-8. [Medline].

  31. Cunningham MJ, Macklin EA, Neufeld EJ, Cohen AR. Complications of beta-thalassemia major in North America. Blood. Jul 1 2004;104(1):34-9. [Medline]. [Full Text].

  32. Brittenham GM. Iron-chelating therapy for transfusional iron overload. N Engl J Med. Jan 13 2011;364(2):146-56. [Medline]. [Full Text].

  33. 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. Jun 2007;78(6):487-94. [Medline].

  34. Ladis V, Chouliaras G, Berdousi H, Kanavakis E, Kattamis C. Longitudinal study of survival and causes of death in patients with thalassemia major in Greece. Ann N Y Acad Sci. 2005;1054:445-50. [Medline].

  35. Fung EB, Harmatz P, Milet M, et al. Morbidity and mortality in chronically transfused subjects with thalassemia and sickle cell disease: A report from the multi-center study of iron overload. Am J Hematol. Apr 2007;82(4):255-65. [Medline].

  36. Brown KE, Khan CM, Zimmerman MB, Brunt EM. Hepatic iron overload in blacks and whites: a comparative autopsy study. Am J Gastroenterol. Jul 2003;98(7):1594-8. [Medline].

  37. Italian Working Group on Endocrine Complications in Non-endocrine Diseases. Multicentre study on prevalence of endocrine complications in thalassaemia major. Clin Endocrinol (Oxf). Jun 1995;42(6):581-6. [Medline].

  38. Milosevic R, Antonijevic N, Jankovic G, Babic D, Colovic M. [Aplastic anemia--clinical characteristics and survival analysis] [Serbian]. Srp Arh Celok Lek. Jul-Aug 1998;126(7-8):234-8. [Medline].

  39. Aul C, Gattermann N, Germing U, Runde V, Heyll A. [Myelodysplastic syndromes. The epidemiological and etiological aspects] [German]. Dtsch Med Wochenschr. Aug 14 1992;117(33):1223-31. [Medline].

  40. Hassan M, Hasan S, Giday S, et al. Hepatitis C virus in sickle cell disease. J Natl Med Assoc. Oct 2003;95(10):939-42. [Medline].

  41. Halonen P, Mattila J, Suominen P, et al. Iron overload in children who are treated for acute lymphoblastic leukemia estimated by liver siderosis and serum iron parameters. Pediatrics. Jan 2003;111(1):91-6. [Medline]. [Full Text].

  42. Files B, Brambilla D, Kutlar A, et al. Longitudinal changes in ferritin during chronic transfusion: a report from the Stroke Prevention Trial in Sickle Cell Anemia (STOP). J Pediatr Hematol Oncol. May 2002;24(4):284-90. [Medline].

  43. Borgna-Pignatti C, Castriota-Scanderbeg A. Methods for evaluating iron stores and efficacy of chelation in transfusional hemosiderosis. Haematologica. Sep-Oct 1991;76(5):409-13. [Medline].

  44. Kolnagou A, Economides C, Eracleous E, Kontoghiorghes GJ. Low serum ferritin levels are misleading for detecting cardiac iron overload and increase the risk of cardiomyopathy in thalassemia patients. The importance of cardiac iron overload monitoring using magnetic resonance imaging T2 and T2*. Hemoglobin. 2006;30(2):219-27. [Medline].

  45. Wood JC. Diagnosis and management of transfusion iron overload: the role of imaging. Am J Hematol. Dec 2007;82(12 suppl):1132-5. [Medline].

  46. Jacobs EM, Hendriks JC, van Tits BL, et al. 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. Jun 15 2005;341(2):241-50. [Medline].

  47. Pootrakul P, Breuer W, Sametband M, et al. Labile plasma iron (LPI) as an indicator of chelatable plasma redox activity in iron-overloaded beta-thalassemia/HbE patients treated with an oral chelator. Blood. Sep 1 2004;104(5):1504-10. [Medline]. [Full Text].

  48. Kemna EH, Tjalsma H, Podust VN, Swinkels DW. Mass spectrometry-based hepcidin measurements in serum and urine: analytical aspects and clinical implications. Clin Chem. Apr 2007;53(4):620-8. [Medline]. [Full Text].

