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

Management of Iron Deficiency Anemia

First-Line Treatment: Oral Iron

Start ferrous sulfate 200 mg (65 mg elemental iron) once daily immediately upon diagnosis—this is the preferred first-line treatment due to superior cost-effectiveness and equivalent efficacy to all other oral formulations 1, 2.

Optimizing Oral Iron Therapy

• Take iron on an empty stomach for optimal absorption, though taking with food is acceptable if gastrointestinal side effects occur 1
• Add vitamin C (ascorbic acid) 500 mg with each iron dose to enhance absorption, particularly critical when transferrin saturation is severely low 1, 2
• Never prescribe multiple daily doses—once-daily dosing improves tolerance while maintaining equal or better absorption due to hepcidin regulation that blocks iron uptake for 48 hours after each dose 1
• If once-daily dosing is not tolerated, alternate-day dosing increases fractional iron absorption with similar efficacy and better tolerance 1

Alternative Oral Formulations

• Ferrous gluconate or ferrous fumarate are equally effective if ferrous sulfate causes intolerable side effects (constipation, diarrhea, nausea), though they offer no proven superiority in tolerability 1, 3
• All oral iron formulations have equivalent therapeutic efficacy—the choice is purely economic, with ferrous sulfate being consistently the least expensive 1

Expected Response and Monitoring

• Check hemoglobin at 4 weeks, expecting a rise of approximately 2 g/dL 1, 2
• If hemoglobin fails to rise by 2 g/dL after 4 weeks, assess for non-adherence, malabsorption, ongoing blood loss, or inflammatory conditions 1
• Continue oral iron for 3 months after hemoglobin normalizes to fully replenish iron stores—total treatment duration typically 6-7 months 1, 2
• Monitor hemoglobin and red cell indices every 3 months for the first year after completing therapy, then again after another year 1

When to Switch to Intravenous Iron

Use intravenous iron as first-line therapy or switch from oral iron in the following specific scenarios 1, 4:

Absolute Indications for IV Iron

• Active inflammatory bowel disease with hemoglobin <10 g/dL—inflammation-induced hepcidin elevation severely impairs oral iron absorption, making IV iron first-line treatment 1, 2
• Post-bariatric surgery patients—disrupted duodenal absorption mechanisms render oral iron ineffective 1, 4
• Intolerance to at least two different oral iron preparations (must have tried ferrous sulfate plus one alternative formulation) 1, 2
• Failure of ferritin levels to improve after 4 weeks of compliant oral therapy 1
• Ongoing gastrointestinal blood loss exceeding oral replacement capacity 1
• Second and third trimesters of pregnancy when oral iron fails or is not tolerated 1, 4

Relative Indications for IV Iron

• Celiac disease with inadequate response to oral iron despite strict gluten-free diet adherence 1, 4
• Chronic kidney disease with functional iron deficiency (ferritin 100-300 ng/mL with transferrin saturation <20%) 1
• Chronic heart failure with iron deficiency (ferritin <100 ng/mL or 100-300 ng/mL with transferrin saturation <20%)—IV iron improves symptoms and quality of life 1, 4
• Severe symptomatic anemia with circulatory compromise requiring rapid correction 1

Preferred IV Iron Formulations

• Choose IV iron preparations that replace iron deficits in 1-2 infusions rather than multiple infusions to minimize risk and improve convenience 1
• Ferric carboxymaltose (500-1000 mg single doses delivered within 15 minutes) is a preferred formulation 1
• Iron sucrose can be administered as 200 mg undiluted over 2-5 minutes or diluted in 100 mL normal saline over 15 minutes 5
• Ferric gluconate is FDA-approved for iron deficiency anemia in chronic kidney disease patients on hemodialysis receiving erythropoietin 6
• Avoid iron dextran when possible due to higher risk of anaphylaxis, though true anaphylaxis with any IV iron formulation is rare (0.6-0.7%) 1

Special Population Considerations

Inflammatory Bowel Disease

• Treat active inflammation first to enhance iron absorption and reduce iron depletion 1
• Use IV iron as first-line when hemoglobin <10 g/dL with active inflammation—IV iron is more effective (odds ratio 1.57 for achieving 2.0 g/dL hemoglobin increase) and better tolerated than oral iron in IBD 1
• For mild anemia (hemoglobin >10 g/dL) with clinically inactive disease, oral iron may be appropriate if disease is truly quiescent 1

Pregnant Women

• Start oral low-dose iron 30 mg/day at first prenatal visit for prevention 1
• Treat anemia with 60-120 mg/day elemental iron 1
• Refer for further evaluation if hemoglobin <9.0 g/dL 1
• Use IV iron during second and third trimesters if oral iron fails or is not tolerated 1, 4

Celiac Disease

• Ensure strict adherence to gluten-free diet to improve iron absorption 1, 4
• Screen all patients with iron deficiency for celiac disease with antiendomysial antibody and IgA measurement, regardless of age 2
• Progress to IV iron if iron stores do not improve despite dietary compliance 1

Chronic Kidney Disease and Heart Failure

• Functional iron deficiency is common in CKD (ferritin 100-300 ng/mL with transferrin saturation <20%) 1
• IV iron is preferred for dialysis patients; either IV or oral iron for non-dialysis CKD stages 3-5 1
• Screen heart failure patients for iron deficiency with ferritin and transferrin saturation 1

Identifying and Treating Underlying Causes

Premenopausal Women

• Assess menstrual blood loss first—menorrhagia, pregnancy, and breastfeeding account for iron deficiency in 5-10% of menstruating women 1
• Consider pictorial blood loss assessment charts (80% sensitivity and specificity for detecting menorrhagia) 1
• Women under 45 years without upper GI symptoms do not routinely need upper endoscopy but should have celiac screening 2

Men and Postmenopausal Women

• Perform gastrointestinal evaluation with upper endoscopy and colonoscopy—these populations require full investigation for occult bleeding 1, 4
• Women over 45 years require full gastrointestinal investigation as risk of serious pathology increases significantly with age 2

Critical Pitfalls to Avoid

• Do not prescribe multiple daily doses—this increases side effects without improving efficacy due to hepcidin-mediated absorption blockade 1, 2
• 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 after 4 weeks and switch to IV iron if hemoglobin fails to rise 1
• Do not prescribe oral iron to patients with active inflammatory bowel disease, especially if hemoglobin <10 g/dL—this is ineffective and potentially harmful 1
• 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 1, 2
• Do not exceed 200 mg elemental iron daily—higher doses increase side effects and paradoxically reduce absorption due to hepcidin elevation 2
• Do not defer iron replacement while awaiting investigations unless colonoscopy is imminent, as iron can interfere with visualization 1

Failure to Respond

If anemia does not resolve within 6 months despite appropriate iron therapy 1:

• Reassess for ongoing blood loss 1
• Evaluate for malabsorption syndromes 1
• Consider further gastrointestinal investigation 1
• Verify patient adherence to therapy 1
• Consider hematology consultation for complex cases 1