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Understanding Iron Overload

Patricia Ault
Karen Jones
CJON 2009, 13(5), 511-517 DOI: 10.1188/09.CJON.511-517

Patients receiving recurring blood transfusions as supportive therapy to treat chronic anemias, such as myelodysplastic syndromes, thalassemia, and sickle-cell disease, are at risk of iron accumulation. The clinical consequences of iron overload are progressive liver damage, cardiac disease, and endocrine disorders, which can be fatal. Nurses have a vital role in the initial assessment and monitoring of patients undergoing transfusion therapy and their ongoing care. Iron levels may be managed effectively with iron chelation therapy, and treatment guidelines recommend initiation when serum ferritin levels reach more than 1,000 mcg/L. Deferoxamine has been used effectively in clinical practice for more than 40 years. Newer agents, such as deferasirox, have introduced the option of oral therapy to manage iron overload. Those agents and practical management of patients receiving multiple blood transfusions are discussed.

References 

Abetz, L., Baladi, J.F., Jones, P., & Rofail, D. (2006). The impact of iron overload and its treatment on quality of life: Results from a literature review. <i>Health and Quality of Life Outcomes</i>, 4(1), 73.

Alessandrino, E.P., Amadori, S., Barosi, G., Cazzola, M., Grossi, A., Liberato, L.N., et al. (2002). Evidence-and consensus-based practice guidelines for the therapy of primary myelodysplastic syndromes. A statement from the Italian Society of Hematology. <i>Haematologica</i>, 87(12), 1286-1306.

Anderson, L.J., Holden, S., Davis, B., Prescott, E., Charrier, C.C., Bunce, N.H., et al. (2001). Cardiovascular T2-star (T2<sup>*</sup>) magnetic resonance for the early diagnosis of myocardial iron overload. <i>European Heart Journal</i>, 22(23), 2171-2179.

Andrews, N.C. (1999). Disorders of iron metabolism. <i>New England Journal of Medicine</i>, 341(26), 1986-1995.

Angelucci, E., Brittenham, G.M., McLaren, C.E., Ripalti, M., Baronciani, D., Giardini, C., et al. (2000). Hepatic iron concentration and total body iron stores in thalassemia major. <i>New England Journal of Medicine</i>, 343(5), 327-331.

Batra, A.S., Acherman, R.J., Wong, W.Y., Wood, J.C., Chan, L.S., Ramicone, E., et al. (2002). Cardiac abnormalities in children with sickle cell anemia. <i>American Journal of Hematology</i>, 70(4), 306-312.

Baxter, B. (2002). Management of chronic iron overload. <i>Paediatric Nursing</i>, 14(7), 14-16.

Brittenham, G.M., Griffith, P.M., Nienhuis, A.W., McLaren, C.E., Young, N.S., Tucker, E.E., et al. (1994). Efficacy of deferoxamine in preventing complications of iron overload in patients with thalassemia major. <i>New England Journal of Medicine</i>, 331(9), 567-573.

Cappellini, M.D. (2005). Overcoming the challenge of patient compliance with iron chelation therapy. <i>Seminars in Hematology</i>, 42(2, Suppl. 1), S19-S21.

Cappellini, M.D., Bejaoui, M., Agaoglu, L., Porter, J., Coates, T., Jeng, M., et al. (2007). Prospective evaluation of patient-reported outcomes during treatment with deferasirox or deferoxamine for iron overload in patients with beta-thalassemia. <i>Clinical Therapeutics</i>, 29(5), 909-917.

Cappellini, M.D., Cohen, A., Piga, A., Bejaoui, M., Perrotta, S., Agaoglu, L., et al. (2006). A phase 3 study of deferasirox (ICL670), a once-daily oral iron chelator, in patients with beta-thalassemia. <i>Blood</i>, 107(9), 3455-3462.

