Latent iron deficiency explained

Latent Iron Deficiency
Synonyms:	Iron-deficient erythropoiesis

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
• total iron binding capacity
• serum ferritin
• bone marrow examination (rarely)

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

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 will be normal for LID.

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

Serum ferritin levels reflect the iron stores available in the body. The normal range is 20 to 200 ng/mL for men and 15 to 150 ng/mL for women.^[8] Low levels (< 12 ng/mL) are specific for iron deficiency. However, inflammatory and neoplastic disorders can cause ferritin levels to increase – this may be seen in cases of hepatitis, leukemia, Hodgkin lymphoma, and GI tract tumors.

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.

Interpretation of diagnostic test results in terms of stage of iron deficiency

LID is present in stage 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.

Stage 1 is characterized by loss of bone marrow iron stores 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 consequent increased iron-binding capacity.

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

In stage 3, anemia (reduced hemoglobin levels) is present but red blood cell appearance remains normal.

Changes in the appearance of red blood cells are the hallmark of stage 4; first microcytosis and then hypochromia develop.

Iron deficiency begins to affect tissues in stage 5, manifesting as symptoms and signs.

Treatment

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

Epidemiology

Many studies have been done on 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 one year old (China):

Frequency of LID in different countries and populations:

• Poland: 14 of LID (11%) in 131 male athletes and 31 of ID (26%) in 121 female athletes^[15]
• India: 27.5% of LID amongst student nurses^[16]
• Spain: 14.7% of LID in 211 women of child-bearing age in Barcelona^[17]
• China: In 3591 pregnant and 3721 premenopausal women from 15 provinces. It was found: LID 42.6% in pregnant women (urban first-trimester 41.9%) (rural 36.1%) while 34.4% of LID in premenopausal non-pregnant women (urban 35.6%)(rural 32.4%).^[18] Pediatric samples: In 9118 children from 31 provinces aged 7 months to 7 years, the global incidence of LID in children was 32.5%. Sub-classifying the cases according to age and origin (global/countryside): less than 1 y (7m to 12m) LID 44.7% (35.8% in countryside), 1 – 3 years LID 35.9% (31% in countryside), 4 to 7 years (LID 26.5%) (30.1% in countryside).^[19]

Notes and References

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