Laboratory methodologies for indicators of iron status: Strengths, limitations, and analytical challenges

American Journal of Clinical Nutrition

Volumn 106, Issue , 2017, Pages 1606S-1614S

  Pfeiffer, Christine M ^a   Looker, Anne C ^b  

^a NATIONAL CENTER FOR ENVIRONMENTAL HEALTH   (United States)

^b NATIONAL CENTER FOR HEALTH STATISTICS   (United States)

Author keywords

ferritin; Iron analysis; iron methodologies; NHANES; soluble transferrin receptor; total body iron

Indexed keywords

IRON; BIOLOGICAL MARKER; FERRITIN; TRANSFERRIN RECEPTOR;

CONFERENCE PAPER; HEALTH STATUS INDICATOR; HUMAN; LABORATORY; NUTRITIONAL STATUS; BLOOD; NUTRITION; NUTRITIONAL ASSESSMENT;

BIOMARKERS; FERRITINS; HUMANS; IRON; NUTRITION ASSESSMENT; NUTRITION SURVEYS; NUTRITIONAL STATUS; RECEPTORS, TRANSFERRIN;

EID: 85037607390     PISSN: 00029165     EISSN: 19383207     Source Type: Journal    
DOI: 10.3945/ajcn.117.155887     Document Type: Conference Paper

References (79)

