Guideline for the laboratory diagnosis of functional iron deficiency

British Journal of Haematology

Volumn 161, Issue 5, 2013, Pages 639-648

  Thomas, D Wayne ^a   Hinchliffe, Rod F ^b   Briggs, Carol ^c   Macdougall, Iain C ^d   Littlewood, Tim ^e   Cavill, Ivor ^f  

^a DERRIFORD HOSPITAL   (United Kingdom)

^b SHEFFIELD CHILDREN S HOSPITAL   (United Kingdom)

^c UNIVERSITY COLLEGE HOSPITAL   (United Kingdom)

^d KING S COLLEGE HOSPITAL   (United Kingdom)

^e JOHN RADCLIFFE HOSPITAL   (United Kingdom)

^f Washington Medical School   (United Kingdom)

Author keywords

Anaemia; Functional studies; Iron deficiency; Laboratory haematology

Indexed keywords

ERYTHROPOIETIN; FERRITIN; HEPCIDIN; IRON; PROTOPORPHYRIN ZINC; TRANSFERRIN RECEPTOR;

ANEMIA OF CHRONIC DISEASE; ARTICLE; BLOOD CYTOLOGY; BONE MARROW EXAMINATION; CHRONIC DISEASE; CLINICAL EFFECTIVENESS; DISEASE ASSOCIATION; FERRITIN BLOOD LEVEL; FUNCTIONAL IRON DEFICIENCY; HEMATOLOGICAL PARAMETERS; HUMAN; IMMATURE RETICULOCYTE FRACTION; IRON BINDING CAPACITY; IRON DEFICIENCY; IRON STORAGE; IRON THERAPY; LABORATORY DIAGNOSIS; MEAN CELL HEMOGLOBIN; MEAN CELL VOLUME; PERCENTAGE OF HYPOCHROMIC RED CELL; PERCENTAGE SATURATION VALUE; PRACTICE GUIDELINE; PRIORITY JOURNAL; QUALITY CONTROL; RED BLOOD CELL SIZE FACTOR; RETICULOCYTE COUNT; RETICULOCYTE HEMOGLOBIN CONTENT;

ANEMIA, IRON-DEFICIENCY; ANTIMICROBIAL CATIONIC PEPTIDES; BIOLOGICAL MARKERS; BLOOD SPECIMEN COLLECTION; CLINICAL LABORATORY TECHNIQUES; ERYTHROPOIETIN; HUMANS; IRON; RECEPTORS, TRANSFERRIN;

EID: 84877794434     PISSN: 00071048     EISSN: 13652141     Source Type: Journal    
DOI: 10.1111/bjh.12311     Document Type: Article

References (76)

