What is the recommended workup and treatment for iron deficiency anemia?

Workup and Treatment of Iron Deficiency Anemia

The recommended workup for iron deficiency anemia includes diagnostic testing with ferritin (using a cutoff of 45 mg/dL) and transferrin saturation, followed by gastrointestinal evaluation with upper and lower endoscopy in patients over 45 years to identify the underlying cause, and treatment with oral iron supplementation at 200 mg ferrous sulfate three times daily for most patients. 1

Diagnostic Approach

Initial Laboratory Testing

• Ferritin is the most sensitive and specific test for diagnosing iron deficiency
  • Use cutoff of 45 mg/dL in patients with anemia 1
  • Note: In inflammatory conditions, ferritin may be falsely elevated (up to 100 mg/dL) despite iron deficiency
• Additional confirmatory testing when ferritin is borderline or elevated:
  • Transferrin saturation (<20% suggests iron deficiency)
  • Soluble transferrin receptor
  • Reticulocyte hemoglobin equivalent

Identifying the Underlying Cause

• For patients >45 years: Both upper GI endoscopy with small bowel biopsy AND lower GI evaluation (colonoscopy or barium enema) are recommended unless a firm cause is found with the first investigation 1
• For patients <45 years:
  • With upper GI symptoms: Endoscopy and small bowel biopsy
  • Without GI symptoms: Anti-endomysial antibody testing (with IgA levels) to exclude celiac disease
  • Colonic investigation only if specific indications present 1
• Special considerations:
  • Menstruating women: Evaluate menstrual blood loss (heavy menstrual bleeding is common cause)
  • Check for H. pylori infection which can impair iron absorption
  • Consider other causes of malabsorption (celiac disease, post-bariatric surgery)

Treatment Algorithm

First-Line Treatment: Oral Iron Therapy

• Standard regimen: Ferrous sulfate 200 mg three times daily (provides ~65 mg elemental iron per dose) 1
• Alternative oral preparations if intolerance occurs:
  • Ferrous gluconate or ferrous fumarate (equally effective)
  • Liquid preparations if tablets not tolerated
• Adjunctive therapy:
  • Add ascorbic acid (vitamin C) to enhance iron absorption if response is poor 1
• Expected response:
  • Hemoglobin should rise by 2 g/dL after 3-4 weeks 1
  • Continue treatment for 3 months after anemia correction to replenish iron stores 1

When to Consider Intravenous Iron

Intravenous iron is indicated in:

1. Patients with inflammatory bowel disease with active inflammation (compromised absorption) 1
2. Intolerance to at least two oral iron preparations 1
3. Documented non-compliance with oral therapy
4. Ongoing blood loss where oral therapy cannot keep pace
5. Portal hypertensive gastropathy with ongoing bleeding unresponsive to oral iron 1

Follow-up Monitoring

• Monitor hemoglobin and red cell indices at 3-month intervals for one year, then after another year 1
• Provide additional oral iron if hemoglobin or MCV falls below normal
• Further investigation is warranted if anemia cannot be maintained with supplementation

Special Clinical Scenarios

Inflammatory Bowel Disease

• Determine if anemia is due to inadequate intake/absorption or blood loss
• Treat active inflammation to enhance iron absorption
• Use IV iron therapy when active inflammation compromises absorption 1

Portal Hypertensive Gastropathy

• Begin with oral iron supplements
• Consider IV iron if ongoing bleeding and poor response to oral therapy
• Consider nonselective β-blockers to treat portal hypertension 1

Celiac Disease

• Ensure adherence to gluten-free diet to improve iron absorption
• Use oral iron supplementation based on severity of deficiency
• Consider IV iron if iron stores don't improve 1

Common Pitfalls and Caveats

• Failure to investigate the underlying cause, especially in men and postmenopausal women
• Inadequate duration of therapy (should continue for 3 months after anemia correction)
• Poor compliance due to GI side effects (consider alternate-day dosing or different preparations)
• Missing celiac disease as a cause of iron malabsorption
• Failure to recognize that inflammatory conditions may mask iron deficiency with falsely normal ferritin
• Not considering IV iron when oral therapy fails or is inappropriate

By following this structured approach to diagnosis and treatment, most patients with iron deficiency anemia can achieve resolution of anemia and replenishment of iron stores, with significant improvements in quality of life and reduction in morbidity.