  49. Guyader D, Gandon Y, Deugnier Y, et al. Evaluation of computed tomography in the assessment of liver iron overload. A study of 46 cases of idiopathic hemochromatosis. Gastroenterology. Sep 1989;97(3):737-43. [Medline].

  50. Howard JM, Ghent CN, Carey LS, Flanagan PR, Valberg LS. Diagnostic efficacy of hepatic computed tomography in the detection of body iron overload. Gastroenterology. Feb 1983;84(2):209-15. [Medline].

  51. Bell H, Rostad B, Raknerud N, Try K. [Computer tomography in the detection of hemochromatosis] [Norwegian]. Tidsskr Nor Laegeforen. Jun 10 1994;114(15):1697-9. [Medline].

  52. Sheth S. SQUID biosusceptometry in the measurement of hepatic iron. Pediatr Radiol. Jun 2003;33(6):373-7. [Medline].

  53. Nielsen P, Kordes U, Fischer R, Engelhardt R, Janka GE. [SQUID-biosusceptometry in iron overloaded patients with hematologic diseases] [German]. Klin Padiatr. Jul-Aug 2002;214(4):218-22. [Medline].

  54. Brittenham GM, Badman DG. Noninvasive measurement of iron: report of an NIDDK workshop. Blood. Jan 1 2003;101(1):15-9. [Medline]. [Full Text].

  55. Avrin WF, Kumar S. Noninvasive liver-iron measurements with a room-temperature susceptometer. Physiol Meas. Apr 2007;28(4):349-61. [Medline].

  56. Ghugre NR, Enriquez CM, Gonzalez I, et al. MRI detects myocardial iron in the human heart. Magn Reson Med. Sep 2006;56(3):681-6. [Medline].

  57. Westwood MA, Firmin DN, Gildo M, et al. Intercentre reproducibility of magnetic resonance T2* measurements of myocardial iron in thalassaemia. Int J Cardiovasc Imaging. Oct 2005;21(5):531-8. [Medline].

  58. Wood JC, Enriquez C, Ghugre N, Tyzka JM, Carson S, Nelson MD. MRI R2 and R2* mapping accurately estimates hepatic iron concentration in transfusion-dependent thalassemia and sickle cell disease patients. Blood. Aug 15 2005;106(4):1460-5. [Medline].

  59. Sparacia G, Midiri M, D'Angelo P, Lagalla R. Magnetic resonance imaging of the pituitary gland in patients with secondary hypogonadism due to transfusional hemochromatosis. MAGMA. May 1999;8(2):87-90. [Medline].

  60. Sparacia G, Iaia A, Banco A, D'Angelo P, Lagalla R. Transfusional hemochromatosis: quantitative relation of MR imaging pituitary signal intensity reduction to hypogonadotropic hypogonadism. Radiology. Jun 2000;215(3):818-23. [Medline]. [Full Text].

  61. Karimi M, Jamalian N, Rasekhi A, Kashef S. Magnetic resonance imaging (MRI) findings of joints in young beta-thalassemia major patients: fluid surrounding the scaphoid bone: a novel finding, as the possible effect of secondary hemochromatosis. J Pediatr Hematol Oncol. Jun 2007;29(6):393-8. [Medline].

  62. Papakonstantinou O, Ladis V, Kostaridou S, et al. The pancreas in beta-thalassemia major: MR imaging features and correlation with iron stores and glucose disturbances. Eur Radiol. Jun 2007;17(6):1535-43. [Medline].

  63. Wood JC, Enriquez C, Ghugre N, Tyzka JM, Carson S, Nelson MD, et al. MRI R2 and R2* mapping accurately estimates hepatic iron concentration in transfusion-dependent thalassemia and sickle cell disease patients. Blood. Aug 15 2005;106(4):1460-5. [Medline]. [Full Text].

  64. Gandon Y, Olivié D, Guyader D, et al. Non-invasive assessment of hepatic iron stores by MRI. Lancet. Jan 31 2004;363(9406):357-62. [Medline].

