What is the recommended treatment for iron deficiency anemia due to low iron storage?

Treatment of Iron Deficiency Anemia Due to Low Iron Storage

Start oral ferrous sulfate 200 mg once daily on an empty stomach, continue for 3 months after hemoglobin normalizes to replenish iron stores, and switch to intravenous iron only if the patient fails at least two different oral formulations or has specific malabsorption conditions. 1

First-Line Oral Iron Therapy

Ferrous sulfate 200 mg once daily is the preferred initial treatment due to its effectiveness and low cost. 1 This provides approximately 65 mg of elemental iron per dose. 2

Dosing Strategy

• Once-daily dosing is superior to multiple daily doses because it improves tolerability while maintaining effectiveness and maximizes fractional iron absorption. 1, 3
• Take on an empty stomach for optimal absorption, though taking with food is acceptable if gastrointestinal side effects occur. 1
• If side effects develop, switch to alternate-day dosing (every 48 hours) rather than reducing the daily dose, as this maintains absorption while reducing gut irritation. 3
• Morning dosing is preferred over afternoon or evening administration because the circadian increase in hepcidin is augmented by morning iron doses, reducing absorption from later doses. 3

Enhancing Absorption

• Add vitamin C (ascorbic acid) 500 mg with each iron dose to enhance absorption, particularly important when response is suboptimal. 1, 3
• Doses ≥60 mg stimulate an acute hepcidin increase that persists 24 hours but subsides by 48 hours, which is why alternate-day dosing can be more effective. 3

Alternative Oral Formulations

• Ferrous gluconate or ferrous fumarate are equally effective alternatives if ferrous sulfate is not tolerated. 1, 4
• These formulations may have better gastrointestinal tolerability in some patients. 5

Expected Response and Monitoring

• Hemoglobin should rise by approximately 2 g/dL after 3-4 weeks of treatment. 1, 6
• If no response occurs within 4 weeks despite compliance and absence of acute illness, assess for non-adherence, malabsorption, or ongoing blood loss. 7, 1
• Continue oral iron therapy for 3 months after anemia correction to fully replenish iron stores. 1, 5
• Monitor hemoglobin and red cell indices every 3 months for the first year, then again after another year. 1

When to Switch to Intravenous Iron

Intravenous iron should replace oral therapy in specific clinical scenarios:

Absolute Indications

• Intolerance to at least two different oral iron preparations despite trying alternate-day dosing. 1, 6
• Inflammatory bowel disease with active inflammation, especially if hemoglobin <10 g/dL. 1, 6
• Post-bariatric surgery patients due to disrupted duodenal iron absorption. 1, 6
• Celiac disease with inadequate response to oral iron despite strict gluten-free diet adherence. 1, 6
• Ongoing gastrointestinal blood loss exceeding oral replacement capacity. 1
• Second and third trimesters of pregnancy if oral iron is ineffective or not tolerated. 1, 6

Relative Indications

• Chronic kidney disease (particularly dialysis-dependent). 4
• Heart failure with iron deficiency. 6, 4
• Cancer-related iron deficiency. 6
• Severe anemia requiring rapid hemoglobin increase. 4

IV Iron Formulations

• Prefer IV iron formulations that can replace iron deficits with 1-2 infusions for patient convenience. 1
• Iron dextran can be given as total dose infusion but carries higher anaphylaxis risk. 1

Special Population Considerations

Pregnant Women

• Start 30 mg/day oral iron at first prenatal visit for primary prevention. 7
• Increase to 60-120 mg/day for treatment of anemia. 7
• Refer for further evaluation if hemoglobin <9.0 g/dL or hematocrit <27.0%. 7
• When hemoglobin normalizes for gestational stage, decrease to 30 mg/day. 7

Adolescent Girls and Women of Childbearing Age

• Treat with 60-120 mg/day oral iron and counsel about dietary iron sources. 7
• Continue treatment for 2-3 additional months after anemia correction. 7
• Screen annually if risk factors present (heavy menstrual bleeding, low iron intake, previous iron deficiency). 7

Inflammatory Bowel Disease

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

Identifying and Treating Underlying Causes

Always investigate the source of iron deficiency while initiating supplementation:

• Assess menstrual blood loss in premenopausal women. 1
• Perform gastrointestinal evaluation with upper endoscopy and colonoscopy in men and postmenopausal women. 1
• Screen for celiac disease with antiendomysial antibody and IgA measurement. 1
• Evaluate for chronic inflammatory conditions (inflammatory bowel disease, chronic kidney disease, heart failure). 6
• Assess for medication-related causes (nonsteroidal anti-inflammatory drugs, proton pump inhibitors). 6

Common Pitfalls to Avoid

• Do not prescribe multiple daily doses (e.g., three times daily), as this increases side effects without improving efficacy and reduces fractional absorption due to hepcidin elevation. 1, 3
• Do not stop iron therapy when hemoglobin normalizes - continue for 3 months to replenish stores. 1, 5
• Do not continue oral iron indefinitely without response - reassess after 4 weeks and switch to IV iron if hemoglobin fails to rise by 1 g/dL. 7, 1
• 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. 1, 8
• Do not use parenteral iron as first-line unless specific contraindications to oral therapy exist. 1, 6

Failure to Respond

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

• Reassess for ongoing blood loss. 1
• Evaluate for malabsorption syndromes (celiac disease, atrophic gastritis, Helicobacter pylori infection). 1, 6
• Verify patient adherence to therapy. 1
• Perform additional laboratory tests including MCV, RDW, and serum ferritin. 7
• In patients of African, Mediterranean, or Southeast Asian ancestry, consider thalassemia minor or sickle cell trait. 7
• Consider hematology consultation for complex cases. 1