1. Raiten DJ, Namaste S, Brain B, Combs G Jr., L'Abbe MR, Wasantwisut E, Darnton-Hill I. Executive summary-biomarkers of nutrition for development: building a consensus. Am J Clin Nutr 2011; 94:633S-50S.
2. Hastka J, Lasserre JJ, Schwarzbeck A, Reiter A, Hehlmann R. Laboratory tests of iron status: correlation or common sense? Clin Chem 1996;42:718-24.
3. Worwood M. Indicators of the iron status of populations: ferritin. In: WHO, editor. Assessing the iron status of populations: including literature reviews: report of a Joint World Health Organization/Centers for Disease Control and Prevention Technical Consultation on the Assessment of Iron Status at the Population Level, Geneva, Switzerland, 6-8 April 2004. 2nd ed. Geneva (Switzerland): WHO; 2007.
4. Beard J. Indicators of the iron status of populations: free erythrocyte protoporphyrin and zinc protoporphyrin; serum and plasma iron, total iron binding capacity and transferrin saturation; and serum transferrin receptor. In: WHO, editor. Assessing the iron status of populations: including literature reviews: report of a Joint World Health Organization/Centers for Disease Control and Prevention Technical Consultation on the Assessment of Iron Status at the Population Level, Geneva, Switzerland, 6-8 April 2004. 2nd ed. Geneva (Switzerland): WHO; 2007.
5. Lynch S. Indicators of the iron status of populations: red blood cell parameters. In: WHO, editor. Assessing the iron status of populations: including literature reviews: report of a Joint World Health Organization/Centers for Disease Control and Prevention Technical Consultation on the Assessment of Iron Status at the Population Level, Geneva, Switzerland, 6-8 April 2004. 2nd ed. Geneva (Switzerland): WHO; 2007.
6. Raiten DJ, Sakr Ashour FA, Ross AC, Meydani SN, Dawson HD, Stephensen CB, Brabin BJ, Suchdev PS, van Ommen B. Inflammation and Nutritional Science for Programs/Policies and Interpretation of Research Evidence (INSPIRE). J Nutr 2015;145:1039S-108S.
7. Weiss G, Goodnough LT. Anemia of chronic disease. N Engl J Med 2005;352:1011-23.
8. European Association for the Study of the Liver. EASL clinical practice guidelines for HFE hemochromatosis. J Hepatol 2010;53:3-22.
9. Bacon BR, Adams PC, Kowdley KV, Powell LW, Tavill AS; American Association for the Study of Liver Diseases. Diagnosis and management of hemochromatosis: 2011 practice guideline by the American Association for the Study of Liver Diseases. Hepatology 2011;54:328-43.
10. Adams PC, Kertesz AE, McLaren CE, Barr R, Bamford A, Chakrabarti S. Population screening for hemochromatosis: a comparison of unbound iron-binding capacity, transferrin saturation, and C282Y genotyping in 5,211 voluntary blood donors. Hepatology 2000;31:1160-4.
11. Adams PC, Reboussin DM, Press RD, Barton JC, Acton RT, Moses GC, Leiendecker-Foster C, McLaren GD, Dawkins FW, Gordeuk VR, et al. Biological variability of transferrin saturation and unsaturated iron-binding capacity. Am J Med 2007;120:999.e1-7.
12. Metzgeroth G, Schultheis B, Dorn-Beineke A, Hehlmann R, Hastka J. Zinc protoporphyrin, a useful parameter to address hyperferritinemia. Ann Hematol 2007;86:363-8.
13. Ahluwalia N, Lammi-Keefe CJ, Haley NR, Beard JL. Day-to-day variation in iron-status indexes in elderly women. Am J Clin Nutr 1993;57:414-9.
14. Lacher DA, Hughes JP, Carroll MD. Biological variation of laboratory analytes based on the 1999-2002 National Health and Nutrition Examination Survey. Natl Health Stat Rep 2010:1-7.
15. Ricós C, Alvarez V, Cava F, García-Lario JV, Hernández A, Jiménez CV, Minchinela J, Perich C, Simón M. Current databases on biological variation: pros, cons and progress. Scand J Clin Lab Invest 1999;59:491-500.
16. Cooper MJ, Zlotkin SH. Day-to-day variation of transferrin receptor and ferritin in healthy men and women. Am J Clin Nutr 1996;64:738-42.
17. Dale JC, Burritt MF, Zinsmeister AR. Diurnal variation of serum iron, iron-binding capacity, transferrin saturation, and ferritin levels. Am J Clin Pathol 2002;117:802-8.
18. Pearce CJ, Bosomworth MP. Storage of heparinized blood. Ann Clin Biochem 1991;28:112.
