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Iron deficiency anemia

Last updated: July 23, 2021

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Iron deficiency anemia (IDA) is the most common form of anemia worldwide and can be caused by inadequate intake, decreased absorption (e.g., atrophic gastritis, inflammatory bowel disease), increased demand (e.g., during pregnancy), or increased loss (e.g., gastrointestinal bleeding, menorrhagia) of iron. Prolonged deficiency depletes iron stores in the body, resulting in decreased erythropoiesis and anemia. Symptoms are nonspecific and include fatigue, pallor, lethargy, hair loss, brittle nails, and pica. While IDA typically manifests as a hypochromic and microcytic anemia, it may also be normocytic. A low ferritin level is diagnostic for iron deficiency, but further iron studies may be necessary, especially in patients with chronic inflammation. Once IDA is diagnosed, the underlying cause must be determined. This typically involves a gastroscopy and colonoscopy or a gynecologic workup in women with abnormal uterine bleeding. Iron deficiency anemia is treated with oral or parenteral iron supplementation. Patients with anemia severe enough to cause cardiopulmonary instability require blood transfusions.

See also “Anemia.”

  • Most common form of anemia worldwide [1]
  • ∼ 3% of the general population in the United States is affected. [2]
  • African-American and Mexican-American populations in the US are at increased risk.
  • Prevalence highest in: [3]
    • Children up to 5 years of age
    • Young women of child-bearing age (due to menstrual blood loss)
    • Pregnant women

Epidemiological data refers to the US, unless otherwise specified.

The most common causes of IDA can be divided by age group and pathophysiologic mechanism.

Based on age [1][4]

In resource-limited countries, adults > 50 years that present with IDA should have colon polyps/carcinoma ruled out as a potential underlying etiology.

Based on underlying mechanism [4][6][7]

DICEd Plumm - Dysphagia, Iron deficiency anemia, Carcinoma of the esophagus, Esophageal webs in Plummer-Vinson syndrome.

References:[2][11]

Approach

  • Initial investigations
  • Empiric iron therapy can be initiated if:
    • The patient's history points to a clear explanation for IDA (e.g., history of multiple blood donations or inadequate nutritional iron intake)
    • No pathology is found in a young, otherwise healthy patient after the initial investigations
  • Advanced studies (e.g., capsule endoscopy, angiographic or scintigraphic studies): Consider in older symptomatic patients with negative initial workup and no response to empiric iron therapy. [12]

Routine studies [1][12][13]

Diagnosis of iron deficiency [1][4][13][18]

In combination with an elevated TIBC, low ferritin and iron levels are diagnostic of iron deficiency anemia.

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

Evaluation for underlying cause [1][18]

Evaluation for underlying causes of iron deficiency [12][18]
Suspected etiology Indications Studies
Gastrointestinal pathologies
  • Origin from or recent travel to resource-limited subtropical or tropical area
  • Eosinophilia on CBC
Gynecological pathologies
Renal pathologies
Pulmonary pathologies
  • Iron-staining of sputum sample
  • Chest imaging as appropriate

Treatment of the underlying condition

Examples include:

Dietary modifications

  • All patients
    • Encourage consumption of iron-rich foods.
    • Counsel patients taking iron supplements to avoid the following substances that reduce iron absorption: [1][13]
  • Infants < 1 year old: Avoid cow's milk. [12]

Iron therapy

Oral supplementation is effective and inexpensive, however, adherence is often poor due to side effects. Parenteral iron therapy is beneficial in select cases.

Iron therapy for iron deficiency anemia
Oral iron therapy Parenteral iron therapy [1][13]
Indications
  • Indicated in all patients with IDA (if tolerated)
Agents
  • Ferrous sulfate
  • Ferrous fumarate
  • Ferrous gluconate
  • Ferric preparations
  • Others: ferrous gluconate, ferumoxytol
Dosage [13]
  • Adults: typically the equivalent of 100–200 mg elemental iron daily [13][18]
  • Children: 3–6 mg/kg per day in a liquid preparation [1][4]
  • Available forms (ferrous preparations)
    • Ferrous sulfate [13]
    • Ferrous fumarate [13]
    • Ferrous gluconate [13]
  • Absorption may be enhanced by simultaneous consumption of vitamin C (e.g., in orange juice).
  • Determine iron deficit using the Ganzoni formula. [13]
  • Choose a replacement preparation.
  • Administer in one or several sittings until calculated iron deficit is replaced. [13]
  • Iron dextran
  • Iron sucrose
  • Ferrous gluconate
  • Ferumoxytol
Adverse effects [1][22]
  • Gastrointestinal discomfort, nausea, constipation, black discoloration of stool
Duration
  • Should initially be administered for 3–6 months or three months after correction of anemia in order to build iron stores [1][4]
  • Depends on the iron deficit and chosen IV preparation
Monitoring [1]
  • Check CBC monthly until in normal range, then every three months for one year, then once again after another year.
  • Adequate response: After one month, hemoglobin should have increased by ≥ 1 g/dL.

Blood transfusion [23][24]

See “Transfusion” for further information.

  • Consider pRBCs in:
    • Hemodynamically unstable patients with anemia
    • Severe anemia (Hb ≤ 7 g/dL)
    • Select patients with Hb ≤ 8 g/dL
  • Avoid pRBCs in: hemodynamically stable patients with mild or moderate IDA.

See "Diagnostics" in “Anemia.”

Iron deficiency anemia Anemia of chronic disease
Ferritin Normal to
Iron normal to ↓
Transferrin/TIBC Slightly ↓
Transferrin saturation Normal to slightly ↓
RDW normal
Soluble transferrin receptor (sTfR) normal

References:[2][25]

The differential diagnoses listed here are not exhaustive.

Screening [26][27][28]

  • Universal screening is generally not recommended in adults
  • The American Academy of Pediatrics (AAP) recommends one-time laboratory screening (Hb level) in all infants at the age of 9–12 months
  • All infants and children between 4–36 months should be clinically assessed for risk factors of iron deficiency at every well child examination, followed by annual assessments thereafter.
  • Selective screening (Hb level) in individuals who are at increased risk of iron deficiency

Recommendations for breastfed infants [26]

  • Preterm breastfed infants should receive 2mg/kg per day supplemental iron for the first 12 months of life.
  • Term breastfed children > 6 months should receive dietary iron (e.g., fortified cereal) or oral iron 1mg/kg per day.

Iron deficiency anemia in pregnancy

  • Epidemiology
    • > 40% of pregnant women are iron deficient [29]
    • Second most common cause of anemia in pregnant women (after physiologic anemia)
  • Etiology: increased iron requirements
  • Treatment: oral or IV iron supplementation (see “Treatment” above) [30][31]
  • Complications
    • Increased risk of adverse pregnancy outcomes
    • Impaired fetal neurodevelopment
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