1. Ali, M., Fayemi, A.O., Rigolosi, R., Frascino, J., Marsden, T. & Malcolm, D. (1980) Hemosiderosis in hemodialysis patients. An autopsy study of 50 cases. Journal of the American Medical Association, 244, 343-345.
2. Ali, M., Rigolosi, R., Fayemi, A.O., Braun, E.V., Frascino, J. & Singer, R. (1982) Failure of serum ferritin levels to predict bone-marrow iron content after intravenous iron-dextran therapy. Lancet, 1, 652-655.
3. Arndt, U., Kaltwasser, J.P., Gottschalk, R., Hoelzer, D. & Moller, B. (2005) Correction of iron-deficient erythropoiesis in the treatment of anemia of chronic disease with recombinant human erythropoietin. Annals of Hematology, 84, 159-166.
4. Barron, B.A., Hoyer, J.D. & Tefferi, A. (2001) A bone marrow report of absent stainable iron is not diagnostic of iron deficiency. Annals of Hematology, 80, 66-169.
5. Brugnara, C. (2003) Iron deficiency and erythropoiesis: new diagnostic approaches. Clinical Chemistry, 49, 1573-1578.
6. Brugnara, C., Schiller, B. & Moran, J. (2006) Reticulocyte haemoglobin content (Ret He) and assessment of iron-deficient states. Clinical and Laboratory Haematology, 28, 303-308.
7. Buhrmann, E., Mentzer, W.C. & Lubin, B.H. (1978) The influence of plasma bilirubin on zinc protoporphyrin measurement by a hematofluorimeter. Journal of Laboratory and Clinical Medicine, 91, 710-716.
8. Buttarello, M., Pajola, R., Novello, E., Rebeschini, M., Cantaro, S., Oliosi, F., Naso, A. & Plebani, M. (2010) Diagnosis of iron deficiency in patients undergoing hemodialysis. American Journal of Clinical Pathology, 133, 949-954.
9. Canals, C., Remacha, A.F., Sarda, M.P., Piazuelo, J.M., Royo, M.T. & Romero, M.A. (2005) Clinical utility of the new Sysmex XE2100 parameter - reticulocyte hemoglobin equivalent - in the diagnosis of anemia. Hematologica, 90, 1133-1134.
10. Cavill, I. (1999) Iron status as measured by serum ferritin: the marker and its limitations. American Journal of Kidney Disease, 34 (Suppl. 2), S12-S17.
11. Cazzola, M., Ponchio, L., Beguin, Y., Rosti, V., Bergamaschi, G., Liberato, N.L., Fregoni, V., Nalli, G., Barosi, G. & Ascari, E. (1992) Subcutaneous erythropoietin for treatment of refractory anemia in hematologic disorders. Results of a phase I/II clinical trial. Blood, 79, 29-37.
12. Chen, Y.C., Hung, S.C. & Tarng, D.C. (2006) Association between transferrin receptor-ferritin index and conventional measures of iron responsiveness in hemodialysis patients. American Journal of Kidney Disease, 47, 1036-1044.
13. Chiang, W.C., Tsai, T.J., Chen, Y.M., Lin, S.L. & Hsieh, B.S. (2002) Serum soluble transferrin receptor reflects erythropoiesis but not iron availability in erythropoietin-treated chronic hemodialysis patients. Clinical Nephrology, 58, 363-369.
14. Chuang, C.L., Liu, R.S., Wei, Y.H., Huang, T.P. & Tarng, D.C. (2003) Early prediction of response to intravenous iron supplementation by reticulocyte hemoglobin content and high-fluorescence reticulocyte count in hemodialysis patients. Nephrology Dialysis Transplantation, 18, 370-377.
15. Cook, J.D. & Skikne, B.S. (1982) Serum ferritin: a possible model for the assessment of nutrient stores. American Journal of Clinical Nutrition, 35, S1180-S1185.
16. Coyne, D.W. (2011) Hepcidin: clinical utility as a diagnostic tool and therapeutic target. Kidney International, 80, 240-244.
17. Coyne, D.W., Kapoian, T., Suki, W., Singh, A.K., Moran, J.E., Dahl, N.V. & Rizkala, A.R. (2007) Ferric gluconate is highly efficacious in anemic hemodialysis patients with high serum ferritin and low transferrin saturation: results of the Dialysis Patients' Response to IV iron with Elevated Ferritin (DRIVE) study. Journal of the American Society of Nephrology, 18, 975-984.
18. Davies, B.H. (1996) Immature reticulocyte fraction (IRF): by any name a useful clinical parameter. Laboratory Hematology, 2, 2-8.
19. Dukkipati, R. & Kalantar-Zadeh, K. (2007) Should we limit the ferritin upper threshold to 500 ng/ml in CKD patients? Nephrology News Issues, 21, 34-38.
20. Ferguson, B.J., Skikne, B.S., Simpson, K.M., Baynes, R.D. & Cook, J.D. (1992) Serum transferrin receptor distinguishes the anemia of chronic disease from iron deficiency anemia. Journal of Laboratory and Clinical Medicine, 119, 385-390.