19. van Eijsden M, van der Wal MF, Hornstra G, Bonsel GJ. Can wholeblood samples be stored over 24 hours without compromising stability of C-reactive protein, retinol, ferritin, folic acid, and fatty acids in epidemiologic research? Clin Chem 2005;51:230-2.
20. Drammeh BS, Schleicher RL, Pfeiffer CM, Jain RB, Zhang M, Nguyen PH. Effects of delayed sample processing and freezing on serum concentrations of selected nutritional indicators. Clin Chem 2008;54:1883-91.
21. Wilding P, Zilva JF, Wilde CE. Transport of specimens for clinical chemistry analysis. Ann Clin Biochem 1977;14:301-6.
22. Jansen EH, Beekhof PK, Schenk E. Long-term stability of biomarkers of the iron status in human serum and plasma. Biomarkers 2013;18:365-8.
23. Whitehead RD Jr., Zhang M, Sternberg MR, Schleicher RL, Drammeh B, Mapango C, Pfeiffer CM. Effects of preanalytical factors on hemoglobin measurement: a comparison of two HemoCue point-ofcare analyzers. Clin Biochem 2017;50:513-20.
24. Blanck HM, Pfeiffer CM, Caudill SP, Reyes M, Gunter EW, Imperatore G, van Assendelft OW, Strider S, Dearth T. Serum iron and iron-binding capacity: a round-robin interlaboratory comparison study. Clin Chem 2003;49:1672-5.
25. Blackmore S, Hamilton M, Lee A, Worwood M, Brierley M, Heath A, Thorpe SJ. Automated immunoassay methods for ferritin: recovery studies to assess traceability to an international standard. Clin Chem Lab Med 2008;46:1450-7.
26. Thorpe SJ, Heath A, Sharp G, Cook J, Ellis R, Worwood M. A WHO reference reagent for the Serum Transferrin Receptor (sTfR): international collaborative study to evaluate a recombinant soluble transferrin receptor preparation. Clin Chem Lab Med 2010;48:815-20.
27. Thorpe SJ. The development and role of international biological reference materials in the diagnosis of anaemia. Biologicals 2010;38: 449-58.
28. Skikne BS, Flowers CH, Cook JD. Serum transferrin receptor: a quantitative measure of tissue iron deficiency. Blood 1990;75:1870-6.
29. Flowers CH, Skikne BS, Covell AM, Cook JD. The clinical measurement of serum transferrin receptor. J Lab Clin Med 1989;114:368-77.
30. Pfeiffer CM, Cook JD, Mei Z, Cogswell ME, Looker AC, Lacher DA. Evaluation of an automated soluble transferrin receptor (sTfR) assay on the Roche Hitachi analyzer and its comparison to two ELISA assays. Clin Chim Acta 2007;382:112-6.
31. Cook JD, Flowers CH, Skikne BS. The quantitative assessment of body iron. Blood 2003;101:3359-64.
32. Looker AC, Dallman PR, Carroll MD, Gunter EW, Johnson CL. Prevalence of iron deficiency in the United States. JAMA 1997;277:973-6.
33. Simmons WK, Cook JD, Bingham KC, Thomas M, Jackson J, Jackson M, Ahluwalia N, Kahn SG, Patterson AW. Evaluation of a gastric delivery system for iron supplementation in pregnancy. Am J Clin Nutr 1993;58:622-6.
34. Thuy PV, Berger J, Davidsson L, Khan NC, Lam NT, Cook JD, Hurrell RF, Khoi HH. Regular consumption of NaFeEDTA-fortified fish sauce improves iron status and reduces the prevalence of anemia in anemic Vietnamese women. Am J Clin Nutr 2003;78:284-90.
35. Engle-Stone R, Nankap M, Ndjebayi AO, Erhardt JG, Brown KH. Plasma ferritin and soluble transferrin receptor concentrations and body iron stores identify similar risk factors for iron deficiency but result in different estimates of the national prevalence of iron deficiency and iron-deficiency anemia among women and children in Cameroon. J Nutr 2013;143:369-77.
36. Cogswell ME, Looker AC, Pfeiffer CM, Cook JD, Lacher DA, Beard JL, Lynch SR, Grummer-Strawn LM. Assessment of iron deficiency in US preschool children and nonpregnant females of childbearing age: National Health and Nutrition Examination Survey 2003-2006. Am J Clin Nutr 2009;89:1334-42.
37. Mei Z, Cogswell ME, Looker AC, Pfeiffer CM, Cusick SE, Lacher DA, Grummer-Strawn LM. Assessment of iron status in US pregnant women from the National Health and Nutrition Examination Survey (NHANES), 1999-2006. Am J Clin Nutr 2011;93:1312-20.
38. Gupta PM, Perrine CG, Mei Z, Scanlon KS. Iron, anemia, and iron deficiency anemia among young children in the United States. Nutrients 2016:8:E330.
