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1 Children’s Hospital Boston, Department of Laboratory Medicine, 300 Longwood Ave., Boston, MA 02115. Fax 617-713-4347; e-mail carlo.brugnara{at}tch.harvard.edu.
Abstract
Iron deficiency anemia is one of the most common diseases worldwide. In the majority of cases, the presence of hypochromic microcytic anemia and biochemical evidence for depletion of body iron stores makes the diagnosis relatively straightforward. However, in several clinical conditions, classic biochemical indices such as serum iron, transferrin saturation, and ferritin may not be informative or may not change rapidly enough to reflect transient iron-deficient states (functional iron deficiency), such as the ones that develop during recombinant human erythropoietin (r-HuEPO) therapy. The identification and treatment of iron deficiency in settings such as r-HuEPO therapy, anemia of chronic disease, and iron deficiency of early childhood may be improved by the use of red cell and reticulocyte cellular indices, which reflect in almost real time the development of iron deficiency and the response to iron therapy. In the anemia of chronic disease, measurements of plasma cytokines and iron metabolism regulators such as hepcidin (when available) may be helpful in the characterization of the pathophysiologic basis of this condition. The ratio of serum transferrin receptor (sTfR) to serum ferritin (R/F ratio) has been shown to have excellent performance in estimating body iron stores, but it cannot be used widely because of the lack of standardization for sTfR assays. The combination of hematologic markers such as reticulocyte hemoglobin content, which decreases with iron deficiency, and R/F ratio may allow for a more precise classification of anemias.
The following articles in journals at HighWire Press have cited this article:
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  J. M. Brotanek, J. Gosz, M. Weitzman, and G. Flores Secular Trends in the Prevalence of Iron Deficiency Among US Toddlers, 1976-2002 Arch Pediatr Adolesc Med, April 1, 2008; 162(4): 374 - 381. [Abstract] [Full Text] [PDF]
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 J. M. Brotanek, G. Flores, and M. Weitzman Iron-Status Indicators: In Reply Pediatrics, March 1, 2008; 121(3): 652 - 652. [Full Text] [PDF]
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 P. Barany and H.-J. Muller Maintaining control over haemoglobin levels: optimizing the management of anaemia in chronic kidney disease Nephrol. Dial. Transplant., June 1, 2007; 22(suppl_4): iv10 - iv18. [Abstract] [Full Text] [PDF]
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 W. H. Horl Clinical Aspects of Iron Use in the Anemia of Kidney Disease J. Am. Soc. Nephrol., February 1, 2007; 18(2): 382 - 393. [Full Text] [PDF]
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 D. W. Swinkels, M. C.H. Janssen, J. Bergmans, and J. J.M. Marx Hereditary Hemochromatosis: Genetic Complexity and New Diagnostic Approaches Clin. Chem., June 1, 2006; 52(6): 950 - 968. [Abstract] [Full Text] [PDF]
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 C. Cooper, W. Sears, and D. Bienzle Reticulocyte changes after experimental anemia and erythropoietin treatment of horses J Appl Physiol, September 1, 2005; 99(3): 915 - 921. [Abstract] [Full Text] [PDF]
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 C. Ullrich, A. Wu, C. Armsby, S. Rieber, S. Wingerter, C. Brugnara, D. Shapiro, and H. Bernstein Screening Healthy Infants for Iron Deficiency Using Reticulocyte Hemoglobin Content JAMA, August 24, 2005; 294(8): 924 - 930. [Abstract] [Full Text] [PDF]
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 G. Weiss and L. T. Goodnough Anemia of Chronic Disease N. Engl. J. Med., March 10, 2005; 352(10): 1011 - 1023. [Full Text] [PDF]
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S. Franck, J. Linssen, M. Messinger, and L. Thomas Potential Utility of Ret-Y in the Diagnosis of Iron-Restricted Erythropoiesis Clin. Chem., July 1, 2004; 50(7): 1240 - 1242. [Full Text] [PDF]
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