  65. Jensen PD, Heickendorff L, Carlson I, et al. Expression of CD2 and activation markers on blood T-helper cell subsets in patients with transfusional iron overload. Transfus Med. Feb 2001;11(1):21-30. [Medline].

  66. Angelucci E, Brittenham GM, McLaren CE, et al. Hepatic iron concentration and total body iron stores in thalassemia major. N Engl J Med. Aug 3 2000;343(5):327-31. [Medline]. [Full Text].

  67. Butensky E, Fischer R, Hudes M, et al. Variability in hepatic iron concentration in percutaneous needle biopsy specimens from patients with transfusional hemosiderosis. Am J Clin Pathol. Jan 2005;123(1):146-52. [Medline].

  68. Harmatz P, Butensky E, Quirolo K, et al. Severity of iron overload in patients with sickle cell disease receiving chronic red blood cell transfusion therapy. Blood. Jul 1 2000;96(1):76-9. [Medline]. [Full Text].

  69. Tobkes AI, Nord HJ. Liver biopsy: review of methodology and complications. Dig Dis. Sep-Oct 1995;13(5):267-74. [Medline].

  70. Fitchett DH, Coltart DJ, Littler WA, et al. Cardiac involvement in secondary haemochromatosis: a catheter biopsy study and analysis of myocardium. Cardiovasc Res. Dec 1980;14(12):719-24. [Medline].

  71. Thakerngpol K, Fucharoen S, Boonyaphipat P, et al. Liver injury due to iron overload in thalassemia: histopathologic and ultrastructural studies. Biometals. Apr 1996;9(2):177-83. [Medline].

  72. Telfer PT, Prestcott E, Holden S, et al. Hepatic iron concentration combined with long-term monitoring of serum ferritin to predict complications of iron overload in thalassaemia major. Br J Haematol. Sep 2000;110(4):971-7. [Medline].

  73. Franchini M, Gandini G, Veneri D, et al. Efficacy and safety of phlebotomy to reduce transfusional iron overload in adult, long-term survivors of acute leukemia. Transfusion. Jun 2004;44(6):833-7. [Medline].

  74. Porter JB. Concepts and goals in the management of transfusional iron overload. Am J Hematol. Dec 2007;82(12 suppl):1136-9. [Medline].

  75. Borgna-Pignatti C, Rugolotto S, De Stefano P, et al. Survival and complications in patients with thalassemia major treated with transfusion and deferoxamine. Haematologica. Oct 2004;89(10):1187-93. [Medline]. [Full Text].

  76. Buja LM, Roberts WC. Iron in the heart. Etiology and clinical significance. Am J Med. Aug 1971;51(2):209-21. [Medline].

  77. Jensen PD, Jensen FT, Christensen T, et al. Evaluation of myocardial iron by magnetic resonance imaging during iron chelation therapy with deferrioxamine: indication of close relation between myocardial iron content and chelatable iron pool. Blood. Jun 1 2003;101(11):4632-9. [Medline]. [Full Text].

  78. Cappellini MD, Bejaoui M, Agaoglu L, et al. Prospective evaluation of patient-reported outcomes during treatment with deferasirox or deferoxamine for iron overload in patients with beta-thalassemia. Clin Ther. May 2007;29(5):909-17. [Medline].

  79. Barry M, Flynn DM, Letsky EA, Risdon RA. Long-term chelation therapy in thalassaemia major: effect on liver iron concentration, liver histology, and clinical progress. Br Med J. Apr 6 1974;2(5909):16-20. [Medline]. [Full Text].

  80. Modell B, Letsky EA, Flynn DM, Peto R, Weatherall DJ. Survival and desferrioxamine in thalassaemia major. Br Med J (Clin Res Ed). Apr 10 1982;284(6322):1081-4. [Medline]. [Full Text].

  81. 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. Sep 1 1994;331(9):567-73. [Medline]. [Full Text].

  82. Delea TE, Hagiwara M, Thomas SK, et al. Outcomes, utilization, and costs among thalassemia and sickle cell disease patients receiving deferoxamine therapy in the United States. Am J Hematol. Apr 2008;83(4):263-70. [Medline].