39. Ronnenberg AG, Wood RJ, Wang X, Xing H, Chen C, Chen D, Guang W, Huang A, Wang L, Xu X. Preconception hemoglobin and ferritin concentrations are associated with pregnancy outcome in a prospective cohort of Chinese women. J Nutr 2004;134:2586-91.
40. Akesson A, Bjellerup P, Berglund M, Bremme K, Vahter M. Soluble transferrin receptor: longitudinal assessment from pregnancy to postlactation. Obstet Gynecol 2002;99:260-6.
41. van den Broek NR, Letsky EA, White SA, Shenkin A. Iron status in pregnant women: which measurements are valid? Br J Haematol 1998; 103:817-24.
42. Grant FK, Martorell R, Flores-Ayala R, Cole CR, Ruth LJ, Ramakrishnan U, Suchdev PS. Comparison of indicators of iron deficiency in Kenyan children. Am J Clin Nutr 2012;95:1231-7.
43. Punnonen K, Irjala K, Rajamaki A. Serum transferrin receptor and its ratio to serum ferritin in the diagnosis of iron deficiency. Blood 1997; 89:1052-7.
44. Skikne BS, Punnonen K, Caldron PH, Bennett MT, Rehu M, Gasior GH, Chamberlin JS, Sullivan LA, Bray KR, Southwick PC. Improved differential diagnosis of anemia of chronic disease and iron deficiency anemia: a prospective multicenter evaluation of soluble transferrin receptor and the sTfR/log ferritin index. Am J Hematol 2011;86:923-7.
45. Berlin T, Meyer A, Rotman-Pikielny P, Natur A, Levy Y. Soluble transferrin receptor as a diagnostic laboratory test for detection of iron deficiency anemia in acute illness of hospitalized patients. Isr Med Assoc J 2011;13:96-8.
46. Girelli D, Nemeth E, Swinkels DW. Hepcidin in the diagnosis of iron disorders. Blood 2016;127:2809-13.
47. Ganz T. Hepcidin and iron regulation, 10 years later. Blood 2011;117: 4425-33.
48. Donker AE, Raymakers RA, Vlasveld LT, van Barneveld T, Terink R, Dors N, Brons PP, Knoers NV, Swinkels DW. Practice guidelines for the diagnosis and management of microcytic anemias due to genetic disorders of iron metabolism or heme synthesis. Blood 2014;123: 3873-86.
49. Kroot JJ, Tjalsma H, Fleming RE, Swinkels DW. Hepcidin in human iron disorders: diagnostic implications. Clin Chem 2011;57:1650-69.
50. Nemeth E, Valore EV, Territo M, Schiller G, Lichtenstein A, Ganz T. Hepcidin, a putative mediator of anemia of inflammation, is a type II acute-phase protein. Blood 2003;101:2461-3.
51. Pak M, Lopez MA, Gabayan V, Ganz T, Rivera S. Suppression of hepcidin during anemia requires erythropoietic activity. Blood 2006;108:3730-5.
52. Murphy AT, Witcher DR, Luan P, Wroblewski VJ. Quantitation of hepcidin from human and mouse serum using liquid chromatography tandem mass spectrometry. Blood 2007;110:1048-54.
53. van der Vorm LN, Hendriks JC, Laarakkers CM, Klaver S, Armitage AE, Bamberg A, Geurts-Moespot AJ, Girelli D, Herkert M, Itkonen O, et al. Toward worldwide hepcidin assay harmonization: identification of a commutable secondary reference material. Clin Chem 2016;62:993-1001.
54. Brissot P, Ropert M, Le Lan C, Loréal O. Non-transferrin bound iron: a key role in iron overload and iron toxicity. Biochim Biophys Acta 2012;1820:403-10.
55. Cabantchik ZI. Labile iron in cells and body fluids: physiology, pathology, and pharmacology. Front Pharmacol 2014;5:45.
56. Jacobs EM, Hendriks JC, van Tits BL, Evans PJ, Breuer W, Liu DY, Jansen EH, Jauhiainen K, Sturm B, Porter JB, et al. Results of an international round robin for the quantification of serum non-transferrinbound iron: need for defining standardization and a clinically relevant isoform. Anal Biochem 2005;341:241-50.
57. de Swart L, Hendriks JC, van der Vorm LN, Cabantchik ZI, Evans PJ, Hod EA, Brittenham GM, Furman Y, Wojczyk B, Janssen MC, et al. Second international round robin for the quantification of serum nontransferrin-bound iron and labile plasma iron in patients with ironoverload disorders. Haematologica 2016;101:38-45.
58. Ito S, Ikuta K, Kato D, Shibusa K, Niizeki N, Tanaka H, Addo L, Toki Y, Hatayama M, Inamura J, et al. Non-transferrin-bound iron assay system utilizing a conventional automated analyzer. Clin Chim Acta 2014;437:129-35.
