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Vol. 39. Núm. 3.Julho - Setembro 2017
Páginas 187-292
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Vol. 39. Núm. 3.Julho - Setembro 2017
Páginas 187-292
Scientific Comment
DOI: 10.1016/j.bjhh.2017.03.005
Challenges in the diagnosis of iron deficiency anemia in aged people
Niele Silva de Moraesa,b, Maria Stella Figueiredoa,
Autor para correspondência

Corresponding author at: Disciplina de Hematologia e Hemoterapia, Escola Paulista de Medicina da Universidade Federal de São Paulo (EPM/UNIFESP), R Dr. Diogo de Farias, 824, 04037-002 Vila Clementino, São Paulo, SP, Brazil.
a Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil
b Universidade do Estado do Pará (UEPA), Belém, PA, Brazil
Conteúdo relacionado
Rev Bras Hematol Hemoter 2017;39:223-810.1016/j.bjhh.2017.02.002
Mansour Babaei, Sajedeh Shafiei, Ali Bijani, Behzad Heidari, Seyed Reza Hosseyni, Mohsen Vakili Sadeghi
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In this issue of the Brazilian Journal of Hematology and Hemotherapy, Babaei et al.1 investigated the cut-off level for serum ferritin that would better discriminate between elderly patients with and without iron deficiency anemia (IDA).

IDA is a common manifestation among the elderly population. It has often been associated to gastrointestinal bleeding caused by esophagitis, gastritis, peptic ulcer, cancer, and intestinal polyps.2–5Although a bone marrow examination is the gold standard test to assess iron stores, it is an invasive method with no practical applicability.6,7 A recent systematic review showed that all guidelines recommend the measurement of serum ferritin to diagnose IDA.8 Serum ferritin is considered a first-line diagnostic tool not only due to its availability, but also because its plasmatic levels accurately reflect overall iron storage, with 1ng of ferritin per mL indicating approximately 10mg of total iron stores.1,9

While serum ferritin under 10–15ng/mL has 99% of specificity in the diagnosis of IDA, normal or elevated ferritin levels do not exclude IDA, since ferritin is an acute phase protein and may increase during inflammation, cancer, and with aging.8,10 Hence, some studies provide data supporting the use of higher ferritin thresholds for diagnosis, such as 30 or 100ng/mL.11,12

Elderly people often have many morbidities some of which can potentially lead to anemia, making the diagnosis of IDA particularly challenging in this population.13 Moreover, in individuals with chronic diseases, anemia of inflammation (AI) can be associated with an absolute iron deficiency, especially in cases where there is bleeding.14

It is recommended to expand the repertoire of biochemical markers to differentiate between AI and AI with iron deficiency (AI+IDA). These markers include red cell variables (such as hypochromic red cells and reticulocyte-specific indices of volume and hemoglobin content), transferrin saturation, soluble transferrin receptor (sTfR), and hepcidin.13–17

Among the red cell variables, hypochromic red cells are used to identify absolute iron deficiency in patients with chronic renal failure, whereas reticulocyte-specific indices are used to assess the iron status of these cells.8 However, the difficulties in the diagnosis of AI+IDA using these parameters remain.14

Transferrin saturation is cheap and available in most laboratories, and is quite suggestive of IDA when below 16%. However, inflammatory illnesses affect transferrin saturation and conclusions may be misleading if used as the sole marker.8,10,16

sTfR is an indicator of iron status and is elevated in IDA. It can be useful in the diagnosis of AI+IDA although it is relatively expensive and not widely available.3,10,18 The TfR index, a ratio between sTfR and log of ferritin, is considered a good indicator of IDA in patients with chronic diseases, but it depends on the viability of the sTfR measurement.7,18

Hepcidin, a 25 amino-acid peptide discovered at the beginning of this century, is a regulator of iron metabolism. This molecule induces the degradation of ferroportin, a membrane protein responsible for iron transport.19,20 Low levels of hepcidin are seen in IDA anemia, while the opposite is true in AI. However, this test is most often used in research institutions.19–21

The diagnosis of IDA is not always simple. Serum ferritin alone is no longer recommended as the only diagnostic test to assess IDA in the elderly.8,13 Furthermore, the other laboratorial exams have low sensitivity or are not widely available.21 The challenge remains and any studies that identify parameters of value during clinical decision-making are welcome.

Conflicts of interest

The authors declare no conflicts of interest.


This work was supported by research grant from FAPESP (13/12161-9).