  83. Rose C. [Post transfusionnal iron overload] [French]. Rev Prat. Dec 15 2006;56(19):2141-5. [Medline].

  84. Savulescu J. Thalassaemia major: the murky story of deferiprone. BMJ. Feb 14 2004;328(7436):358-9. [Medline]. [Full Text].

  85. Olivieri NF, Brittenham GM, McLaren CE, et al. Long-term safety and effectiveness of iron-chelation therapy with deferiprone for thalassemia major. N Engl J Med. Aug 13 1998;339(7):417-23. [Medline]. [Full Text].

  86. Wanless IR, Sweeney G, Dhillon AP, et al. Lack of progressive hepatic fibrosis during long-term therapy with deferiprone in subjects with transfusion-dependent beta-thalassemia. Blood. Sep 1 2002;100(5):1566-9. [Medline]. [Full Text].

  87. Tanner MA, Galanello R, Dessi C, et al. A randomized, placebo-controlled, double-blind trial of the effect of combined therapy with deferoxamine and deferiprone on myocardial iron in thalassemia major using cardiovascular magnetic resonance. Circulation. Apr 10 2007;115(14):1876-84. [Medline]. [Full Text].

  88. Osborne RH, De Abreu Lourenço R, Dalton A, et al. Quality of life related to oral versus subcutaneous iron chelation: a time trade-off study. Value Health. Nov-Dec 2007;10(6):451-6. [Medline].

  89. Delea TE, Sofrygin O, Thomas SK, et al. Cost effectiveness of once-daily oral chelation therapy with deferasirox versus infusional deferoxamine in transfusion-dependent thalassaemia patients: US healthcare system perspective. Pharmacoeconomics. 2007;25(4):329-42. [Medline].

  90. Vichinsky E, Onyekwere O, Porter J, Swerdlow P, Eckman J, Lane P, et al. A randomised comparison of deferasirox versus deferoxamine for the treatment of transfusional iron overload in sickle cell disease. Br J Haematol. Feb 2007;136(3):501-8. [Medline]. [Full Text].

  91. 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. May 1 2006;107(9):3455-62. [Medline]. [Full Text].

  92. Piga A, Galanello R, Forni GL, et al. Randomized phase II trial of deferasirox (Exjade, ICL670), a once-daily, orally-administered iron chelator, in comparison to deferoxamine in thalassemia patients with transfusional iron overload. Haematologica. Jul 2006;91(7):873-80. [Medline]. [Full Text].

  93. Cappellini MD, Cohen A, Piga A, Bejaoui M, Perrotta S, Agaoglu L, et al. A phase 3 study of deferasirox (ICL670), a once-daily oral iron chelator, in patients with beta-thalassemia. Blood. May 1 2006;107(9):3455-62. [Medline].

  94. Meerpohl JJ, Antes G, Rücker G, Fleeman N, Motschall E, Niemeyer CM, et al. Deferasirox for managing iron overload in people with thalassaemia. Cochrane Database Syst Rev. Feb 15 2012;2:CD007476. [Medline].

  95. Detry O, Defechereux T, Honore P, et al. [Combined liver and heart transplantation in a patient with thalassemia major] [French]. Rev Med Liege. Aug 1997;52(8):532-4. [Medline].

  96. Sardi B. High-dose vitamin C and iron overload. Ann Intern Med. May 18 2004;140(10):846; author reply 846-7. [Medline].

  97. Porter JB, Davis BA. Monitoring chelation therapy to achieve optimal outcome in the treatment of thalassaemia. Best Pract Res Clin Haematol. Jun 2002;15(2):329-68. [Medline].

  98. Adams RJ, McKie VC, Hsu L, et al. Prevention of a first stroke by transfusions in children with sickle cell anemia and abnormal results on transcranial Doppler ultrasonography. N Engl J Med. Jul 2 1998;339(1):5-11. [Medline]. [Full Text].

  99. [Best Evidence] Adams RJ, Brambilla D. Discontinuing prophylactic transfusions used to prevent stroke in sickle cell disease. N Engl J Med. Dec 29 2005;353(26):2769-78. [Medline]. [Full Text].

 
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Iron status in iron deficiency and overload. NTBI = non–transferrin-bound iron; TIBC = total iron-binding capacity.
 
 
 
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