Abstract
Background and methods:To determine the diagnostic values of laboratory tests used in the diagnosis of iron-deficiency anemia, the authors conducted a systematic over-view of the relevant literature. Computerized searches of the MEDLINE database yielded 1,179 potentially relevant citations. Fifty-five studies included the results of laboratory tests and histologic examination of the bone marrow for at least 50% of an identifiable patient group. In these 55 studies, quality was assessed and descriptive information concerning the study populations, the tests conducted, and the results was extracted, all in duplicate.
Results:Serum ferritin radioimmunoassay was by far the most powerful test, with an area under the receiver operating characteristic curve of 0.95. Test properties differed for populations of patients with inflammatory, liver, or neoplastic disease and patients without these conditions. Likelihood ratio lines, which allow precise interpretation of results across the entire range of ferritin concentration values, were constructed for the individual populations.
Conclusion:Serum ferritin radioimmunoassay is an extremely powerful test for the diagnosis of iron-deficiency anemia and, appropriately interpreted, can be applied to the complete range of patients.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Sackett DL, Haynes RB, Tugwell P. Clinical epidemiology, a basic science for clinicians. Boston/Toronto: Little, Brown, 1985.
Arkin CF, Wachtel MS. How many patients are necessary to assess test performance? JAMA. 1990;263:275–8.
Heckerling PS. Confidence in diagnostic testing (editorial). J Gen Intern Med. 1988;3:604–6.
Stuckey WJ. Common anemias: a practical guide to diagnosis and management. Geriatrics. 1983;38:42–8.
Fischer SL, Fischer SP. Mean corpuscular volume. Arch Intern Med. 1983;143:282–3.
Witte DA. Laboratory tests to confirm or exclude iron deficiency. Lab Med. 1985;16:671–5.
Worwood M. Serum ferritin. Clin Sci. 1986;70:215–20.
Besa EC. Approach to mild anemia in the elderly. Clin Geriatr Med. 1988;4:43–55.
Oxman AD, Guyatt GH. Guidelines for reading literature reviews. Can Med Assoc J. 1988;138:697–703.
Chung-hua I, Hseuh T. Iron deficiency in late pregnancy: observation on free erythrocyte protoporphyrin, transferrin saturation, and marrow iron in 16 cases. Chin Med J. 1984;64:108–11.
Milman N. Plasma transferrin and the relation to iron status in patients with chronic uraemia. Clin Nephrol. 1981;16:314–20.
Milman N, Christensen TE, Pedersen NS, Visfeldgt J. Serum ferritin and bone marrow iron in non-dialysis, peritoneal dialysis and haemodialysis patients with chronic renal failure. Acta Med Scand. 1980;207:201–5.
Milman N, Christensen TE, Visfeldgt J. Diagnostic efficiency of various laboratory tests in the assessment of bone marrow iron stores in patients with chronic uraemia. Scand J Haematol. 1981;26:257–64.
Cohen J. Weighted kappa: nominal scale agreement with provision for scaled disagreement or partial credit. Psychol Bull. 1968;70:213–20.
Cicchetti DV, Fleiss JL. A comparison of the null distributions of weighted kappa and the c ordinal statistic. Appl Psychol Measurement. 1977;1:195–201.
Delong FR, Delong DM, Clarke-Pearson DL. Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics. 1988;44:837–45.
Department of Clinical Epidemiology and Biostatistics. Interpretation of diagnostic data: 5. How to do it with simple maths. Can Med Assoc J. 1983;129:22–9.
Breslow NE, Day NE. Statistical methods in cancer research. Volume 1 — the analysis of case—control studies. Lyon, France: IARC Scientific Publications, 1980.
Albert A. On the use and computation of likelihood ratios in clinical chemistry. Clin Chem. 1982;28:1113–9.
Jakobsen E, Engeset A, Sandstad B, Aas M. Serum ferritin and bone marrow haemosiderin in patients with malignancies and in health controls. Scand J Haematol. 1982;28:264–71.
Raper CGL, Rosen C, Choudhury M. Automated red cell indices and marrow iron reserves in geriatric patients. J Clin Pathol. 1977;30:353–5.
Blend MJ, Tischler IW, Chernicoff DP, Caleel GT. Correlation of serum ferritin concentration with bone marrow iron stores. J Am Osteopath Assoc. 1981;80:805–9.
Barnett MD, Gordon YB, Amess JAL, Mollin DL. Measurement of ferritin in serum by radioimmunoassay. J Clin Pathol. 1978;31:742–8.
Brink S, Van Schalkwyk DJ. Serum ferritin and mean corpuscular volume as predictors of bone marrow iron stores. S Afr Med J. 1982;61(12):432–4.