Cappellini, M.D., Vichinsky, E., Galanello, R., Piga, A., Williamson, P., & Porter, J.B. (2007). Long-term treatment with deferasirox (Exjade®, ICL670), a once-daily oral iron chelator, is effective in patients with transfusion-dependent anemias [Abstract]. <i>Blood</i>, 110(11), 2777.

Cohen, A.R., Galanello, R., Pennell, D.J., Cunningham, M.J., & Vichinsky, E. (2004). Thalassemia. <i>Hematology</i>, 2004, 14-34.

Cohen, A.R., & Martin, M.B. (2001). Iron chelation therapy in sickle cell disease. <i>Seminars in Hematology</i>, 38(Suppl. 1), 69-72.

Conte, D., Piperno, A., Mandelli, C., Fargion, S., Cesana, M., Brunelli, L., et al. (1986). Clinical, biochemical and histological features of primary haemochromatosis: A report of 67 cases. <i>Liver</i>, 6(5), 310-315.

Cunningham, M.J., Macklin, E.A., Neufeld, E.J., & Cohen, A.R. (2004). Complications of beta-thalassemia major in North America. <i>Blood</i>, 104(1), 34-39.

Ehlers, K.H., Giardina, P.J., Lesser, M.L., Engle, M.A., & Hilgartner, M.W. (1991). Prolonged survival in patients with beta-thalassemia major treated with deferoxamine. <i>Journal of Pediatrics</i>, 118(4, Pt. 1), 540-545.

el-Hazmi, M.A., Bahakim, H.M., & al-Fawaz, I. (1991). Endocrine functions in sickle cell anaemia patients. <i>Journal of Tropical Pediatrics</i>, 38(6), 307-313.

Erba, H.P. (2003). Recent progress in the treatment of myelodysplastic syndrome in adult patients. <i>Current Opinion in Oncology</i>, 15(1), 1-9.

Fung, E.B., Harmatz, P.R., Lee, P.D., Milet, M., Bellevue, R., Jeng, M.R., et al. (2006). Increased prevalence of iron-overload associated endocrinopathy in thalassaemia versus sickle-cell disease. <i>British Journal of Haematology</i>, 135(4), 574-582.

Gabutti, V., & Piga, A. (1996). Results of long-term iron-chelating therapy. <i>Acta Haematology</i>, 95(1), 26-36.

Galanello, R., Piga, A., Forni, GL., Bertrand, Y., Foschini, M.L., Bordone, E., et al. (2006). Phase II clinical evaluation of deferasirox, a once-daily oral chelating agent, in pediatric patients with betathalassemia major. <i>Haematologica</i>, 91(10), 1343-1351.

Hellstrom-Lindberg, E., Gulbrandsen, N., Lindberg, G., Ahlgren, T., Dahl, I.M., Dybedal, I., et al. (2003). A validated decision model for treating the anaemia of myelodysplastic syndromes with erythropoietin + granulocyte colony-stimulating factor: Significant effects on quality of life. <i>British Journal of Haematology</i>, 120(6), 1037-1046.

Jaeger, M., Aul, C., Sohngen, D., Germing, U., & Schneider, W. (1992). [Secondary hemochromatosis in polytransfused patients with myelodysplastic syndromes]. <i>Beitrage zur Infusionstherapie</i>, 30, 464-468.

Jansen, A.J., Essink-Bot, M.L., Beckers, E.A., Hop, W.C., Schipperus, M.R., & Van Rhenen, D.J. (2003). Quality of life measurement in patients with transfusion-dependent myelodysplastic syndromes. <i>British Journal of Haematology</i>, 121(2), 270-274.

Jensen, P.D. (2004). Evaluation of iron overload. <i>British Journal of Haematology</i>, 124(6), 697-711.

Kushner, J.P., Porter, J.P., & Olivieri, N.F. (2001). Secondary iron overload. <i>Hematology</i>, 2001, 47-61.

List, A.F., Esposito, J., Decker, J., Baer, M.R., Powell, B., Steensma, D., et al. (2006). Iron parameters in 84 MDS patients enrolled in a deferasirox (Exjade®, ICL670) multicenter trial [Abstract]. <i>Blood</i>, 108(11), 4847.

