Transfusion-Induced Iron Overload Workup

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

Laboratory Studies

To date, no perfect laboratory marker for iron overload exists.

Serum iron studies

Iron indices behave in a predictable fashion in states of low and high iron (see the image below).

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

Serum ferritin has been extensively used as an easily accessible serum marker for transfusion-induced iron overload. The ferritin level that has been used as a cutoff point for iron toxicity has varied in studies from 1000 ng/mL to 3000 ng/mL.[41, 42] The major drawbacks of ferritin are a lack of specificity and interpatient variability.[42] Inflammation, disseminated malignancy, and chronic diseases can also cause large amounts of ferritin to be released in the circulation, making a single elevated reading unreliable.[43]

Low serum ferritin levels may be misleading by providing a false sense of security when patients are at risk of end-organ damage such as cardiomyopathy.[44] Ferritin has also been shown to have a prognostic value. In one study of β-thalassemia major, for patients in whom more than 67% of ferritin measurements exceeded 2500 ng/nL, the estimated disease-free survival was 38% after 10 years of therapy and 18% after 15 years.[14]

Serum iron is increased in cases of iron overload and the total iron-binding capacity (TIBC) is decreased. The relationship between serum iron and total body iron is nonlinear, and the results are dependent on the method used.[45]

Transferrin saturation can be easily measured and is a surrogate marker for NTBI, although this is far from perfect.[46] A transferrin saturation above 50% is suggestive of a high iron load, but this is a dynamic number and may vary with inflammation.

NTBI and LPI are very specific for iron overload and have promising value as monitoring parameters for clinical response to chelation therapy.[47] However, the lack of a standardized assay and limited data for general use for transfusion-induced iron overload makes it necessary to further investigate the use of NTBI and LPI.

Hepcidin measurement in serum and urine have been performed using mass spectrometry, and this may be a feasible marker in the future.[48]

The patient's complete blood cell (CBC) count should be monitored for the hemoglobin/hematocrit to maintain a high threshold for transfusion. Liver function tests, especially alanine aminotransferase (ALT) and aspartate aminotransferase (AST), should be monitored. In patients who develop diabetes mellitus, the usual parameters, such as hemoglobin A1C (HbA1C) and glucose, should be monitored.

Next

Imaging Studies

Computed tomography (CT) scanning has a limited sensitivity (63%) for the assessment of hepatic iron overload.[49] An elevated hepatic CT density associated with an elevated serum ferritin indicates iron overload; however, a normal hepatic CT density does not exclude iron overload.[50] CT scanning is not sensitive when serum ferritin is less than 1000 mcg/L.[51]

Superconducting quantum interference device (SQUID) magnetic measurements of liver iron in patients with iron overload are quantitatively equivalent to biochemical determinations on tissue obtained by biopsy.[52] SQUID can also measure spleen iron content and can be used for monitoring the clinical response to chelation therapy.[53] However, the complexity, cost, and technical demands of the liquid helium–cooled superconducting instruments required at present necessitate restricted clinical access to this method.[54] The latest generation SQUID can be used at room temperature.[55]

Magnetic resonance imaging (MRI) is the noninvasive means of imaging choice and can detect iron deposition in the liver, heart,[56] joints, and pituitary. MRI assessment of myocardial iron loading with the use of gradient echo T2* measurements has reliable reproducibility and has been validated in multiple centers.[57] Quantitative R2* MRI using the transverse magnetic relaxation rate is useful for the measurement of hepatic iron content at facilities with experienced personnel and the proper equipment[58]

MRI is useful to assess pituitary iron overload in patients with transfusional hemochromatosis and secondary hypogonadism by detection of a significant decreased signal intensity of the anterior lobe of the pituitary gland on T2-weighted images.[59] The degree of reduction of the pituitary-to-fat signal intensity ratio correlates with the presence of hypogonadotropic hypogonadism, with a sensitivity of 90%, a specificity of 89%, and an overall accuracy of 89%.[60]

In addition, MRI can be used for the accurate detection of hemochromatosis in the joints of thalassemia patients receiving multiple transfusions.[61] However, iron deposition in the pancreas cannot be reliably predicted by MRI.[62] MRI mapping accurately estimates hepatic iron concentration in patients with transfusion-dependent thalassemia and sickle cell disease.[63] MRI is rapid, noninvasive, and cost effective, and could limit the use of liver biopsy to assess liver iron content.[64]

Previous
Next

Other Tests

When peripheral flow cytometry is performed, patients with transfusion-induced iron overload seem to exhibit a high expression of CD2 and a low expression of CD38 surface markers on the helper T (Th)-cell subset.[65]

Previous
Next

Procedures

Liver biopsy is the criterion standard for measuring iron deposition in the liver and a surrogate for other organs. The hepatic iron concentration is a reliable indicator of total body iron stores.[66] Liver iron concentration (LIC) is measured in mg/g of dry weight of liver and may vary up to 23% between fresh and paraffin-embedded samples.[67] A poor correlation is observed between serum ferritin and the quantitative iron on liver biopsy.[68] CT-guided and transjugular liver biopsies appear less risky. Complications of liver biopsies are reported in 0.06-0.32% of the patients. Death as a direct result of liver biopsy is extremely rare (0.009-0.12%).[69]

Endomyocardial biopsy is an insensitive method of determining early myocardial iron deposition because of the location of the iron and the variability of the sampling.[70]

Previous
Next

Histologic Findings

Iron accumulation and fibrosis are the common features found in patients with thalassemia and liver damage, except that thalassemia/hemoglobin H disease exhibit lesser hepatic damage. The degrees of iron deposition and fibrosis are higher in splenectomized and cirrhotic individuals than in nonsplenectomized and noncirrhotic patients.[71]

The subcellular changes on electron microscopy are swollen mitochondria, with the presence of an electron-dense matrix and ruptured mitochondrial membrane. Proliferation of smooth endoplasmic reticulum (ER), and dilatated rough ER are observed. Increases in lysosomal hemosiderin in hepatocytes and in Kupffer cells are demonstrated. The pattern of liver cell damage is similar to that of viral hepatitis.[71]

Previous
Next

Staging

Hepatic iron overload is classified as mild (< 7 mg/g dry weight), moderate (7-15 mg/g dry weight), or severe (>15 mg/g dry weight).[72]

Previous
Proceed to Treatment & Management
 
 
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].

 
Previous
Next
 
Iron status in iron deficiency and overload. NTBI = non–transferrin-bound iron; TIBC = total iron-binding capacity.
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2012 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.