Forman DT, Vye MV. Immunoradiometric serum ferritin concentration compared with stainable bone-marrow iron as indices to iron stores. Clin Chem. 1980;26:145–7.
Oertel BM, Bombik BM, Stephan M, Gerhartz H. Ferritin in bone marrow and serum in iron deficiency and iron overload. Blut. 1978;37:113–7.
Walsh JR, Fredrickson M. Serum ferritin, free erythrocyte protoporphyrin, and urinary iron excretion in patients with iron disorders. Am J Med Sci. 1977;273:293–300.
Baynes RD, Bothwell TH, Bezwoda WR, et al. Hematologic and iron-related measurements in rheumatoid arthritis. Am J Clin Pathol. 1987;87:196–200.
Witte DL, Angstadt DS, Davis SH, Schrantz RD. Predicting bone marrow iron stores in anemic patients in a community hospital using ferritin and erythrocyte sedimentation rate. Am J Clin Pathol. 1988;90:85–7.
Isa L, Jean G, Silvani A, et al. Evaluation of iron stores in patients with alcoholic liver disease: role of red cell ferritin. Acta Haematol. 1988;80:85–8.
Brown RD, Benfatto J, Gibson J, Kronenberg H. Red cell ferritin and iron stores in patients with chronic disease. Eur J Haematol. 1988;40:136–41.
Lindstedt G, Lundberg P, Bjorn-Rasmussen E, Magnussen B. Serum-ferritin and iron-deficiency anaemia in hospital patients. Lancet. 1980;1:205–6.
Ballas SK. Normal serum iron and elevated total iron-binding capacity in iron-deficiency states. Am J Clin Pathol. 1979;71:401–3.
Beck JR, Gibbons AB, Cornwell GG, Rawnsley HM. Multivariate approach to predictive diagnosis of bone-marrow iron stores. Am J Clin Pathol. 1979;70(suppl):S665-S670.
Krause JR, Stolc V. Serum ferritin and bone marrow biopsy iron stores. II: Correlation with low serum iron and Fe/TIBC ratio less than 15%. Am J Clin Pathol. 1980;74(suppl):S461-S464.
Krause JR, Stolc V. Serum ferritin and bone marrow biopsy iron stores. I: Correlation with absence of iron in biopsy specimens. Am J Clin Pathol. 1979;72(suppl):S817-S820.
Sheehan RG, Newton MJ, Frenkel EP. Evaluation of a packaged kit assay of serum ferritin and application to clinical diagnosis of selected anemias. Am J Clin Pathol. 1978;70:79–84.
Puolakka J. Serum ferritin in the evaluation of iron status in young healthy women. Acta Obstet Gynecol Scand. 1980;95(suppl):S35-S41.
Witte DL, Kraemer DF, Johnson GF, et al. Prediction of bone marrow iron findings from tests performed on peripheral blood. Am J Clin Pathol. 1986;85:202–6.
Patterson C, Turpie ID, Benger AM. Assessment of iron stores in anemic geriatric patients. J Am Geriatr Soc. 1985;33:764–7.
Blumberg AB, Marti HRM, Graber CG. Serum ferritin and bone marrow iron in patients undergoing continuous ambulatory peritoneal dialysis. JAMA. 1983;250:3317–9.
Sharma JC, Roy SN. Value of serum ferritin as an index of iron deficiency in elderly anaemic patients. Age Ageing. 1984;13:248–50.
Harju E, Pakarinenen A, Larmi T. A comparison between serum ferritin concentration and the amount of bone marrow stainable iron. Scand J Clin Lab Invest. 1984;44:555–6.
Ali MAM, Luxton AW, Walker WHC. Serum ferritin concentration and bone marrow iron stores: a prospective study. Can Med Assoc J. 1978;118:945–6.
Mazza J, Barr RM, McDonald JWD, Valberg LS. Usefulness of the serum ferritin concentration in the detection of iron deficiency in a general hospital. Can Med Assoc J. 1978;119:884–6.
Kalmin ND, Bobson EB, Bettigole RE. Serum ferritin and marrow iron stores. N Y State J Med. 1978;78:1052–5.
Smith RJ, Davis P, Thomson BR, et al. Serum ferritin levels in the anemia of rheumatoid arthritis. J Rheumatol. 1977;4(suppl):S389-S392.
Ali M, Rigolosi R, Fayemi AO, et al. Failure of serum ferritin levels to predict bone-marrow iron content after intravenous iron-dextran therapy. Lancet. 1982;1:652–5.
McLaren GD, Carpenter JT, Nino HV. Erythrocyte protoporphyrin in the detection of iron deficiency. Clin Chem. 1975;21:1121–7.
