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Laboratory diagnosis of iron-deficiency anemia

An overview

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An Erratum to this article was published on 01 July 1992

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.

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References

  1. Sackett DL, Haynes RB, Tugwell P. Clinical epidemiology, a basic science for clinicians. Boston/Toronto: Little, Brown, 1985.

    Google Scholar 

  2. Arkin CF, Wachtel MS. How many patients are necessary to assess test performance? JAMA. 1990;263:275–8.

    Article  PubMed  CAS  Google Scholar 

  3. Heckerling PS. Confidence in diagnostic testing (editorial). J Gen Intern Med. 1988;3:604–6.

    Article  PubMed  CAS  Google Scholar 

  4. Stuckey WJ. Common anemias: a practical guide to diagnosis and management. Geriatrics. 1983;38:42–8.

    PubMed  CAS  Google Scholar 

  5. Fischer SL, Fischer SP. Mean corpuscular volume. Arch Intern Med. 1983;143:282–3.

    Google Scholar 

  6. Witte DA. Laboratory tests to confirm or exclude iron deficiency. Lab Med. 1985;16:671–5.

    Google Scholar 

  7. Worwood M. Serum ferritin. Clin Sci. 1986;70:215–20.

    PubMed  CAS  Google Scholar 

  8. Besa EC. Approach to mild anemia in the elderly. Clin Geriatr Med. 1988;4:43–55.

    PubMed  CAS  Google Scholar 

  9. Oxman AD, Guyatt GH. Guidelines for reading literature reviews. Can Med Assoc J. 1988;138:697–703.

    CAS  Google Scholar 

  10. 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.

    Google Scholar 

  11. Milman N. Plasma transferrin and the relation to iron status in patients with chronic uraemia. Clin Nephrol. 1981;16:314–20.

    PubMed  CAS  Google Scholar 

  12. 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.

    Article  PubMed  CAS  Google Scholar 

  13. 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.

    Article  PubMed  CAS  Google Scholar 

  14. Cohen J. Weighted kappa: nominal scale agreement with provision for scaled disagreement or partial credit. Psychol Bull. 1968;70:213–20.

    Article  CAS  PubMed  Google Scholar 

  15. 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.

    Article  Google Scholar 

  16. 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.

    Article  PubMed  CAS  Google Scholar 

  17. 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.

    Google Scholar 

  18. Breslow NE, Day NE. Statistical methods in cancer research. Volume 1 — the analysis of case—control studies. Lyon, France: IARC Scientific Publications, 1980.

    Google Scholar 

  19. Albert A. On the use and computation of likelihood ratios in clinical chemistry. Clin Chem. 1982;28:1113–9.

    PubMed  CAS  Google Scholar 

  20. 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.

    Article  PubMed  CAS  Google Scholar 

  21. Raper CGL, Rosen C, Choudhury M. Automated red cell indices and marrow iron reserves in geriatric patients. J Clin Pathol. 1977;30:353–5.

    PubMed  CAS  Google Scholar 

  22. 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.

    PubMed  CAS  Google Scholar 

  23. Barnett MD, Gordon YB, Amess JAL, Mollin DL. Measurement of ferritin in serum by radioimmunoassay. J Clin Pathol. 1978;31:742–8.

    PubMed  CAS  Google Scholar 

  24. 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.

    PubMed  CAS  Google Scholar 

  25. 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.

    PubMed  CAS  Google Scholar 

  26. 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.

    Article  PubMed  CAS  Google Scholar 

  27. 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.

    PubMed  CAS  Google Scholar 

  28. Baynes RD, Bothwell TH, Bezwoda WR, et al. Hematologic and iron-related measurements in rheumatoid arthritis. Am J Clin Pathol. 1987;87:196–200.

    PubMed  CAS  Google Scholar 

  29. 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.

    PubMed  CAS  Google Scholar 

  30. 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.

    PubMed  CAS  Google Scholar 

  31. 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.

    Article  PubMed  CAS  Google Scholar 

  32. Lindstedt G, Lundberg P, Bjorn-Rasmussen E, Magnussen B. Serum-ferritin and iron-deficiency anaemia in hospital patients. Lancet. 1980;1:205–6.

    Article  PubMed  CAS  Google Scholar 

  33. Ballas SK. Normal serum iron and elevated total iron-binding capacity in iron-deficiency states. Am J Clin Pathol. 1979;71:401–3.

    PubMed  CAS  Google Scholar 

  34. 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.

    Google Scholar 

  35. 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.

    Google Scholar 

  36. 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.

    Google Scholar 

  37. 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.

    PubMed  CAS  Google Scholar 

  38. Puolakka J. Serum ferritin in the evaluation of iron status in young healthy women. Acta Obstet Gynecol Scand. 1980;95(suppl):S35-S41.

    Google Scholar 

  39. 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.

    PubMed  CAS  Google Scholar 

  40. Patterson C, Turpie ID, Benger AM. Assessment of iron stores in anemic geriatric patients. J Am Geriatr Soc. 1985;33:764–7.

    PubMed  CAS  Google Scholar 

  41. Blumberg AB, Marti HRM, Graber CG. Serum ferritin and bone marrow iron in patients undergoing continuous ambulatory peritoneal dialysis. JAMA. 1983;250:3317–9.

    Article  PubMed  CAS  Google Scholar 

  42. Sharma JC, Roy SN. Value of serum ferritin as an index of iron deficiency in elderly anaemic patients. Age Ageing. 1984;13:248–50.