M. Babaei,S. Shafiee,A. Bijani,B. Heidari,R.S. Hosseini,M.V. Sadeghi
Ability of serum ferritin for diagnosis of iron deficiency anemia in an elderly cohort
Rev Bras Hematol Hemoter, 39 (2017), pp. 223-228
T.G. DeLoughery
Iron deficiency anemia
Med Clin North Am, 101 (2017), pp. 319-332
E. Andres,K. Serraj,L. Federici,T. Vogel,G. Kaltenbach
Anemia in elderly patients: new insight into an old disorder
Geriatr Gerontol Int, 13 (2013), pp. 519-527
R. Stauder,S.L. Thein
Anemia in the elderly clinical implications and new therapeutic concepts
Haematologica, 99 (2014), pp. 1127-1130
L.T. Goodnough,S.L. Schrier
Evaluation and management of anemia in the elderly
Am J Hematol, 89 (2014), pp. 88-96
J. Bahrainwala,J.S. Berns
Diagnosis of iron-deficiency anemia in chronic kidney disease
D.W. Thomas,R.F. Hinchliffe,C. Briggs,I.C. Macdougall,T. Littlewood,I. Cavill
Guideline for the laboratory diagnosis of functional iron deficiency
Br J Haematol, 161 (2013), pp. 639-648
L. Peyrin-Biroulet,N. Williet,Cacoub P.
Guidelines on the diagnosis and treatment of iron deficiency across indications a systematic review
Am J Clin Nutr, 102 (2015), pp. 1585-1594
G.H. Guyatt,A.D. Oxman,M. Ali,A. Willan,W. McIlroy,C. Patterson
Laboratory diagnosis of iron-deficiency anemia an overview
J Gen Intern Med, 7 (1992), pp. 145-153
C.A. Finch,V. Bellotti,S. Stray,D.A. Lipschitz,J.D. Cook,M.J. Pippard
Plasma ferritin determination as a diagnostic tool
West J Med, 145 (1986), pp. 657-663
A.J. Friedman,A. Shander,S.R. Martin,R.K. Calabrese,M.E. Ashton,I. Lew
Iron deficiency anemia in women: a practical guide to detection, diagnosis, and treatment
Obstet Gynecol Surv, 70 (2015), pp. 342-353
A. Zhu,M. Kaneshiro,J.D. Kaunitz
Evaluation and treatment of iron deficiency anemia a gastroenterological perspective
Dig Dis Sci, 55 (2010), pp. 548-559
N.M. Archer,C. Brugnara
Diagnosis of iron-deficient states
Crit Rev Clin Lab Sci, 52 (2015), pp. 256-272
A.B. Torino,F. Gilberti Mde,E. Da Costa,G.A. De Lima,H.Z. Grotto
Evaluation of erythrocyte and reticulocyte parameters as indicative of iron deficiency in patients with anemia of chronic disease
Rev Bras Hematol Hemoter, 37 (2015), pp. 77-81
M. Basora Macaya,E. Bisbe Vives
The first pillar of patient blood management. Types of anemia and diagnostic parameters
Rev Esp Anestesiol Reanim, 62 (2015), pp. 19-26
F. Bermejo,S. Garcia-Lopez
A guide to diagnosis of iron deficiency and iron deficiency anemia in digestive diseases
World J Gastroenterol, 15 (2009), pp. 4638-4643
S. Killip,J.M. Bennett,M.D. Chambers
Iron deficiency anemia
Am Fam Physician, 75 (2007), pp. 671-678
D.H. Shin,H.S. Kim,M.J. Park,I.B. Suh,K.S. Shin
Utility of access soluble transferrin receptor (sTfR) and sTfR/log ferritin index in diagnosing iron deficiency anemia
Ann Clin Lab Sci, 45 (2015), pp. 396-402
T. Ganz
Hepcidin a key regulator of iron metabolism and mediator of anemia of inflammation
L. Ferrucci,R.D. Semba,J.M. Guralnik,W.B. Ershler,S. Bandinelli,K.V. Patel
Proinflammatory state hepcidin and anemia in older persons
F. Busti,N. Campostrini,N. Martinelli,D. Girelli
Iron deficiency in the elderly population revisited in the hepcidin era
Front Pharmacol, 5 (2014), pp. 83

See paper by Flávio Augusto Naoum et al. on pages 223–8.

Copyright © 2017. Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular
Revista Brasileira de Hematologia e Hemoterapia

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