Sorbie J, Valberg LS, Corbett WEN, Ludwig J. Serum ferritin, cobalt excretion and body iron status. Can Med Assoc J. 1975;112:1173–8.
Hussein S, Prieto J, O’Shea M, et al. Serum ferritin assay and iron status in chronic renal failure and haemodialysis. Br Med J. 1975;1:546–8.
Wachtel TJ, Reuben DB, Fulton JP, Wartman SA. The use of “range of uncertainty.” Med Decis Making. 1985;5:325–34.
Charache S, Gittelsohn AM, Allen H, et al. Noninvasive assessment of tissue iron stores. Am J Clin Pathol. 1987;88:333–7.
Paine CJ, Polk A, Eichner ER. Analysis of anemia in medical inpatients. Am J Med Sci. 1974;268:37–44.
Bentley DP, Williams P. Serum ferritin concentration as an index of storage iron in rheumatoid arthritis. J Clin Pathol. 1974;27:786–8.
Child Ja, Brozovic B, Dyer NH, et al. The diagnosis of iron deficiency in patients with Crohn’s disease. Gut. 1973;14:642–8.
Beallo R, Dallman PR, Schoenfeld PY, Humphreys MH. Serum ferritin and iron deficiency in patients on chronic haemodialysis. Trans Am Soc Artif Intern Organs. 1976;22:73–9.
Beutler E, Robson MJ, Buttenwieser E. A comparison of the plasma iron, iron-binding capacity, sternal marrow iron and other methods in the clinical evaluation of iron stores. Ann Intern Med. 1958;48:60–80.
Oluboyede OA. Iron studies in pregnant and non-pregnant women with haemoglobin SS or SC disease. Br J Obstet Gynaecol. 1980;87:989–95.
Lipshchitz DA, Cook JD, Finch CA. A clinical evaluation of serum ferritin as an index of iron stores. N Engl J Med. 1974;290:1213–6.
Gokal R, Millard PR, Weatherall DJ, et al. Iron metabolism in haemodialysis patients. Q J Med. 1979;48:369–91.
Addison GM, Beamish MR, Hales CN, et al. An immunoradiometric assay for ferritin in the serum of normal subjects and patients with iron deficiency and iron overload. J Clin Pathol. 1972;25:326–9.
England JM, Ward SM, Down MC. Microcytosis, anisocytosis and the red cell indices in iron deficiency. Br J Haematol. 1976;34:589–97.
Bartels U, Pederson NS, Jarnum S. Iron absorption and serum ferritin in chronic inflammatory bowel disease. Scand J Gastorenterol. 1978;13:649–56.
Thompson WG, Meola T, Lipkin M, Freedman ML. Red cell distribution width, mean corpuscular volume, and transferrin saturation in the diagnosis of iron deficiency. Arch Intern Med. 1988;148:2128–30.
Witte DL, Dick F, Goeken J, et al. C-reactive protein aids interpretation of serum ferritin. Clin Chem. 1985;31:1011.
Nelson R, Chawla M, Connolly P, LaPorte J. Ferritin as an index of bone marrow iron stores. South Med J. 1978;71:1482–4.
Puolakka J, Janne O, Pakarinen A, Bihko R. Serum ferritin in the diagnosis of anemia during pregnancy. Acta Obstet Gynecol Scand. 1980;95:57–63.
Wohlenberg H, Panitz N, Wacheck W. Hypoferramie und serumferritin. Dtsch Med Wochenschr. 1980;105:1527–30.
Leyland MJ, Ganguli PC, Blower D, Delamore IW. Immunoradiometric assay for ferritin in human serum. Scand J Haematol. 1975;14:385–92.
Guyatt GH, Patterson C, Ali M, et al. Diagnosis of iron deficiency anemia in the elderly. Am J Med. 1990;88:205–9.
Mulrow CD. The medical review article: state of the science. Ann Intern Med. 1987;106:485–8.
Patterson C, Guyatt GH, Singer J, et al. Iron deficiency anemia in the elderly: the diagnostic process. Can Med Assoc J. 1991;144:435–40.
Author information
Authors and Affiliations
Additional information
Supported in part by the Ontario Ministry of Health. Drs. Guyatt and Oxman are Career Scientists of the Ontario Ministry of Health.
An erratum to this article is available at http://dx.doi.org/10.1007/BF02599160.
Rights and permissions
About this article
Cite this article
Guyatt, G.H., Oxman, A.D., Ali, M. et al. Laboratory diagnosis of iron-deficiency anemia. J Gen Intern Med 7, 145–153 (1992). https://doi.org/10.1007/BF02598003
Issue Date:
DOI: https://doi.org/10.1007/BF02598003