21. Fernandez-Rodriguez, A.M., Guindeo-Casasus, M.C., Molero-Labarta, T., Dominguez-Cabrera, C., Hortal-Casc n, L., Perez-Borges, P., Vega-Diaz, N., Saavedra-Santana, P. & Palop-Cubillo, L. (1999) Diagnosis of iron deficiency in chronic renal failure. American Journal of Kidney Disease, 34, 508-513.
22. Fishbane, S. & Maessaka, J.K. (1997) Iron management in end-stage renal failure. American Journal of Kidney Disease, 29, 319-333.
23. Fishbane, S., Shapiro, W., Dutka, P., Valenzuela, O.F. & Faubert, J. (2001) A randomised trial of iron deficiency testing strategies in haemodialysis patients. Kidney International, 60, 2406-2411.
24. Ganz, T. (2007) Molecular control of iron transport. Journal of the American Society of Nephrology, 18, 394-400.
25. Garrett, S. & Worwood, M. (1994) Zinc protoporphyrin and iron-deficient erythropoiesis. Acta Haematologica, 91, 21-25.
26. Garzia, M., Di Mario, A., Ferraro, E., Tazza, L., Rossi, E., Luciani, G. & Zini, G. (2007) Reticulocyte haemoglobin equivalent: an indicator of reduced iron availability in chronic kidney diseases during erythropoietin therapy. Laboratory Hematology, 13, 6-11.
27. Goodnough, L.T., Nemeth, E. & Ganz, T. (2011) Detection, evaluation and management of iron-restricted erythropoiesis. Blood, 116, 4754-4761.
28. Graham, E.A., Felgenhauer, J., Detter, J.C. & Labbe, R.F. (1996) Elevated zinc protoporphyrin associated with thalassemia trait and hemoglobin E. Journal of Pediatrics, 129, 105-110.
29. Henry, D.H. Parenteral iron therapy in cancer-associated anemia (2010). Hematology American Society of Hematology Education Program, Haematology, 2010, 351-356.
30. Henry, D.H., Brooks, B.J. Jr, Case, D.C. Jr, Fishkin, E., Jacobson, R., Keller, A.M., Kugler, J., Moore, J., Silver, R.T., Storniolo, A.M., Abels, R.I., Gordon, D.S., Nelson, R., Larholt, K., Bryant, E. & Rudnick, S. (1995) Recombinant human erythropoietin therapy for anemic cancer patients receiving cisplatin therapy. Cancer Journal Scientific American, 1, 252-260.
31. Hochberg, M.C., Arnold, C.M., Hogans, B.B. & Spivak, J.L. (1988) Serum immunoreactive erythropoietin in rheumatoid arthritis: impaired response to anemia. Arthritis and Rheumatism, 31, 1318-1321.
32. Huebers, H.A., Beguin, Y., Pootrakul, P., Einspahr, D. & Finch, C.A. (1990) Intact transferrin receptors in human plasma and their relation to erythropoiesis. Blood, 75, 102-107.
33. Hughes, D.A., Stuart-Smith, S.E. & Bain, B.J. (2004) How should stainable iron in bone marrow films be assessed? Journal of Clinical Pathology, 57, 1038-1040.
34. Kalantar-Zadeh, K., Regidor, D.L., McAllister, C.J., Michael, B. & Warnock, D.G. (2005) Time-dependent associations between iron and mortality in hemodialysis patients. Journal of the American Society of Nephrology, 16, 3070-3080.
35. KDIGO (Kidney Disease: Improving Global Outcomes) Anemia Work Group (2012) Clinical Practice Guideline for Anemia in Chronic Kidney Disease. Kidney International Supplements, 2, 283-287.
36. Kohgo, Y., Niitsu, Y., Kondo, H., Kato, J., Tsushima, N., Sasaki, K., Hirayama, M., Numata, T., Nishisato, T. & Urushizaki, I. (1987) Serum transferrin receptor as a new index of erythropoiesis. Blood, 70, 1955-1958.
37. Koulaouzidis, A., Said, E., Cottier, R. & Saeed, A.A. (2009) Soluble transferrin receptors and iron deficiency, a step beyond ferritin. A systematic review. Journal of Gastrointestinal and Liver Disease, 18, 345-352.
38. Lee, E.J., Oh, E.J., Park, Y.J., Lee, H.K. & Kim, B.K. (2002) Soluble transferrin receptor (sTfR) and sTfR/log ferritin index in anemic patients with nonhematologic malignancy and chronic inflammation. Clinical Chemistry, 48, 1118-1121.
39. Lippi, G., Salvagno, G.L., Solero, G.P., Franchini, M. & Guidi, G.C. (2005) Stability of blood cell counts, hematologic parameters and reticulocyte indexes on the Advia A120 hematologic analyser. Journal of Laboratory and Clinical Medicine, 146, 333-340.
40. Littlewood, T.J., Zagari, M., Pallister, C. & Perkins, A. (2003) Baseline and early treatment factors are not clinically useful for predicting individual response to erythropoietin in anemic cancer patients. Oncologist, 8, 99-107.
