How is iron deficiency diagnosed and treated?

Diagnosis and Treatment of Iron Deficiency

Iron deficiency is diagnosed primarily through serum ferritin measurement, with a cutoff of <45 ng/mL being diagnostic, while treatment should begin with oral iron supplementation (ferrous sulfate 65mg elemental iron daily) for most patients and intravenous iron for those with specific indications. 1

Diagnostic Approach

Laboratory Testing

• Serum ferritin is the most powerful diagnostic test for iron deficiency 1:

  • <30 μg/L: Definitive iron deficiency 2
  • 30-100 μg/L with transferrin saturation <20%: Possible iron deficiency, especially with inflammation 2

  • 100 μg/L: Iron deficiency almost certainly not present 1

• In patients with inflammation, chronic disease, or malignancy:

  • Ferritin cutoff should be raised to <100 μg/L 1
  • Transferrin saturation <16% supports diagnosis of iron deficiency 1
  • Ferritin between 30-100 μg/L with low transferrin saturation suggests combined iron deficiency and anemia of chronic disease 1

• Additional tests when diagnosis remains unclear:

  • Serum transferrin receptor (elevated in iron deficiency) 3
  • Therapeutic response to iron (increase in hemoglobin ≥1 g/dL after 4 weeks confirms diagnosis) 1
  • Red cell distribution width (RDW) - elevated in iron deficiency 1

Evaluation for Underlying Causes

Gastrointestinal evaluation should be considered in all patients with confirmed iron deficiency unless there is a history of significant non-GI blood loss 1:

• Upper GI endoscopy with small bowel biopsies (2-3% of patients with iron deficiency anemia have celiac disease) 1
• Lower GI evaluation (colonoscopy) should be performed in all patients unless upper GI endoscopy reveals carcinoma or celiac disease 1
• Testing for H. pylori should be considered in patients with iron deficiency anemia 1

Treatment Algorithm

First-line Treatment

• Oral iron supplementation:
  • Ferrous sulfate 65mg elemental iron daily (standard dosing) 2
  • Administer between meals to maximize absorption 1
  • Continue for 3 months after normalization of hemoglobin to replenish iron stores 2

Monitoring Response

• Check hemoglobin within 4 weeks of starting therapy 2
• Expected response: Increase in hemoglobin of ≥1 g/dL within 4 weeks 1, 2
• If no response despite compliance, further evaluation is needed 1

Intravenous Iron Indications

Consider IV iron as first-line in patients with:

• Intolerance to oral iron 2
• Conditions impairing iron absorption (celiac disease, post-bariatric surgery) 2, 4
• Active inflammatory bowel disease 2
• Chronic kidney disease requiring rapid iron repletion 5
• Heart failure with iron deficiency 1
• Ongoing blood loss 4
• Second and third trimesters of pregnancy when rapid repletion is needed 4

Special Populations

Patients with Heart Failure

• Screen all newly diagnosed heart failure patients for iron deficiency 1
• Diagnose iron deficiency when:
  • Ferritin <100 μg/L, or
  • Ferritin 100-299 μg/L with transferrin saturation <20% 1

Children and Infants

• Universal screening recommended for high-risk populations (low-income families, WIC-eligible) between 9-12 months, 6 months later, and annually from ages 2-5 years 1
• Selective screening for children with risk factors (preterm birth, non-iron-fortified formula, early cow's milk introduction) 1

Pregnant Women

• Iron deficiency affects up to 84% of pregnant women in the third trimester 4
• Intravenous iron may be indicated during second and third trimesters when rapid repletion is needed 4

Common Pitfalls to Avoid

• Failing to identify the underlying cause of iron deficiency, particularly in men and postmenopausal women where gastrointestinal malignancy must be excluded 2, 4
• Using inappropriate ferritin cutoffs in patients with inflammation (should use <100 μg/L rather than <30 μg/L) 1
• Relying solely on hemoglobin for diagnosis (low sensitivity and specificity) 3
• Stopping iron supplementation too early before replenishing stores (should continue for 3 months after hemoglobin normalization) 2
• Mistaking infusion reactions for true anaphylaxis during IV iron administration 2
• Assuming dietary deficiency as the sole cause without appropriate investigation 1

By following this structured approach to diagnosis and treatment, iron deficiency can be effectively managed to improve patient outcomes, reduce morbidity, and enhance quality of life.