Indicators of Iron Deficiency

Reference from the joint report of FAO/WHO expert consultation on Human Vitamin and Minerals verbatim.

70. Hallberg, L. 1993. Screening for iron deficiency: an analysis based on bone-marrowexaminations and serum ferritin determinations in a population sample of women. Br. J. Haematol., 85: 787-798.

The absence of iron stores (iron deficiency) can be diagnosed by showing that there is no stainable iron in the reticuloendothelial cells in bone marrow smears or more easily by a low concentration of ferritin in serum (≤15 μg/l). Even if an absence of iron stores per se may not necessarily be associated with any immediate adverse effects, it is a reliable and good indirect indicator of iron-deficient erythropoiesis and of an increased risk of a compromised supply of iron to different tissues. Even before iron stores are completely exhausted, the supply of iron to the erythrocyte precursors in the bone marrow is compromised, leading to iron-deficient erythropoiesis (70).

75. Pilch, S.M. & Senti, F.R.E. 1984. Assessment of the iron nutritional status of the US population based on data collected in the second National Health and Nutrition Examination Survey, 1976-1980. Prepared for the Food and Drug Administration under Contract no FDA 223-83-2384. Bethesda, MD, Life Sciences Research Office, Federation of American Societies for Experimental Biology.

76. Group ESW. 1985. Summary of a report on assessment of the iron nutritional status of the United States population. Am. J. Clin. Nutr., 2: 1318-1330.

A possible explanation is that the rate of release of iron from stores is influenced by the amount of iron remaining. As mentioned above it can then be assumed that the supply of iron to other tissues needing iron is also insufficient because the identical transport system is used. During the development of iron deficiency haemoglobin concentration, transferrin concentration, transferrin saturation, transferrin receptors in plasma, erythrocyte protoporphyrin, and erythrocyte indexes are changed. All these methods, however, show a marked overlap between normal and iron-deficient subjects, that makes it impossible to identify the single subject with mild iron deficiency by using any of these methods. Therefore, these tests have been used in combination (e.g., for interpreting results from the second National Health and Nutrition Examination Survey in the United States of America [75, 76]). 

The diagnostic specificity then increases but the sensitivity decreases, and thus the true prevalence of iron deficiency is markedly underestimated if multiple diagnostic criteria are used. By definition in screening for iron deficiency, the more tests that are used the higher is the diagnostic specificity but the lower is the sensitivity of the procedure. Fortunately, a low serum ferritin, ≤15μg/l is always associated with an iron-deficient erythropoiesis. 

The use of serum ferritin alone as a measure will also underestimate the true prevalence of iron deficiency but to a lesser degree than when the combined criteria are used. A diagnosis of iron deficiency anaemia can be suspected if anaemia is present in subjects who are iron-deficient as described above. Preferably, to fully establish the diagnosis, the subjects should respond adequately to iron treatment. The pitfalls with this method are the random variation in haemoglobin concentrations over time and the effect of the regression towards the mean when a new measurement is made.

77. Hulthén, L. 1998. Effect of a mild infection on serum ferritin concentration -clinical and epidemiological implications. Eur. J. Clin. Nutr., 52: 1-4.

78. Osler, M., Minman, N. & Heitman, B.L. 1998. Dietary and non-dietary factors associated with iron status in a cohort of Danish adults followed for six years. Eur. J. Clin. Nutr., 52: 459-63.

79. Leggett, B.A. 1990. Factors affecting the concentrations of ferritin in serum in a healthy Australian population. Clin. Chem., 36: 1350 1555.

The use of serum ferritin has improved the diagnostic accuracy of iron deficiency. It is the only simple method available to detect early iron deficiency. Its practical value is somewhat reduced, however, by the fact that serum ferritin is a very sensitive acute-phase reactant and may be increased for weeks after a simple infection with fever for a day or two (77). Several other conditions, such as use of alcohol (78, 79), liver disease, and collagen diseases, may also increase serum ferritin concentrations. Determination of transferrin receptors in plasma has also been recommended in the diagnosis of iron deficiency.

80. Cook, J.D., Skikne, B. & Baynes, R. 1996. The use of transferrin receptor for the assessment of iron status. In: Hallberg LA, Asp N-G, eds. Iron nutrition in health an disease, London: John Libbey & Co. 

Its advantage is that it is not influenced by infections. Its main use is in subjects who are already anaemic and it is not sensitive for the early diagnosis of iron deficiency. The use of a combination of determinations of serum ferritin and serum transferrin receptors has also been suggested (80).