41. Ljung, T., Back, R. & Hellstrom-Lindberg, E. (2004) Hypochromic red blood cells in low-risk myelodysplastic syndromes: effects of treatment with hemopoietic growth factors. Haematologica, 89, 1446-1553.
42. Locatelli, F., Aljama, P., Barany, P., Canaud, B., Carrera, F., Eckardt, K.U., Horl, W.H., Macdougall, I.C., Macleod, A., Wiecek, A. & Cameron, S. European Best Practice Guidelines Working Group. (2004) Revised European best practice guidelines for the management of anaemia in patients with chronic renal failure. Nephrology Dialysis Transplantation, 19 (Suppl. 2):ii, 1-47.
43. Low, C.L., Bailie, G.R. & Eisele, G. (1997) Sensitivity and specificity of transferrin saturation and serum ferritin as markers of iron status after intravenous iron dextran in hemodialysis patients. Renal Failure, 19, 781-788.
44. Macdougall, I.C., Hutton, R.D., Cavill, I., Coles, G.A. & Williams, J.D. (1989) Poor response to treatment of renal anaemia with erythropoietin corrected by iron given intravenously. British Medical Journal, 299, 157-158.
45. Macdougall, I.C., Hutton, R.D., Cavill, I., Coles, G.A. & Williams, J.D. (1990) Treating renal anaemia with recombinant human erythropoietin: practical guidelines and a clinical algorithm. British Medical Journal, 300, 655-659.
46. Macdougall, I.C., Cavill, I., Hulme, B., Bain, B., McGregor, E., McKay, P., Sanders, E., Coles, G.A. & Williams, J.D. (1992) Detection of iron deficiency during erythropoietin treatment: a new approach. British Medical Journal, 304, 225-226.
47. Macdougall, I.C., Malyszko, J., Hider, R.C. & Bansal, S.S. (2010) Current status of the measurement of blood hepcidin levels in chronic kidney disease. Clinical Journal of the American Society of Nephrology, 5, 1681-1689.
48. Maconi, M., Cavalca, L., Danise, P., Cardarelli, F. & Brini, M. (2009) Erythrocyte and reticulocyte indices in iron deficiency in chronic kidney disease: comparison of two methods. Scandinavian Journal of Clinical and Laboratory Investigation, 69, 365-370.
49. Mast, A.E., Blinder, M.A., Gronowski, A.M., Chumley, C. & Scott, M.G. (1998) Clinical utility of the soluble transferrin receptor and comparison with serum ferritin in several populations. Clinical Chemistry, 44, 45-51.
50. Mast, A.E., Blinder, M.A., Lu, Q., Flax, S. & Dietzen, D.J. (2002) Clinical utility of the reticulocyte hemoglobin content in the diagnosis of iron deficiency. Blood, 99, 1489-1491.
51. Mast, A.E., Blinder, M.A. & Dietzen, D.J. (2008) Reticulocyte hemoglobin content. American Journal of Hematology, 83, 307-310.
52. Matzkies, F.K., Cullen, P., Schaefer, L., Hartmann, M., Hohage, H. & Schaefer, R.M. (1999) Zinc protoporphyrin and percentage of hypochromic erythrocytes as markers of functional iron deficiency during therapy with erythropoietin in patients with advanced acquired immunodeficiency syndrome. Southern Medical Journal, 92, 1157-1161.
53. Means, R.T., Allen, J., Sears, D.A. & Schuster, S.J. (1999) Serum soluble transferrin receptor and the prediction of marrow iron results in a heterogeneous group of patients. Clinical and Laboratory Haematology, 21, 161-167.
54. Miller, C.B., Jones, R.J., Piantadosi, S., Abeloff, M.D. & Spivak, J.L. (1990) Decreased erythropoietin response in patients with the anemia of cancer. New England Journal of Medicine, 322, 1689-1692.
55. Mittman, M., Sreedhara, R., Mushnick, R., Chattopadhyay, J., Zelmanovic, D., Vasghi, M. & Avram, M.M. (1997) Reticulocyte hemoglobin content predicts functional iron deficiency in hemodialysis patients receiving rHuEPO. American Journal of Kidney Disease, 30, 912-922.
56. Miwa, N., Akiba, T., Kimata, N., Hamaguchi, Y., Arakawa, Y., Tamura, T., Nitta, K. & Tsuchiya, K. (2010) Usefulness of measuring reticulocyte haemoglobin equivalent in the management of haemodialysis patients with iron deficiency. International Journal of Laboratory Haematology, 32, 248-255.
57. National Kidney Foundation (2002) KDOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. American Journal of Kidney Disease, 39 (Suppl. 1), S1-S266.
58. National Kidney Foundation (2006) KDOQI Clinical practice guidelines and clinical practice recommendations for anemia in chronic kidney disease. American Journal of Kidney Disease, 47(Suppl. 3), S11-S145.