    Article  PubMed  CAS  Google Scholar 

  43. 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.

    PubMed  CAS  Google Scholar 

  44. 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.

    PubMed  CAS  Google Scholar 

  45. 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.

    PubMed  CAS  Google Scholar 

  46. Kalmin ND, Bobson EB, Bettigole RE. Serum ferritin and marrow iron stores. N Y State J Med. 1978;78:1052–5.

    PubMed  CAS  Google Scholar 

  47. Smith RJ, Davis P, Thomson BR, et al. Serum ferritin levels in the anemia of rheumatoid arthritis. J Rheumatol. 1977;4(suppl):S389-S392.

    Google Scholar 

  48. 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.

    Article  PubMed  CAS  Google Scholar 

  49. McLaren GD, Carpenter JT, Nino HV. Erythrocyte protoporphyrin in the detection of iron deficiency. Clin Chem. 1975;21:1121–7.

    PubMed  CAS  Google Scholar 

  50. Sorbie J, Valberg LS, Corbett WEN, Ludwig J. Serum ferritin, cobalt excretion and body iron status. Can Med Assoc J. 1975;112:1173–8.

    PubMed  CAS  Google Scholar 

  51. 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.

    PubMed  CAS  Google Scholar 

  52. Wachtel TJ, Reuben DB, Fulton JP, Wartman SA. The use of “range of uncertainty.” Med Decis Making. 1985;5:325–34.

    Article  PubMed  CAS  Google Scholar 

  53. Charache S, Gittelsohn AM, Allen H, et al. Noninvasive assessment of tissue iron stores. Am J Clin Pathol. 1987;88:333–7.

    PubMed  CAS  Google Scholar 

  54. Paine CJ, Polk A, Eichner ER. Analysis of anemia in medical inpatients. Am J Med Sci. 1974;268:37–44.

    Article  PubMed  CAS  Google Scholar 

  55. Bentley DP, Williams P. Serum ferritin concentration as an index of storage iron in rheumatoid arthritis. J Clin Pathol. 1974;27:786–8.

    PubMed  CAS  Google Scholar 

  56. Child Ja, Brozovic B, Dyer NH, et al. The diagnosis of iron deficiency in patients with Crohn’s disease. Gut. 1973;14:642–8.

    PubMed  CAS  Google Scholar 

  57. 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.

    PubMed  CAS  Google Scholar 

  58. 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.

    PubMed  CAS  Google Scholar 

  59. Oluboyede OA. Iron studies in pregnant and non-pregnant women with haemoglobin SS or SC disease. Br J Obstet Gynaecol. 1980;87:989–95.

    PubMed  CAS  Google Scholar 

  60. 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.

    Article  Google Scholar 

  61. Gokal R, Millard PR, Weatherall DJ, et al. Iron metabolism in haemodialysis patients. Q J Med. 1979;48:369–91.

    PubMed  CAS  Google Scholar 

  62. 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.

    PubMed  CAS  Google Scholar 

  63. England JM, Ward SM, Down MC. Microcytosis, anisocytosis and the red cell indices in iron deficiency. Br J Haematol. 1976;34:589–97.

    PubMed  CAS  Google Scholar 

  64. Bartels U, Pederson NS, Jarnum S. Iron absorption and serum ferritin in chronic inflammatory bowel disease. Scand J Gastorenterol. 1978;13:649–56.

    Article  CAS  Google Scholar 

  65. 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.

    Article  PubMed  CAS  Google Scholar 

  66. Witte DL, Dick F, Goeken J, et al. C-reactive protein aids interpretation of serum ferritin. Clin Chem. 1985;31:1011.

    Google Scholar 

  67. Nelson R, Chawla M, Connolly P, LaPorte J. Ferritin as an index of bone marrow iron stores. South Med J. 1978;71:1482–4.

    PubMed  CAS  Google Scholar 

  68. 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.

    Article  CAS  Google Scholar 

  69. Wohlenberg H, Panitz N, Wacheck W. Hypoferramie und serumferritin. Dtsch Med Wochenschr. 1980;105:1527–30.

    Article  PubMed  CAS  Google Scholar 

  70. Leyland MJ, Ganguli PC, Blower D, Delamore IW. Immunoradiometric assay for ferritin in human serum. Scand J Haematol. 1975;14:385–92.

    Article  PubMed  CAS  Google Scholar 

  71. Guyatt GH, Patterson C, Ali M, et al. Diagnosis of iron deficiency anemia in the elderly. Am J Med. 1990;88:205–9.

    Article  PubMed  CAS  Google Scholar 

  72. Mulrow CD. The medical review article: state of the science. Ann Intern Med. 1987;106:485–8.

    PubMed  CAS  Google Scholar 

  73. 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.

    CAS  Google Scholar 

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Authors and Affiliations

  1. the Department of Medicine, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada

    Gordon H. Guyatt MD, Mahmoud Ali MD & Christopher Patterson MD

  2. the Department of Clinical Epidemiology and Biostatistics, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada

    Gordon H. Guyatt MD, Andrew D. Oxman MD, Andrew Willan PhD & William McIlroy PhD

  3. the Department of Family Medicine, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada

    Andrew D. Oxman MD

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  1. Gordon H. Guyatt MD
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  2. Andrew D. Oxman MD
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  3. Mahmoud Ali MD
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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.

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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

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