What is the recommended treatment for severe iron deficiency anemia?

Treatment of Severe Iron Deficiency Anemia

For severe iron deficiency anemia (hemoglobin <10 g/dL), intravenous iron therapy is the preferred first-line treatment, as it provides rapid correction without the gastrointestinal side effects and slow response associated with oral iron. 1

Defining Severe Anemia and Initial Treatment Choice

• Severe anemia is defined as hemoglobin <10 g/dL (or <9 g/dL in pregnant women), which warrants immediate consideration of intravenous iron therapy 1
• The European Crohn's and Colitis Organisation specifically recommends IV iron as first-line treatment when hemoglobin is below 10 g/dL, particularly in the presence of active inflammation or malabsorption 1
• Oral iron therapy (ferrous sulfate 60-120 mg daily) can be attempted in hemodynamically stable patients with severe anemia, but IV iron should be used if no response occurs within 4 weeks 1, 2

Intravenous Iron: Preferred Formulations and Dosing

Ferric carboxymaltose is the preferred IV iron formulation because it allows delivery of 750-1000 mg of iron in a single 15-minute infusion, compared to older formulations requiring multiple visits 1, 3

Specific Dosing for Ferric Carboxymaltose (Injectafer):

• For patients ≥50 kg: 750 mg IV on day 1, repeat in 7 days (total 1500 mg per course) 3
• Alternative single-dose regimen: 15 mg/kg up to maximum 1000 mg IV as single dose 3
• For patients <50 kg: 15 mg/kg IV on day 1, repeat in 7 days 3
• Administration time is 15 minutes minimum for doses up to 1000 mg 3

Other IV Iron Options:

• Iron sucrose requires multiple smaller doses (200 mg two to three times weekly), making it less convenient 4
• Avoid iron dextran preparations due to higher anaphylaxis risk requiring test doses 2

Expected Response and Monitoring

• Hemoglobin should increase by approximately 2 g/dL after 3-4 weeks of treatment 1, 2
• If hemoglobin fails to rise by 1 g/dL (or hematocrit by 3%) after 4 weeks despite compliance, further evaluation is required including MCV, RDW, and serum ferritin 1
• Check for ongoing blood loss, malabsorption syndromes (celiac disease, atrophic gastritis), or hemoglobinopathies (thalassemia minor, sickle cell trait in patients of African, Mediterranean, or Southeast Asian ancestry) 1, 5

When Oral Iron May Be Considered

Oral iron can be attempted in hemodynamically stable patients without active inflammation or malabsorption, but only if close monitoring is feasible 1, 2

Oral Iron Regimen:

• Ferrous sulfate 200 mg once daily (preferred over multiple daily doses for better tolerability) 2
• Add vitamin C 500 mg with each iron dose to enhance absorption 2
• Alternative formulations (ferrous gluconate, ferrous fumarate) if ferrous sulfate not tolerated 2
• Continue for 3 months after hemoglobin normalizes to replenish iron stores 1, 2

Absolute Indications for IV Iron (Not Oral)

The following conditions mandate IV iron therapy, not oral iron 1, 2:

• Hemoglobin <10 g/dL with active inflammatory bowel disease 1
• Post-bariatric surgery patients (disrupted duodenal absorption) 1
• Celiac disease with inadequate response to oral iron despite gluten-free diet 1
• Intolerance to at least two different oral iron preparations 1, 2
• Ongoing gastrointestinal blood loss exceeding oral replacement capacity 2
• Acute anemia with hemodynamic instability 1

Special Population Considerations

Pregnant Women with Severe Anemia:

• If hemoglobin <9.0 g/dL, refer to physician familiar with anemia in pregnancy for further evaluation 1
• Start with oral iron 60-120 mg daily, but IV iron is indicated if no response after 4 weeks 1
• When hemoglobin normalizes for gestational age, decrease to 30 mg daily 1

Inflammatory Bowel Disease:

• Treat active inflammation first to enhance iron absorption and reduce iron depletion 1
• IV iron is first-line when hemoglobin <10 g/dL and clinically active disease is present 1

Chronic Kidney Disease (Non-Dialysis):

• Ferric carboxymaltose 750 mg IV repeated in 7 days is FDA-approved for this indication 3

Critical Safety Monitoring for IV Iron

Monitor for hypophosphatemia, especially with repeat courses within 3 months 1, 3:

• Check serum phosphate levels before repeat treatment 3
• Hypophosphatemia can cause bone pain, fractures, muscle weakness, and fatigue 3
• Treat hypophosphatemia as medically indicated before repeat dosing 3

Monitor for hypersensitivity reactions during and for 30 minutes after infusion 3:

• True anaphylaxis is very rare with modern IV iron formulations 1
• Most reactions are complement activation-related pseudo-allergy (infusion reactions) 1
• Have resuscitation equipment available 3

Common Pitfalls to Avoid

• Do not continue oral iron beyond 4 weeks without documented hemoglobin response—switch to IV iron 2
• Do not use multiple daily doses of oral iron—once-daily dosing has similar efficacy with better tolerability 2
• Do not stop iron therapy when hemoglobin normalizes—continue for 3 months to replenish stores 2
• Do not overlook vitamin C supplementation when using oral iron—it significantly enhances absorption 2
• Do not fail to identify and treat the underlying cause while supplementing iron 2, 5
• Do not use intramuscular iron—it is painful, no more effective than oral, and carries anaphylaxis risk 1

Failure to Respond: Next Steps

If anemia persists at 6 months despite appropriate iron therapy 2:

• Reassess for ongoing occult blood loss (repeat endoscopy if indicated) 5
• Evaluate for malabsorption (celiac serology, consider gastroscopy with duodenal biopsies) 5
• Consider small bowel investigation (capsule endoscopy, CT/MRI enterography) if red flags present 5
• Screen for hemoglobinopathies in at-risk ethnic groups 1
• Consider hematology consultation for complex cases 2