What is the initial treatment and management approach for a patient with iron deficiency anemia?

Iron Deficiency Anemia: Initial Treatment and Management

Immediate Treatment Initiation

Start oral ferrous sulfate 200 mg (65 mg elemental iron) once daily immediately—do not delay treatment while awaiting diagnostic workup unless colonoscopy is scheduled within days. 1

• Ferrous sulfate is the preferred formulation due to lowest cost with equal efficacy to all other oral iron preparations 1, 2
• Once-daily dosing is superior to multiple daily doses—it improves tolerance while maintaining equal or better iron absorption due to hepcidin regulation 1
• Alternative formulations (ferrous fumarate 106 mg elemental iron or ferrous gluconate 38 mg elemental iron) are equally effective if ferrous sulfate is not tolerated 1, 2

Optimize Absorption

• Add vitamin C (ascorbic acid) 500 mg with each iron dose to enhance absorption 1, 2
• Take on empty stomach for optimal absorption, though taking with food is acceptable if gastrointestinal side effects occur 2
• If not tolerated daily, switch to every-other-day dosing, which increases fractional iron absorption and improves tolerance with similar efficacy 1

Expected Response and Monitoring

• Check hemoglobin at 4 weeks—expect a rise of approximately 2 g/dL 1, 2
• If hemoglobin fails to rise by 2 g/dL at 4 weeks, assess for non-adherence, ongoing blood loss, or malabsorption 1, 2
• Continue oral iron for 3 months after hemoglobin normalizes to fully replenish iron stores 1, 2
• Monitor hemoglobin and red cell indices every 3 months for the first year, then again after another year 1, 2

When to Switch to Intravenous Iron

Switch to IV iron if any of the following criteria are met:

• Intolerance to at least two different oral iron preparations 1, 2
• No improvement in ferritin levels after 4 weeks of compliant oral therapy 1, 2
• Active inflammatory bowel disease with hemoglobin <10 g/dL 1, 2
• Post-bariatric surgery patients (disrupted duodenal absorption) 1, 2
• Celiac disease with inadequate response despite gluten-free diet adherence 1, 2
• Ongoing gastrointestinal blood loss exceeding oral replacement capacity 2

IV Iron Formulation Selection

• Choose IV iron preparations that replace iron deficits in 1-2 infusions (ferric carboxymaltose 500-1000 mg, can be delivered within 15 minutes) 1, 2
• Avoid iron dextran due to higher anaphylaxis risk requiring test doses 2
• True anaphylaxis to modern IV iron formulations is very rare (<1%); most reactions are complement activation-related pseudo-allergy (infusion reactions) 1, 3

Investigate Underlying Cause Simultaneously

In premenopausal women <40 years:

• Assess menstrual blood loss first—menorrhagia accounts for iron deficiency in 5-10% of menstruating women 2
• Screen for celiac disease with antiendomysial antibody and IgA measurement 2, 4
• Bidirectional endoscopy (gastroscopy and colonoscopy) is not routinely required unless heavy menstrual bleeding is excluded or alarm symptoms present 4

In men and postmenopausal women:

• Perform bidirectional endoscopy (gastroscopy and colonoscopy) to exclude gastrointestinal malignancy 4, 5
• Screen for celiac disease with antiendomysial antibody and IgA measurement 2, 4
• Test for Helicobacter pylori infection 3
• Upper gastrointestinal cancer is 1/7 as common as colon cancer in this population 4

After negative bidirectional endoscopy:

• Small bowel investigation (capsule endoscopy, CT/MR enterography) is only indicated if ongoing IDA persists after iron replacement therapy or if red flags present (involuntary weight loss, abdominal pain, elevated CRP) 1, 4
• Capsule endoscopy is the preferred test for small bowel examination due to higher diagnostic yield for mucosal lesions 1

Special Population Considerations

Inflammatory bowel disease:

• Treat active inflammation first to enhance iron absorption and reduce iron depletion 1, 2
• Use IV iron as first-line if hemoglobin <10 g/dL with active inflammation 1, 2

Post-bariatric surgery:

• IV iron is preferred due to disrupted duodenal absorption mechanisms 1, 2

Celiac disease:

• Ensure strict adherence to gluten-free diet to improve iron absorption 1, 2
• Progress to IV iron if oral supplementation fails despite dietary compliance 1, 2

Portal hypertensive gastropathy:

• Start with oral iron supplementation initially 1
• Switch to IV iron if ongoing bleeding persists without response to oral therapy 1

Critical Pitfalls to Avoid

• Do not prescribe multiple daily doses—this increases side effects without improving efficacy due to hepcidin-mediated absorption blockade 1
• Do not stop iron therapy when hemoglobin normalizes—continue for 3 months to replenish stores 1, 2
• Do not continue oral iron indefinitely without response—reassess at 4 weeks and switch to IV iron if no hemoglobin rise 1, 2
• Do not overlook vitamin C supplementation when oral iron response is suboptimal 1, 2
• Do not fail to identify and treat the underlying cause while supplementing iron 2, 4

Failure to Respond

If anemia does not resolve within 6 months despite appropriate therapy:

• Reassess for ongoing blood loss 2, 4
• Evaluate for malabsorption syndromes (celiac disease, atrophic gastritis, chronic inflammation) 4, 3
• Consider further gastrointestinal investigation with capsule endoscopy 1, 4
• Verify patient adherence to therapy 2, 3
• Consider hematology consultation for complex cases 2