Latent iron deficiency

Latent Iron Deficiency
Other names	Iron-deficient erythropoiesis
Specialty	Endocrinology

Latent iron deficiency (LID), also called iron-deficient erythropoiesis, ^[1] is a medical condition in which there is evidence of iron deficiency without anemia (normal hemoglobin level). ^[2] It is important to assess this condition because individuals with latent iron deficiency may develop iron-deficiency anemia. Additionally, there is some evidence of a decrease in vitality and an increase in fatigue among individuals with LID. ^[3]

Diagnosis

Diagnostic tests for latent iron deficiency (LID)

• complete blood count ^[4]
• hemoglobin ^[5]
• serum iron ^[4]
• total iron binding capacity ^[4]
• serum ferritin ^[4]
• bone marrow examination (rarely) ^[4]

Note: Iron therapy must be suspended 48 hours beforehand to ensure valid test results. ^[4]

The normal range for hemoglobin is 13.8 to 17.2 grams per deciliter (g/dL) for men and 12.1 to 15.1 g/dL for women. ^[6] Low hemoglobin indicates anemia but the individual will be normal for LID. ^[5]

Normal serum iron is between 60 and 170 micrograms per dL (μg/dL). ^[7] Normal total iron-binding capacity for both sexes is 240 to 450 μg/dL. ^[6] Total iron-binding capacity increases when iron deficiency exists. ^[4]

Serum ferritin levels reflect the body's available iron stores. ^[4] The normal range is 20 to 200 nanograms per milliliter (ng/mL) for men and 50 to 150 ng/mL for women. ^[8] Low levels (< 12 ng/mL) are specific for iron deficiency. ^[4] However, inflammatory and neoplastic disorders can cause ferritin levels to increase – this may be seen in cases of hepatitis, leukemia, Hodgkin lymphoma, and gastrointestinal (GI) tract tumors. ^[4]

The most sensitive and specific criterion for iron-deficient erythropoiesis is depleted iron stores in the bone marrow. However, in practice, a bone marrow examination is rarely needed. ^[4]

Interpretation of diagnostic test results

LID is present in Stages 1 and 2, before anemia occurs in Stage 3. These first two stages can be interpreted as depletion of iron stores and reduction of effective iron transport. ^[4]

Stage 1 – Characterized by loss of iron stores in the bone marrow while hemoglobin and serum iron levels remain normal. Serum ferritin falls to less than 20 ng/mL. Increased iron absorption, a compensatory change, results in an increased amount of transferrin and consequently increased iron-binding capacity. ^[4]

Stage 2 – Erythropoiesis is impaired. Despite an increased level of transferrin, the serum iron level is decreased, along with the transferrin saturation. Erythropoiesis impairment begins when the serum iron level falls to less than 50 μg/dL and transferrin saturation is less than 16%. ^[4]

Stage 3 – Anemia (reduced hemoglobin levels) is present, but red blood cell appearance remains normal. ^[4]

Stage 4 – Changes in the appearance of red blood cells are the hallmark of this stage; first microcytosis and then hypochromia develop. ^[4]

Stage 5 – Iron deficiency begins to affect tissues, manifesting as symptoms and signs. ^[4]

Treatment

There is no consensus on how to treat LID but one option is to treat it as iron-deficiency anemia by giving the individual ferrous sulfate (Iron(II) sulfate) at a dose of 100 mg per day in two doses (one at breakfast and the other at dinner) ^{[9] [10]} or 3 mg per kilogram (kg) per day in children (also in two doses) ^[11] for 2 or 3 months. The ideal is to increase the body's iron deposits, measured as levels of ferritin in serum, to reach a ferritin value between 30 and 100 ng/mL. A clinical study has shown an increase in ferritin levels in those taking iron compared with those taking a placebo. ^[12] With ferritin levels higher than 100 ng/mL, an increase in infections has been reported. ^[13] Another way to treat LID is with an iron-rich diet with ascorbic acid or vitamin C, contained in many types of fruits such as oranges, kiwifruits, etc., which will increase iron absorption 2- to 5-fold. ^{[14] [15]}

Epidemiology

Many studies have evaluated LID; its frequency varies according to country of origin, diet, pregnancy status, age, gender, etc. Depending on these previous conditions, the frequency can vary from 11% in male athletes (Poland) to 44.7% in children less than 1 year old (China):

The frequency of LID in different countries and populations is as follows:

• Poland: 14 of 131 male athletes (11%); 31 of 121 female athletes (26%) with ID ^[16]
• India: 27.5% amongst student nurses ^[17]
• Spain: 31 of 211 women of child-bearing age (14.7%) in Barcelona ^[18]
• China: In 3,591 pregnant and 3,721 premenopausal women from 15 provinces, LID was found in 1,529 (42.6%) pregnant women (urban first-trimester = 41.9%; rural = 36.1%) and in 1,280 (34.4%) premenopausal non-pregnant women (urban = 35.6%; rural = 32.4%). ^[19] For pediatric samples: in 9,118 children from 31 provinces, aged 7 months to 7 years old, the incidence of LID was 32.5% (2,963 children). Sub-classifying the cases according to age and origin (global/countryside): less than 1 year old (7 to 12 months), LID was 44.7% (35.8% in countryside); 1 – 3 years old, LID was 35.9% (31% in countryside); 4 to 7 years old, LID was 26.5% (30.1% in countryside). ^[20]

