• Clinical science

Iron deficiency anemia

Abstract

Iron deficiency anemia (IDA) is the most common cause of anemia worldwide and can be due to inadequate intake, decreased absorption (e.g., atrophic gastritis, IBD), increased demand (e.g., during pregnancy), or increased loss (e.g., GI bleeding, menorrhagia). Prolonged deficiency depletes the iron stores in the body, resulting in decreased erythropoiesis and IDA. Symptoms are nonspecific and include fatigue, pallor, lethargy, hair loss, brittle nails, and pica. Some patients may also present with features of cardiac failure (e.g., dyspnea on exertion, pedal edema). Low hemoglobin, microcytic hypochromic blood picture on peripheral smear, and iron studies (ferritin and transferrin saturation, transferrin levels) are used to diagnose IDA. Once diagnosed, the etiology should be determined. Stool examination for hookworm ova and occult blood are indicated in all patients with IDA. Patients at high risk of underlying GI malignancy (men of all ages/postmenopausal women with IDA) should also undergo colonoscopy and endoscopy. Iron deficiency anemia is treated with oral (most common) or parenteral supplementation of iron. Severe anemia or those with concomitant cardiac conditions may also require blood transfusions. The underlying cause for IDA should also be corrected.

Epidemiology

  • Prevalence
    • Most common form of anemia (80%)
    • According to the WHO, more than two billion people worldwide are affected by iron deficiency.
    • ∼ 3% of the general population in the United States have IDA.
  • At-risk groups
    • Young women (due to menstrual blood loss)
    • Pregnant women
    • Extremes of age: infants and young children (esp. premature/low birth weight infants), age > 65 years
    • Racial variations: Black/Mexican population (genetic predisposition)

References:[1][2][3][4][5]

Epidemiological data refers to the US, unless otherwise specified.

Etiology

  • Decreased intake
    • Cereal-rich diet
    • Chronic undernutrition
  • Decreased absorption
    • Achlorhydria/hypochlorhydria (e.g., due to autoimmune or H. pylori infection induced atrophic gastritis)
    • Inflamed/ulcerated intestinal mucosa: Inflammatory bowel disease, Celiac disease
    • Bariatric surgery
    • In children: excessive intake of cow's milk (> 24 ounces/700 mL per day)
      • In addition to low iron content, the calcium and proteins in cow's milk disrupt iron absorption.
    • In infants: substituting breastfeeding and/or iron-fortified formulas with cow's milk
      • Also seen in exclusively breastfed infants older than 6 months of age without proper iron supplementation
  • Increased demand
  • Iron loss

References:[4][7][8][9]

Pathophysiology

References:[10][11][12]

Clinical features

References:[2][13][14][15][16]

Diagnostics

Laboratory tests

Other tests

Low ferritin and iron levels in combination with an elevated TIBC are diagnostic for iron deficiency anemia!

Increased ferritin does not rule out iron deficiency anemia. It can be increased in response to simultaneous inflammation!

References:[10][2][17][18]

Treatment

  • Dietary modifications
    • Infants and young children: restrict feeding with cow's milk and use iron-fortified formula, introduction of meats (pureed form)
    • Adults: increased consumption of iron-rich diet (meats, use of iron-fortified food, fresh green leafy vegetables)
  • Oral iron therapy: indicated in all patients with IDA (who can tolerate it)
    • Available forms (ferrous preparations): ferrous sulfate, ferrous fumarate, and ferrous gluconate
    • Adverse effects: gastrointestinal discomfort, black discoloration of stool
  • Parenteral iron therapy
  • Blood transfusion
    • Severe anemia (Hb < 7 g/dL)
    • Cardiac patients with Hb < 10 g/dL
    • Patients with features of cardiac failure (dyspnea on exertion, pedal edema)
  • Treat the underlying disease (e.g., antihelminthics for hookworm, NSAIDs and/or OCPs for menorrhagia)
  • Response to treatment: Clinical symptoms rapidly improve; Hb should rise by 1 g/dL every 2–3 weeks.
  • Monitoring: Check Hb and reticulocyte level 2 weeks after oral therapy or 4 weeks after parenteral therapy.

References:[19][2]

Differential diagnoses

Iron deficiency anemia Anemia of chronic disease
Ferritin = to ↑
Iron = to ↓
Transferrin/TIBC slightly ↓
Transferrin saturation = to slightly ↓
RDW =
TfR =

See "Diagnostics" in learning card on anemia for a table on differentiating features of types of microcytic anemia.