59. Nemeth, E., Tuttle, M.S., Powelson, J., Vaughn, M.B., Donovan, A., Ward, D.M., Ganz, T. & Kaplan, J. (2004) Hepcidin regulates cellular iron reflux by binding to ferroportin and inducing its internalisation. Science, 306, 2090-2093.
60. NICE (2006) Anaemia Management in People With Chronic Kidney Disease. Clinical guideline 39. National Institute for Health and Clinical Excellence, London.
61. NICE (2011) Anaemia Management in People With Chronic Kidney Disease. Clinical guideline 114. National Institute for Health and Clinical Excellence, London.
62. Peters, H.P., Rumjon, A., Bansal, S.S., Laarakkers, C.M., van den Brand, J.A., Sarafidis, P., Musto, R., Malyszko, J., Swinkels, D.W., Wetzels, J.F. & Macdougall, I.C. (2012) Intra-individual variability of serum hepcidin-25 in haemodialysis patients using mass spectrometry and ELISA. Nephrology, Dialysis, Transplantation, 27, 3923-3929.
63. Punnonen, K., Irjala, K. & Rajamaki, A. (1997) Serum transferrin receptor and its ratio to serum ferritin in the diagnosis of iron deficiency. Blood, 89, 1052-1057.
64. Qunibi, W.Y., Martinez, C., Smith, M., Benjamin, J., Mangione, A. & Roger, S.D. (2010) A randomised controlled trial comparing intravenous ferric carboxymaltose with oral iron for the treatment of iron deficiency of non-dialysis dependent chronic kidney disease patients. Nephrology Dialysis Transplantation, 10, 1-9.
65. Rose, E.H., Abels, R.I., Nelson, R.A., McCullough, D.M. & Lessin, L. (1995) The use of rHuEPO in the treatment of anaemia related to myelodysplasia (MDS). British Journal of Haematology, 89, 831-837.
66. Tessitore, N., Solero, G.P., Lippi, G., Bassi, A., Faccini, G.B., Bedogna, V., Gammaro, L., Brocco, G., Restivo, G., Bernich, P., Lupo, A. & Maschio, G. (2001) The role of iron status markers in predicting response to intravenous iron in haemodialysis patients on maintenance erythropoietin. Nephrology Dialysis Transplantation, 16, 1416-1423.
67. Tessitore, N., Girelli, D., Campostrini, N., Bedogna, V., Pietro Solero, G., Castagna, A., Melilli, E., Mantovani, W., De Matteis, G., Olivieri, O., Poli, A. & Lupo, A. (2010) Hepcidin is not useful as a biomarker for iron needs in hemodialysis patients on maintenance erythropoiesis-stimulating agents. Nephrology Dialysis Transplantation, 25, 3996-4002.
68. Thomas, C. & Thomas, L. (2002) Biochemical markers and hematologic indices in the diagnosis of functional iron deficiency. Clinical Chemistry, 48, 1066-1076.
69. Thomas, L., Franck, S., Messinger, M., Linssen, J., Thome, M. & Thomas, C. (2005) Reticulocyte hemoglobin measurement - comparison of two methods in the diagnosis of iron-restricted erythropoiesis. Clinical Chemistry Laboratory Medicine, 43, 1193-1202.
70. Thomas, C., Kirschbaum, A., Boehm, D. & Thomas, L. (2006) The diagnostic plot. A concept for identifying different states of iron deficiency and monitoring the response to epoietin therapy. Medical Oncology, 23, 23-36.
71. Thorpe, S.J., Heath, A., Sharp, G., Cook, J., Ellis, R. & Worwood, M. (2010) A WHO reference reagent for the Serum Transferrin Receptor (sTfR): international collaborative study to evaluate a recombinant transferrin receptor preparation. Clinical Chemistry Laboratory Medicine, 48, 815-820.
72. Urrechaga, E. (2009) Clinical utility of the new Beckman-Coulter parameter red blood cell size factor in the study of erythropoiesis. International Journal of Laboratory Haematology, 31, 623-629.
73. Urrechaga, E. (2010) The new mature red cell parameter, low haemoglobin density, of the Beckman Coulter LH750: clinical utility in the diagnosis of iron deficiency. International Journal of Laboratory Haematology, 32, 144-150.
74. Urrechaga, E., Borque, L. & Escanero, J.F. (2009) Potential utility of the new Sysmex XE 500 red blood cell extended parameters in the study of disorders of iron metabolism. Clinical Chemistry Laboratory Medicine, 47, 1411-1416.
75. Worwood, M. (1997) The laboratory assessment of iron status - an update. Clinica Chimica Acta, 259, 3-23.
76. van Wyck, D.B., Danielson, B.G. & Aronoff, G.R. (2004) Making sense: a scientific approach to intravenous iron therapy. Journal of The American Society of Nephrology, 15 (Suppl. 2), S91-S92.