What is the best management approach for iron deficiency anemia?

Iron Deficiency Anemia: Management Overview

Start with oral ferrous sulfate 200 mg once daily—it is the most cost-effective first-line treatment with no therapeutic advantage of any other oral formulation. 1

Diagnosis

• Ferritin <45 ng/mL in non-inflamed patients or ferritin 46-99 ng/mL with transferrin saturation <20% confirms iron deficiency anemia 2
• In patients with inflammation (elevated CRP), use ferritin <100 ng/mL as the diagnostic threshold 3
• Iron saturation <20% indicates severe iron depletion requiring aggressive treatment 3

First-Line Oral Iron Therapy

• Ferrous sulfate 200 mg (65 mg elemental iron) once daily is the preferred formulation due to lowest cost and equal efficacy to all other oral preparations 1, 3
• Give iron once daily at most—never multiple times per day, as once-daily or alternate-day dosing improves tolerability while maintaining equal or superior absorption 1
• Alternative formulations (ferrous gluconate, ferrous fumarate) are equally effective but more expensive; use only if ferrous sulfate is not tolerated 1, 3
• Add vitamin C 500 mg with each iron dose to enhance absorption, particularly critical in patients with low iron saturation 1, 3
• Take on empty stomach for optimal absorption, though taking with food is acceptable if gastrointestinal side effects occur 3

Expected Response and Monitoring

• Hemoglobin should rise by approximately 2 g/dL after 3-4 weeks of treatment 1, 3
• Recheck hemoglobin at 4 weeks; failure to rise by 2 g/dL indicates poor compliance, continued blood loss, or malabsorption 3
• Continue oral iron therapy for 3 months after hemoglobin normalizes to fully replenish iron stores 1, 3
• Monitor hemoglobin and red cell indices every 3 months for the first year, then again after another year 1, 3

Indications for Intravenous Iron

Switch to IV iron when oral therapy fails or is contraindicated: 1, 3

• Intolerance to at least two different oral iron preparations 1, 3
• Failure of ferritin levels to improve after 4 weeks of compliant oral therapy 1
• Inflammatory bowel disease with active inflammation, especially if hemoglobin <10 g/dL 1, 3
• Post-bariatric surgery patients with disrupted duodenal iron absorption 1, 3
• Celiac disease with inadequate response to oral iron despite gluten-free diet adherence 1
• Ongoing gastrointestinal blood loss exceeding oral replacement capacity 3

Intravenous Iron Formulations

• Choose IV iron preparations that replace iron deficits in 1-2 infusions rather than multiple infusions 1
• Ferric carboxymaltose (500-1000 mg single doses, delivered within 15 minutes) is preferred for convenience 3
• Iron sucrose 200 mg can be given undiluted over 2-5 minutes or diluted in 100 mL normal saline over 15 minutes 4
• All IV iron formulations have similar safety profiles; true anaphylaxis is very rare (<1%) 1, 2
• Most reactions are complement activation-related pseudo-allergy (infusion reactions), not true anaphylaxis 1
• Always administer IV iron in medical facilities with resuscitation capabilities available 1, 5

Investigation of Underlying Cause

In premenopausal women <50 years: 1, 3

• Screen for celiac disease with tissue transglutaminase antibody (IgA type) and total IgA 1, 6
• Assess menstrual blood loss first, as menorrhagia accounts for iron deficiency in 5-10% of menstruating women 3
• Upper GI endoscopy only if upper GI symptoms present 1, 3
• Colonoscopy only if rectal bleeding, family history of colon cancer, or alarm symptoms present 1, 3

In men and postmenopausal women: 1, 6

• Perform bidirectional endoscopy (gastroscopy and colonoscopy) 1, 6
• Screen for celiac disease with tissue transglutaminase antibody 1, 6
• Test for Helicobacter pylori infection 2

Special Population Considerations

Inflammatory Bowel Disease: 1

• Determine whether iron deficiency is from inadequate intake/absorption or gastrointestinal bleeding 1
• Treat active inflammation first to enhance iron absorption and reduce iron depletion 1
• Use IV iron as first-line treatment when hemoglobin <10 g/dL with active inflammation 1, 3

Post-Bariatric Surgery: 1

• IV iron is preferred due to disrupted duodenal absorption mechanisms 1, 3

Celiac Disease: 1

• Ensure strict adherence to gluten-free diet to improve iron absorption 1
• Start with oral iron supplementation based on severity 1
• Progress to IV iron if oral supplementation fails despite dietary compliance 1

Portal Hypertensive Gastropathy: 1

• Start with oral iron supplements initially 1
• Switch to IV iron if ongoing bleeding persists without response to oral therapy 1
• Consider nonselective β-blockers to treat portal hypertension if no other source of chronic blood loss identified 1

Gastric Antral Vascular Ectasia: 1

• If inadequate response to iron replacement, consider endoscopic therapy with band ligation or argon plasma coagulation 1

Pregnant Women: 3

• Start oral low-dose iron 30 mg/day at first prenatal visit for prevention 3
• Treat anemia with 60-120 mg/day elemental iron 3
• Refer for further evaluation if hemoglobin <9.0 g/dL 3

Common Pitfalls to Avoid

• Do not prescribe multiple daily doses of oral iron—this increases side effects without improving efficacy 1, 3
• Do not stop iron therapy when hemoglobin normalizes—continue for 3 months to replenish stores 1, 3
• Do not continue oral iron indefinitely without response—reassess after 4 weeks and switch to IV iron if hemoglobin fails to rise 3
• Do not overlook vitamin C supplementation when oral iron response is suboptimal 1, 3
• Do not fail to identify and treat the underlying cause while supplementing iron 3, 6
• Avoid iron dextran preparations due to higher risk of anaphylaxis requiring test doses 3

Failure to Respond

• If no improvement after 4 weeks, assess for non-adherence, malabsorption, or ongoing blood loss 2
• If anemia does not resolve within 6 months despite appropriate therapy, reassess for ongoing blood loss 1, 3
• Evaluate for malabsorption syndromes (celiac disease, atrophic gastritis, chronic inflammation) 6
• Consider further gastrointestinal investigation including small bowel evaluation with capsule endoscopy if red flags present (weight loss, abdominal pain, elevated CRP) 6
• Verify patient adherence to therapy 3