References:[2][17]

The differential diagnoses listed here are not exhaustive.

  • 1. Miller JL. Iron deficiency anemia: a common and curable disease. Cold Spring Harb Perspect Med. 2013; 3(7). doi: 10.1101/cshperspect.a011866.
  • 2. Killip S, Bennett JM, Chambers MD. Iron deficiency anemia. Am Fam Physician. 2007; 75(5): pp. 671–678. pmid: 17375513.
  • 3. National Institutes of Health. Who Is at Risk for Iron-Deficiency Anemia?. https://www.nhlbi.nih.gov/health/health-topics/topics/ida/atrisk. Updated March 26, 2014. Accessed February 28, 2017.
  • 4. Schrier SL. Causes and Diagnosis of Iron Deficiency and Iron Deficiency Anemia in Adults. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/causes-and-diagnosis-of-iron-deficiency-and-iron-deficiency-anemia-in-adults. Last updated January 10, 2017. Accessed February 28, 2017.
  • 5. Laura Percy, Diana Mansour. Iron deficiency and iron-deficiency anaemia in women's health. The Obstetrician & Gynaecologist. 2017; 19(2): pp. 155–161. doi: 10.1111/tog.12368.
  • 6. Sostres C, Gargallo CJ, Lanas A. Nonsteroidal anti-inflammatory drugs and upper and lower gastrointestinal mucosal damage. Arthritis Res Ther. 2013; 15(Suppl 3): p. S3. doi: 10.1186/ar4175.
  • 7. Institute of Medicine (US) Committee on Use of Dietary Reference Intakes in Nutrition Labeling. Dietary Reference Intakes, Guiding Principles for Nutrition Labeling and Fortification. Washington, D.C.: National Academies Press; 2003.
  • 8. Anderson GJ, McLaren GD. Iron Physiology and Pathophysiology in Humans. Springer Science & Business Media; 2012.
  • 9. Powers JM, Mahoney DH. Iron Deficiency in Infants and Children <12 Years: Screening, Prevention, Clinical Manifestations, and Diagnosis. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/iron-deficiency-in-infants-and-children-less-than12-years-screening-prevention-clinical-manifestations-and-diagnosis. Last updated December 14, 2017. Accessed April 4, 2018.
  • 10. Kumar V, Abbas AK, Aster JC. Robbins & Cotran Pathologic Basis of Disease. Philadelphia, PA: Elsevier Saunders; 2014.
  • 11. Soe-Lin S, Apte SS, Andriopoulos B Jr. Nramp1 promotes efficient macrophage recycling of iron following erythrophagocytosis in vivo. Proc Natl Acad Sci U S A. 2009; 106(14): pp. 5960–5965. doi: 10.1073/pnas.0900808106.
  • 12. University of Washington. Iron Absorption. https://courses.washington.edu/conj/bess/iron/iron.htm. Updated February 28, 2017. Accessed February 28, 2017.
  • 13. Novacek G. Plummer-Vinson syndrome. Orphanet J Rare Dis. 2006; 1(36). doi: 10.1186/1750-1172-1-36.
  • 14. OMICS International. Angular Cheilitis. http://research.omicsgroup.org/index.php/Angular_cheilitis. Updated February 28, 2017. Accessed February 28, 2017.
  • 15. Khan Y, Tisman G. Pica in iron deficiency: a case series. J Med Case Reports. 2010; 4: p. 86. doi: 10.1186/1752-1947-4-86.
  • 16. V. Bhagavan N. Medical Biochemistry. Elsevier; 2001.
  • 17. Bermejo F, García-López S. A guide to diagnosis of iron deficiency and iron deficiency anemia in digestive diseases. World J Gastroenterol. 2009; 15(37): pp. 4638–4643. pmid: 19787826.
  • 18. Wei K-Y, Yan Q, Tang B, et al. Hookworm infection: a neglected cause of overt obscure gastrointestinal bleeding. Korean J Parasitol. 2017; 55(4): pp. 391–398. doi: 10.3347/kjp.2017.55.4.391.
  • 19. Carson JL, Grossman BJ, Kleinman S et al. Red Blood Cell Transfusion: A Clinical Practice Guideline From the AABB. Ann Intern Med. 2012; 157(1): pp. 49–58. doi: 10.7326/0003-4819-157-1-201206190-00429.
  • Medical Pictures Info. Koilonychia. url: http://medicalpicturesinfo.com/wp-content/uploads/2011/11/Koilonychia-1.jpg Accessed February 28, 2017.
last updated 02/15/2019
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