How to manage iron deficiency anemia in a patient with potential underlying chronic diseases, such as chronic kidney disease (CKD) or gastrointestinal disorders, and impaired iron absorption?

Management of Iron Deficiency Anemia

Start with oral ferrous sulfate 200 mg once daily, which is the preferred first-line treatment due to its effectiveness and low cost, and add vitamin C 500 mg to enhance absorption. 1, 2

Initial Oral Iron Therapy

• Ferrous sulfate is the preferred formulation because it is the least expensive option with no therapeutic advantage of any other oral iron preparation 1, 2
• Prescribe ferrous sulfate 200 mg (containing 65 mg elemental iron) once daily—never multiple times per day 1, 2
• Once-daily dosing improves tolerance while maintaining equal or better iron absorption compared to multiple daily doses due to hepcidin regulation 1, 2
• Every-other-day dosing may be better tolerated for some patients with similar rates of iron absorption 1
• Add vitamin C (ascorbic acid) 500 mg with each iron dose to improve absorption 1, 2
• Alternative formulations (ferrous fumarate or ferrous gluconate) are equally effective if ferrous sulfate is not tolerated 1, 2

Expected Response and Monitoring

• Check hemoglobin at 4 weeks, expecting a rise of approximately 2 g/dL 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
• If no hemoglobin rise occurs within 4 weeks, assess for non-adherence, malabsorption, or ongoing blood loss 2

When to Switch to Intravenous Iron

Use intravenous iron if the patient does not tolerate oral iron, ferritin levels do not improve with a trial of oral iron, or the patient has a condition in which oral iron is not likely to be absorbed. 1

Specific Indications for IV Iron:

• Intolerance to at least two different oral iron preparations 1, 2
• Failure of ferritin levels to improve after 4 weeks of compliant oral therapy 2
• Active inflammatory bowel disease with hemoglobin <10 g/dL 1, 2
• Post-bariatric surgery patients with disrupted duodenal iron absorption 1, 2
• Celiac disease with inadequate response to oral iron despite gluten-free diet adherence 1, 2
• Ongoing gastrointestinal blood loss exceeding oral replacement capacity 2
• Chronic kidney disease with functional iron deficiency (ferritin 100-300 ng/mL with transferrin saturation <20%) 1, 3
• Chronic heart failure with iron deficiency (ferritin <100 ng/mL or 100-300 ng/mL with transferrin saturation <20%) 1

Intravenous Iron Formulations

• Prefer IV iron formulations that can replace iron deficits with 1-2 infusions rather than those requiring more than 2 infusions 1, 2
• Ferric carboxymaltose can deliver 500-1000 mg in a single dose within 15 minutes 2, 4
• Iron dextran can be given as a total dose infusion but requires resuscitation facilities available 2
• Iron sucrose requires multiple visits with maximum 200 mg per infusion 5
• All IV iron formulations have similar overall safety profiles; true anaphylaxis is very rare (0.6-0.7%) 1, 2
• Most reactions are complement activation-related pseudo-allergy (infusion reactions) that respond to slowing the infusion rate 1

Special Population Considerations

Inflammatory Bowel Disease:

• Determine whether iron deficiency is due to inadequate intake/absorption or gastrointestinal bleeding 1
• Treat active inflammation effectively to enhance iron absorption or reduce iron depletion 1, 2
• Use IV iron as first-line treatment when hemoglobin <10 g/dL with active inflammation 1, 2
• Monitor for recurrent iron deficiency every 3 months for at least a year after correction 1

Chronic Kidney Disease:

• Functional iron deficiency is common and defined by ferritin 100-300 ng/mL with transferrin saturation <20% 1, 3
• Absolute iron deficiency is defined by transferrin saturation ≤20% and ferritin ≤100 ng/mL (predialysis/peritoneal dialysis) or ≤200 ng/mL (hemodialysis) 3
• IV iron is preferred for dialysis patients; either IV or oral iron for non-dialysis CKD stages 3-5 3
• Refer to nephrology-specific guidelines for detailed management 1

Chronic Heart Failure:

• Screen for iron deficiency with ferritin and transferrin saturation 1
• IV iron improves symptoms and quality of life in heart failure with functional iron deficiency 1
• No prognostic benefit has been demonstrated for oral iron in heart failure 1
• Avoid oral iron as it may be poorly absorbed due to gut edema and causes frequent side effects 1

Post-Bariatric Surgery:

• IV iron is preferred due to disrupted duodenal absorption mechanisms 1, 2
• Do not preclude search for other causes of iron deficiency despite surgical history 1

Celiac Disease:

• Ensure adherence to gluten-free diet to improve iron absorption 1, 2
• Consider oral iron supplementation based on severity of iron deficiency and patient tolerance 1
• Progress to IV iron if iron stores do not improve despite dietary compliance 1, 2

Portal Hypertensive Gastropathy:

• Initially use oral iron supplements to replenish iron stores 1
• Use IV iron in patients with ongoing bleeding who do not respond to oral iron 1
• Consider treatment of portal hypertension with nonselective β-blockers 1

Gastric Antral Vascular Ectasia:

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

Critical Pitfalls to Avoid

• Do not prescribe multiple daily doses of oral iron—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 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 of iron deficiency while supplementing 2
• Do not defer iron replacement therapy while awaiting investigations unless colonoscopy is imminent 1

Failure to Respond

• If anemia does not resolve within 6 months despite appropriate iron therapy, reassess for ongoing blood loss 2
• Evaluate for malabsorption syndromes 2
• Consider further gastrointestinal investigation 2
• Verify patient adherence to therapy 2
• Consider hematology consultation for complex cases 2