What is iron deficiency anemia?

Iron Deficiency Anemia: Definition, Diagnosis, and Management

Iron deficiency anemia (IDA) is the most severe form of iron deficiency, characterized by a shortage of iron that leads to underproduction of hemoglobin, resulting in microcytic and hypochromic red blood cells that impair oxygen transport to tissues. 1

Pathophysiology and Progression

Iron deficiency represents a spectrum that progresses through three stages:

1. Iron Depletion:

   • Reduced iron stores (low serum ferritin)
   • No physiological impairments
   • No iron stores available for mobilization when needed

2. Iron-Deficient Erythropoiesis:

   • Depleted iron stores
   • Reduced transport iron (low transferrin saturation)
   • Insufficient iron absorption to replace losses
   • Limited red blood cell production
   • Increased erythrocyte protoporphyrin concentration

3. Iron-Deficiency Anemia:

   • Most severe form of iron deficiency
   • Underproduction of iron-containing functional compounds, especially hemoglobin
   • Microcytic, hypochromic red blood cells 1

Epidemiology

• Affects approximately 2 billion people worldwide 2
• One of the most common nutritional deficiencies globally 1
• Particularly affects:
  • Women of reproductive age (38% have iron deficiency without anemia, 13% have IDA) 2
  • Pregnant women (up to 84% during third trimester) 2
  • Children (20.1% in industrialized countries between 0-4 years) 3
  • Elderly individuals 3
  • Patients with chronic inflammatory conditions 2

Common Causes

• Blood Loss:

  • Menstrual bleeding in women
  • Gastrointestinal bleeding (peptic ulcer disease, inflammatory bowel disease, bowel cancer)
  • Hookworm infections 1

• Decreased Absorption:

  • Atrophic gastritis
  • Celiac disease
  • Post-bariatric surgery 2

• Increased Requirements:

  • Pregnancy
  • Rapid growth in children
  • Chronic inflammatory conditions 1, 2

• Inadequate Dietary Intake 2

Clinical Manifestations

• Fatigue and weakness
• Developmental delays and behavioral disturbances in children
• Impaired work capacity in adults
• Increased risk for preterm delivery and low-birthweight babies in pregnant women
• Dyspnea and exercise intolerance
• Irritability, depression, difficulty concentrating
• Restless legs syndrome (32-40%)
• Pica (40-50%)
• Worsening heart failure in affected patients 1, 2

Diagnosis

Laboratory Tests

• Hemoglobin and Hematocrit:

  • Most common screening tests
  • Late indicators of iron deficiency
  • Low specificity and sensitivity when used alone 1

• Serum Ferritin:

  • Confirms iron deficiency (typically <30 ng/mL)
  • May be falsely elevated in inflammatory conditions 2

• Transferrin Saturation:

  • Less than 20% indicates iron deficiency
  • Useful in inflammatory conditions when ferritin may be unreliable 2

• Additional Tests when needed:

  • Erythrocyte zinc protoporphyrin concentration
  • Serum iron concentration 4

Diagnostic Criteria

• Anemia: Hemoglobin below 5th percentile for age, sex, and pregnancy status
• Iron deficiency: Low serum ferritin or low transferrin saturation
• IDA: Anemia plus evidence of iron deficiency 1

Management

Oral Iron Therapy

• First-line treatment for most patients 5, 2

• Dosing:

  • Adults: 200 mg elemental iron daily in 2-3 divided doses
  • Alternative: Single daily dose of ferrous sulfate 200 mg (65 mg elemental iron)
  • Children: 2-3 mg/kg/day of elemental iron 5

• Formulations:

  • Ferrous sulfate (preferred): 65 mg elemental iron per 325 mg tablet
  • Ferrous fumarate: 108 mg elemental iron per 325 mg tablet
  • Ferrous gluconate: 35 mg elemental iron per 325 mg tablet 5

• Administration:

  • Take on empty stomach (2 hours before or 1 hour after meals)
  • Add vitamin C (250-500 mg) to enhance absorption
  • Avoid taking with calcium or phosphate binders 5

Intravenous Iron Therapy

• Indications:

  • Oral iron intolerance
  • Poor absorption (celiac disease, post-bariatric surgery)
  • Chronic inflammatory conditions (CKD, heart failure, IBD, cancer)
  • Ongoing blood loss
  • Second and third trimesters of pregnancy when needed
  • Hemoglobin below 10 g/dL requiring rapid correction 5, 2

• Dosing based on weight and hemoglobin level 5

Duration of Treatment

• Continue for 3 months after hemoglobin normalization to replenish iron stores 5

Monitoring

• Check hemoglobin after 2-4 weeks of treatment (expect ~2 g/dL increase)
• Monitor hemoglobin and red cell indices every 3 months for 1 year, then after another year
• Target values:
  • Hemoglobin >12 g/dL for women, >13 g/dL for men
  • Ferritin >100 μg/L
  • Transferrin saturation >20% 5

Special Considerations

Children

• Iron deficiency in infants and preschool children can cause developmental delays and behavioral disturbances
• These delays may persist past school age if not fully reversed
• Iron deficiency also increases lead absorption in children 1

Pregnant Women

• Iron deficiency during first two trimesters increases risk for preterm delivery and low-birthweight babies
• Iron supplementation decreases incidence of IDA during pregnancy 1

Chronic Conditions

• Patients with chronic kidney disease, heart failure, inflammatory bowel disease, and cancer often require intravenous iron therapy 5, 2

Common Pitfalls to Avoid

• Stopping treatment too early before iron stores are replenished
• Using divided doses when a single daily dose may be better tolerated
• Failing to add vitamin C to enhance absorption
• Administering oral iron with absorption inhibitors
• Using parenteral iron when oral therapy would be effective
• Inadequate dosing that underestimates total iron deficit
• Delaying iron treatment until the underlying condition resolves
• Failure to investigate underlying causes, especially in men and postmenopausal women 5

Importance of Identifying Underlying Cause

• In men and postmenopausal women, investigate for sources of blood loss, especially gastrointestinal
• About one-third of adults over 50 with IDA have an underlying bleeding abnormality, and about one-third of these have cancer 1
• Endoscopy or CT scanning is recommended for unexplained IDA in this age group, even without other relevant symptoms 1