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      Biomarkers for the differentiation of anemia and their clinical usefulness

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          Abstract

          The World Health Organization defines anemia as the point at which the amount of hemoglobin in the circulation falls below World Health Organization cutoffs for specific age and sex groups. Anemia is a worldwide problem of complex etiology and is associated with many factors. The purpose of this review was to describe the biomarkers used to identify the nature of anemia in patients and in the community. The important biomarkers are the automated red cell counts, tests for nutritional deficiencies, hemoglobinopathies, and inflammation. Diseases are important potential initiators of anemia, but biomarkers of specific diseases are not included in this review, only the underlying feature common to all disease – namely, inflammation.

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          Lipocalin 2 mediates an innate immune response to bacterial infection by sequestrating iron.

          Trude Flo, Kelly D. Smith, Shintaro Sato … (2004)
          Although iron is required to sustain life, its free concentration and metabolism have to be tightly regulated. This is achieved through a variety of iron-binding proteins including transferrin and ferritin. During infection, bacteria acquire much of their iron from the host by synthesizing siderophores that scavenge iron and transport it into the pathogen. We recently demonstrated that enterochelin, a bacterial catecholate siderophore, binds to the host protein lipocalin 2 (ref. 5). Here, we show that this event is pivotal in the innate immune response to bacterial infection. Upon encountering invading bacteria the Toll-like receptors on immune cells stimulate the transcription, translation and secretion of lipocalin 2; secreted lipocalin 2 then limits bacterial growth by sequestrating the iron-laden siderophore. Our finding represents a new component of the innate immune system and the acute phase response to infection.
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            Iron biology in immune function, muscle metabolism and neuronal functioning.

            J Beard (2001)
            The estimated prevalence of iron deficiency in the world suggests that there should be widespread negative consequences of this nutrient deficiency in both developed and developing countries. In considering the reality of these estimates, the Belmont Conference seeks to reconsider the accepted relationships of iron status to physiological, biochemical and neurological outcomes. This review focuses on the biological processes that we believe are the basis for alterations in the immune system, neural systems, and energy metabolism and exercise. The strength of evidence is considered in each of the domains and the large gaps in knowledge of basic biology or iron-dependent processes are identified. Iron is both an essential nutrient and a potential toxicant to cells; it requires a highly sophisticated and complex set of regulatory approaches to meet the demands of cells as well as prevent excess accumulation. It is hoped that this review of the more basic aspects of the biology of iron will set the stage for subsequent in-depth reviews of the relationship of iron to morbidity, mortality and functioning of iron-deficient individuals and populations.
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              Adjusting plasma ferritin concentrations to remove the effects of subclinical inflammation in the assessment of iron deficiency: a meta-analysis.

              David Thurnham, Linda D McCabe, Sumanto Haldar … (2010)
              The World Health Organization recommends serum ferritin concentrations as the best indicator of iron deficiency (ID). Unfortunately, ferritin increases with infections; hence, the prevalence of ID is underestimated. The objective was to estimate the increase in ferritin in 32 studies of apparently healthy persons by using 2 acute-phase proteins (APPs), C-reactive protein (CRP) and alpha(1)-acid glycoprotein (AGP), individually and in combination, and to calculate factors to remove the influence of inflammation from ferritin concentrations. We estimated the increase in ferritin associated with inflammation (ie, CRP gt 5 mg/L and/or AGP gt 1 g/L). The 32 studies comprised infants (5 studies), children (7 studies), men (4 studies), and women (16 studies) (n = 8796 subjects). In 2-group analyses (either CRP or AGP), we compared the ratios of log ferritin with or without inflammation in 30 studies. In addition, in 22 studies, the data allowed a comparison of ratios of log ferritin between 4 subgroups: reference (no elevated APP), incubation (elevated CRP only), early convalescence (both APP and CRP elevated), and late convalescence (elevated AGP only). In the 2-group analysis, inflammation increased ferritin by 49.6% (CRP) or 38.2% (AGP; both P lt 0.001). Elevated AGP was more common than CRP in young persons than in adults. In the 4-group analysis, ferritin was 30%, 90%, and 36% (all P lt 0.001) higher in the incubation, early convalescence, and late convalescence subgroups, respectively, with corresponding correction factors of 0.77, 0.53, and 0.75. Overall, inflammation increased ferritin by ap 30% and was associated with a 14% (CI: 7%, 21%) underestimation of ID. Measures of both APP and CRP are needed to estimate the full effect of inflammation and can be used to correct ferritin concentrations. Few differences were observed between age and sex subgroups.
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                Author and article information

                Journal
                Journal ID (nlm-ta): J Blood Med
                Journal ID (iso-abbrev): J Blood Med
                Title: Journal of Blood Medicine
                Publisher: Dove Medical Press
                ISSN (Electronic): 1179-2736
                Publication date Collection: 2013
                Publication date (Electronic): 20 March 2013
                Volume: 4
                Pages: 11-22
                Affiliations
                [1 ]Nutrition Consultant, Cambridge, UK
                [2 ]Northern Ireland Centre for Food and Health, School of Biomedical Sciences, University of Ulster, Coleraine, UK
                Author notes
                Correspondence: Christine A Northrop-Clewes 46 High Street, Little Wilbraham, Cambridge CB21 5JY, UK Email christinaclewes@ 123456btinternet.com
                Article
                Publisher ID: jbm-4-011
                DOI: 10.2147/JBM.S29212
                PMC ID: 3610441
                PubMed ID: 23687454
                SO-VID: 76608782-589a-40a9-9d86-b5afe9f1127f
                Copyright © © 2013 Northrop-Clewes and Thurnham, publisher and licensee Dove Medical Press Ltd
                License:

                This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited.

                History
                Categories
                Subject: Review

                ScienceOpen disciplines: Hematology
                Keywords: iron deficiency,biological markers,blood cell count,inflammation,avitaminosis,hemoglobinopathies
                Data availability:
                ScienceOpen disciplines: Hematology
                Keywords: iron deficiency, biological markers, blood cell count, inflammation, avitaminosis, hemoglobinopathies

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