Liu, P., & Olivieri, N. (1994). Iron overload cardiomyopathies: New insights into an old disease. <i>Cardiovascular Drugs and Therapy</i>, 8(1), 101-110.

National Comprehensive Cancer Network. (2009). <i>NCCN Clinical Practice Guidelines in Oncology™: Myelodysplastic syndromes</i> [v.1.2010]. Retrieved August 27, 2009, from <a target="_blank" href='http://www.nccn.org/professionals/physician_gls/pdf/mds.pdf'>http://www....

National Institutes of Health. (2002). The management of sickle cell disease (4th ed., NIH Publication No 02-2117). Retrieved August 26, 2009, from <a target="_blank" href='http://www.nhlbi.nih.gov/health/prof/blood/sickle/sc_mngt.pdf'>http://ww...

Novartis Pharmaceuticals. (1998). <i>Desferal patient leaflet.</i> Basel, Switzerland: Author.

Novartis Pharmaceuticals. (2005). <i>Desferal®</i> (deferoxamine) [Package insert]. East Hanover, NJ: Author.

Olivieri, N.F., & Brittenham, G.M. (1997). Iron-chelating therapy and the treatment of thalassemia. <i>Blood</i>, 89(3), 739-761.

Olivieri, N.F., Nathan D.G., MacMillan J.H., Wayne A.S., Liu P.P., Mc-Gee A., et al. (1994). Survival in medically treated patients with homozygous beta-thalassemia. <i>New England Journal of Medicine</i>, 331(9), 574-578

Payne, K., Desrosiers, M.P., Proskorovsky, I., Ishak, K., & Baladi, J.F. (2006). Ferritin levels, non-compliance and adverse events in relation to infused iron chelation therapy in an international cohort of patients from actual practice. <i>Haematologica</i>, 91(Suppl. 1), 1059.

Porter, J., Galanello, R., Saglio, G., Neufeld, E.J., Vichinsky, E., Cappellini, M.D., et al. (2008). Relative response of patients with myelodysplastic syndromes and other transfusion-dependent anaemias to deferasirox (ICL670): A 1-yr prospective study. <i>European Journal of Haematology</i>, 80(2), 168-176.

Porter, J.B. (2001). Practical management of iron overload. <i>British Journal of Haematology</i>, 115(2), 239-252.

Porter, J.B., Abeysinghe, R.D., Marshall, L., Hider, R.C., & Singh, S. (1996). Kinetics of removal and reappearance of non-transferrin-bound plasma iron with deferoxamine therapy. <i>Blood</i>, 88(2), 705-713.

Porter, J.B., & Davis, B.A. (2002). Monitoring chelation therapy to achieve optimal outcome in the treatment of thalassaemia. <i>Best Practices and Research. Clinical Haematology</i>, 15(2), 329-368.

Roth, C., Pekrun, A., Bartz, M., Jarry, H., Eber, S., Lakomek, M., et al. (1997). Short stature and failure of pubertal development in thalassaemia major: Evidence for hypothalamic neurosecretory dysfunction of growth hormone secretion and defective pituitary gonadotropin secretion. <i>European Journal of Pediatrics</i>, 156(10), 777-783.

Samaras, A.T., Bennett, C.L., & Lai, S.Y. (2008). Transfusion in patients with chemotherapy-induced anemia. <i>Advanced Studies in Medicine</i>, 8(10), 352-356.

Schafer, A.I., Cheron, R.G., Dluhy, R., Cooper, B., Gleason, R.E., Soeldner, J.S., et al. (1981). Clinical consequences of acquired transfusional iron overload in adults. <i>New England Journal of Medicine</i>, 304(6), 319-324.

Shalitin, S., Carmi, D., Weintrob, N., Phillip, M., Miskin, H., Kornreich, L., et al. (2005). Serum ferritin level as a predictor of impaired growth and puberty in thalassemia major patients. <i>European Journal of Haematology</i>, 74(2), 93-100.