59. Piva E, Brugnara C, Spolaore F, Plebani M. Clinical utility of reticulocyte parameters. Clin Lab Med 2015;35:133-63.
60. Baker RD, Greer FR. Diagnosis and prevention of iron deficiency and iron-deficiency anemia in infants and young children (0-3 years of age). Pediatrics 2010;126:1040-50.
61. Ratcliffe LE, Thomas W, Glen J, Padhi S, Pordes BA, Wonderling D, Connell R, Stephens S, Mikhail AI, Fogarty DG, et al. Diagnosis and management of iron deficiency in CKD: a summary of the NICE guideline recommendations and their rationale. Am J Kidney Dis 2016;67:548-58.
62. Hollowell JG, van Assendelft OW, Gunter EW, Lewis BG, Najjar M, Pfeiffer C. Hematological and iron-related analytes-reference data for persons aged 1 year and over: United States, 1988-94. Vital Health Stat 11 2005:1-156.
63. CDC, National Center for Environmental Health. Second national report on biochemical indicators of diet and nutrition in the US population [Internet]. c2012. [cited 2016 Jun 23]. Available from: http://www.cdc.gov/nutritionreport/.
64. CDC, National Center for Health Statistics. National Health and Nutrition Examination Survey. 2009-2010 Lab methods [Internet]. [cited 2016 Oct 5]. Available from: https://wwwn.cdc.gov/nchs/nhanes/continuousnhanes/labmethods.aspx?BeginYear=2009.
65. Summary of a report on assessment of the iron nutritional status of the United States population. Expert Scientific Working Group. Am J Clin Nutr 1985;42:1318-30.
66. CDC. Iron deficiency-United States, 1999-2000. MMWR Morb Mortal Wkly Rep 2002;51:897-9.
67. Cusick SE, Mei Z, Freedman DS, Looker AC, Ogden CL, Gunter E, Cogswell ME. Unexplained decline in the prevalence of anemia among US children and women between 1988-1994 and 1999-2002. Am J Clin Nutr 2008;88:1611-7.
68. Finch CA, Smith NJ, Cook JD, Labbe RF, Lipschitz DA. Laboratory parameters in the diagnosis of iron deficiency. Haematologia (Budap) 1974;8:177-82.
69. Cook JD, Finch CA, Smith NJ. Evaluation of the iron status of a population. Blood 1976;48:449-55.
70. Derman DP, Lynch SR, Bothwell TH, Charlton RW, Torrance JD, Brink BA. Serum ferritin as an index of iron nutrition in rural and urban South African children. Br J Nutr 1978;39:383-9.
71. Berger J, Dyck JL, Galan P, Aplogan A, Schneider D, Traissac P, Hercberg S. Effect of daily iron supplementation on iron status, cellmediated immunity, and incidence of infections in 6-36 month old Togolese children. Eur J Clin Nutr 2000;54:29-35.
72. Cook JD, Skikne BS, Lynch SR, Reusser ME. Estimates of iron sufficiency in the US population. Blood 1986;68:726-31.
73. Hallberg L, Bengtsson C, Lapidus L, Lindstedt G, Lundberg PA, Hulten L. Screening for iron deficiency: an analysis based on bonemarrow examinations and serum ferritin determinations in a population sample of women. Br J Haematol 1993;85:787-98.
74. Guyatt GH, Oxman AD, Ali M, Willan A, McIlroy W, Patterson C. Laboratory diagnosis of iron-deficiency anemia: an overview. J Gen Intern Med 1992;7:145-53.
75. WHO, CDC. Assessing the iron status of populations: including literature reviews. Report of a Joint World Health Organization/Centers for Disease Control and Prevention Technical Consultation on the Assessment of Iron Status at the Population Level, Geneva, Switzerland, 6-8 April 2004. 2nd ed. Geneva (Switzerland): WHO/CDC; 2007.
76. US Department of Health and Human Services. Healthy People 2010: understanding and improving health. 2nd ed. Washington (DC): US Department of Health and Human Services; 2000.
77. Cook JD, Boy E, Flowers C, Daroca Mdel C. The influence of highaltitude living on body iron. Blood 2005;106:1441-6.
78. Means RT Jr., Allen J, Sears DA, Schuster SJ. Serum soluble transferrin receptor and the prediction of marrow aspirate iron results in a heterogeneous group of patients. Clin Lab Haematol 1999;21:161-7.
79. USPSTF. Iron deficiency anemia in pregnant women: screening and supplementation [Internet]. c2015 [cited 2016 Oct 4]. Available from: https://www.uspreventiveservicestaskforce.org/Page/Document/Update-SummaryFinal/iron-deficiency-Anemia-in-pregnant-women-screeningand-supplementation.