References

1. Suominen, P; Punnonen, K; Rajamäki, A; Irjala, K (October 1998). "Serum transferrin receptor and transferrin receptor-ferritin index identify healthy subjects with subclinical iron deficits" . Blood. 92 (8): 2934–9. doi:10.1182/blood.V92.8.2934. PMID   9763580.
2. Yehuda, Shlomo; Mostofsky, David I. (2010-03-10). Iron Deficiency and Overload: From Basic Biology to Clinical Medicine. Springer Science & Business Media. p. 302. ISBN   9781597454629.
3. Patterson, A. J.; Brown, W. J.; Roberts, D. C. (August 2001). "Dietary and supplement treatment of iron deficiency results in improvements in general health and fatigue in Australian women of childbearing age". Journal of the American College of Nutrition. 20 (4): 337–42. doi:10.1080/07315724.2001.10719054. PMID   11506061. S2CID   1886582.
4. "Iron Deficiency Anemia". Merck Manuals Professional Edition. Retrieved 2016-06-22.
5. "Iron deficiency anemia - Mayo Clinic". www.mayoclinic.org. Retrieved 2016-06-22.
6. "Hemoglobin: MedlinePlus Medical Encyclopedia". www.nlm.nih.gov. Retrieved 2016-06-22.
7. "Serum iron test: MedlinePlus Medical Encyclopedia". www.nlm.nih.gov. Retrieved 2016-06-22.
8. "Ferritin blood test: MedlinePlus Medical Encyclopedia". www.nlm.nih.gov. Retrieved 2016-06-22.
9. Norrby, A (1974). "Iron absorption studies in iron deficiency". Scandinavian Journal of Haematology. Supplementum. 20: 1–125. PMID   4526330.
10. Dallman, P. R. (1981). "Iron Deficiency: Diagnosis and Treatment". The Western Journal of Medicine. 134 (6): 496–505. PMC   1272837 . PMID   7257364.
11. Dallman, P. R.; Siimes, M. A.; Stekel, A (January 1980). "Iron deficiency in infancy and childhood". The American Journal of Clinical Nutrition. 33 (1): 86–118. doi: 10.1093/ajcn/33.1.86 . PMID   6986756.
12. Leonard, A. J.; Chalmers, K. A.; Collins, C. E.; Patterson, A. J. (April 2014). "Comparison of two doses of elemental iron in the treatment of latent iron deficiency: efficacy, side effects and blinding capabilities". Nutrients. 6 (4): 1394–405. doi: 10.3390/nu6041394 . PMC   4011041 . PMID   24714351.
13. Weiss, G; Goodnough, L. T. (March 2005). "Anemia of chronic disease". The New England Journal of Medicine. 352 (10): 1011–23. doi:10.1056/NEJMra041809. PMID   15758012.
14. Sayers, M. H.; Lynch, S. R.; Charlton, R. W.; Bothwell, T. H.; Walker, R. B.; Mayet, F (May 1974). "Iron absorption from rice meals cooked with fortified salt containing ferrous sulphate and ascorbic acid". The British Journal of Nutrition. 31 (3): 367–75. doi: 10.1079/BJN19740045 . PMID   4835790.
15. Sayers, M. H.; Lynch, S. R.; Charlton, R. W.; Bothwell, T. H.; Walker, R. B.; Mayet, P (December 1974). "The fortification of common salt with ascorbic acid and iron". British Journal of Haematology. 28 (4): 483–95. doi:10.1111/j.1365-2141.1974.tb06667.x. PMID   4455301. S2CID   5516683.
16. Malczewska, J; Szczepańska, B; Stupnicki, R; Sendecki, W (March 2001). "The assessment of frequency of iron deficiency in athletes from the transferrin receptor-ferritin index". International Journal of Sport Nutrition and Exercise Metabolism. 11 (1): 42–52. doi:10.1123/ijsnem.11.1.42. PMID   11255135.
17. Mehta, B. C. (September 2004). "Iron deficiency amongst nursing students". Indian Journal of Medical Sciences. 58 (9): 389–93. PMID   15470280.
18. Capel-Casbas, Maria J.; Duran, Jose J.; Diaz, Jorge; Ruiz, Gerardo; Simon, Ramon; Rodriguez, Francisco; Piqueras, Josep; Pelegri, Dolors; Pujol-Moix, Nuria (2005). "Latent Iron Metabolism Disturbances in Fertile Women and Its Detection with the Automated Hematology Instrument LH750®" . Blood. 106 (11): 3707. doi:10.1182/blood.V106.11.3707.3707.
19. Liao, Q. K.; Chinese Children, Pregnant Women & Premenopausal Women Iron Deficiency Epidemiological Survey Group (November 2004). "[Prevalence of iron deficiency in pregnant and premenopausal women in China: a nationwide epidemiological survey]". Zhonghua Xue Ye Xue Za Zhi (in Chinese). 25 (11): 653–7. PMID   15634568.
20. Zhu, Y. P.; Liao, Q. K.; Collaborative Study Group for "The Epidemiological Survey of Iron Deficiency in Children in China" (December 2004). "[Prevalence of iron deficiency in children aged 7 months to 7 years in China]". Zhonghua Er Ke Za Zhi (in Chinese). 42 (12): 886–91. PMID   15733354.