Silliman, C.C., Peterson, V.M., Mellman, D.L., Dixon, D.J., Hambidge, K.M., & Lane, P.A. (1993). Iron chelation by deferoxamine in sickle cell patients with severe transfusion-induced hemosiderosis: A randomized, double-blind study of the dose-response relationship. <i>Journal of Laboratory and Clinical Medicine</i>, 122(1), 48-54.

St. Pierre, T.G., Clark, P.R., & Chua-Anusorn, W. (2005). Measurement and mapping of liver iron concentrations using magnetic resonance imaging. <i>Annals of New York Academies of Science</i>, 1054, 379-385.

Telfer, P.T., Prestcott, E., Holden, S., Walker, M., Hoffbrand, A.V., & Wonke, B. (2000). Hepatic iron concentration combined with longterm monitoring of serum ferritin to predict complications of iron overload in thalassaemia major. <i>British Journal of Haematology</i>, 110(4), 971-977.

Thalassaemia International Federation. (2008). <i>Guidelines for the clinical management of thalassaemia</i> (2nd ed.). Retrieved September 9, 2009, from <a target="_blank" href='http://www.thalassaemia.org.cy/pdf/Guidelines_2nd_revised_edition_EN.pdf...

Treadwell, M.J., Law, A.W., Sung, J., Hackney-Stephens, E., Quirolo, K., Murray, E., et al. (2005). Barriers to adherence of deferoxamine usage in sickle cell disease. <i>Pediatric Blood Cancer</i>, 44(5), 500-507.

Vichinsky, E. (2008). Clinical application of deferasirox: Practical patient management. <i>American Journal of Hematology</i>, 83(5), 398-402.

Vichinsky, E., Coates, T.D., Thompson, A.A., Mueller, B.U., Lagrone, D., & Heeney, M.M. (2007). Long-term efficacy and safety of deferasirox (Exjade®, ICL670), a once-daily oral iron chelator, in patients with sickle cell disease (SCD) [Abstract]. <i>Blood</i>, 110(11), 3395.

Vichinsky, E., Fischer, R., Pakbaz, Z., Onyekwere, O., Porter, J., Swerdlow, P., et al. (2005). Satisfaction and convenience of chelation therapy in patients with sickle cell disease (SCD): Comparison between deferasirox (Exjade®, ICL670) and deferoxamine (DFO) [Abstract]. <i>Blood</i>, 106(11), 2334.

Vichinsky, E., Onyekwere, O., Porter, J., Swerdlow, P., Eckman, J., Lane, P., et al. (2007). A randomized comparison of deferasirox versus deferoxamine for the treatment of transfusional iron overload in sickle cell disease. <i>British Journal of Haematology</i>, 136(3), 501-508.

Weintraub, L.R., Conrad, M.E., & Crosby, W.H. (1965). Regulation of the intestinal absorption of iron by the rate of erythropoiesis. <i>British Journal of Haematology</i>, 11(4), 432-438.

Weiss, G., & Goodnough, L.T. (2005). Anemia of chronic disease. <i>New England Journal of Medicine</i>, 352(10), 1011-1023.

Wolfe, L., Olivieri, N., Sallan, D., Colan, S., Rose, V., Propper, R., et al. (1985). Prevention of cardiac disease by subcutaneous deferoxamine in patients with thalassemia major. <i>New England Journal of Medicine</i>, 312(25), 1600-1603.

Wood, J.C., Enriquez, C., Ghugre, N., Otto-Duessel, M., Aguilar, M., Nelson, M.D., et al. (2005). Physiology and pathophysiology of iron cardiomyopathy in thalassemia. <i>Annals of the New York Academies of Science</i>, 1054, 386-395.

World Health Organization. (2003). <i>Adherence to long-term therapies: Evidence for action.</i> Retrieved September 10, 2009, from <a target="_blank" href='http://www.who.int/chp/knowledge/publications/adherence_full_report.pdf'...