A 79‑year‑old man on low‑dose aspirin (acetylsalicylic acid) has hemoglobin 8.4 g/dL (severe anemia), serum iron 3 µg/dL (very low), ferritin 43 µg/L (low) despite taking oral ferrous sulfate 300 mg daily; what are the next steps in management and, if intravenous iron is indicated, which formulation, dose, and interval should be used?

Management of Refractory Iron Deficiency Anemia in an Elderly Patient on Aspirin

Immediate Action: Discontinue Aspirin and Switch to IV Iron

Stop aspirin immediately and initiate intravenous iron therapy, as this patient has failed oral iron supplementation and aspirin itself is likely contributing to ongoing iron depletion through its chelating metabolites. 1, 2

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Why Oral Iron Has Failed

• Aspirin-induced iron depletion: Low-dose aspirin (even 75-100 mg daily) causes iron deficiency anemia in approximately 20% of elderly patients through its metabolites (salicyluric acid, salicylic acid, and dihydroxybenzoic acids), which chelate iron and increase urinary iron excretion—independent of gastrointestinal bleeding. 3, 2

• Inadequate response criteria: After one month of oral iron, hemoglobin should increase by 1-2 g/dL (10-20 g/L). 1, 4 This patient's hemoglobin of 8.4 g/dL (84 g/L) with ferritin of only 43 µg/L despite taking 300 mg ferrous sulfate daily indicates either non-adherence, malabsorption, or ongoing losses exceeding absorption. 1

• Hepcidin effect: Once-daily oral iron increases hepcidin levels for up to 48 hours, blocking further iron absorption—taking iron more frequently provides no benefit and increases side effects. 1

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Intravenous Iron: Formulation, Dose, and Interval

Preferred Formulation: Ferric Carboxymaltose (Ferinject/Injectafer)

Ferric carboxymaltose is the optimal choice because it allows complete iron repletion in 1-2 infusions, has the lowest anaphylaxis risk, and does not require a test dose. 1, 5

Dosing Regimen

For a patient weighing ≥50 kg: 5

• Week 0: Ferric carboxymaltose 750 mg IV over 15 minutes (or as slow IV push at 100 mg/minute)
• Week 1 (minimum 7 days later): Ferric carboxymaltose 750 mg IV over 15 minutes
• Total cumulative dose: 1,500 mg iron per course

Alternative single-dose option: If the patient weighs ≥50 kg, a single dose of 1,000 mg IV (maximum 15 mg/kg) can be given over 15 minutes, though the two-dose regimen is preferred for better tolerance. 5

Administration Details

• Dilute up to 1,000 mg in no more than 250 mL sterile 0.9% sodium chloride (minimum concentration 2 mg iron/mL). 5
• Infuse over at least 15 minutes. 5
• Monitor for hypersensitivity reactions during infusion and for 30 minutes post-infusion. 5
• Ensure resuscitation equipment is immediately available (true anaphylaxis is rare at 0.1%, but complement activation-related pseudo-allergy occurs in 1.5%). 1, 5

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Alternative IV Iron Formulations (If Ferric Carboxymaltose Unavailable)

Second Choice: Iron Isomaltoside or Iron Sucrose

• Iron sucrose (Venofer): 200 mg IV over 10 minutes, repeated 5-7 times (total 1,000-1,400 mg). 1
• Low molecular weight iron dextran (Infed): Can deliver 1,000 mg in a single infusion but requires a test dose due to higher anaphylaxis risk (0.6-0.7%). 1

Avoid high molecular weight iron dextran (Dexferrum)—it is off the market due to unacceptable adverse reaction rates. 1

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Critical Next Steps Beyond Iron Replacement

1. Investigate for Occult Blood Loss

Even though the patient is on aspirin, hemoglobin of 8.4 g/dL with serum iron of 3 µg/dL is severe and warrants evaluation for gastrointestinal malignancy: 4

• Colonoscopy (first-line in patients >50 years with iron deficiency anemia). 4
• Upper endoscopy if colonoscopy is negative or if upper GI symptoms are present. 1
• Celiac serology (tissue transglutaminase IgA) to exclude malabsorption. 1

2. Monitor Response to IV Iron

• Recheck hemoglobin 2 weeks after the first IV iron dose—expect a 1 g/dL increase. 1
• Recheck ferritin and hemoglobin at 1 month—ferritin should rise substantially. 1
• If hemoglobin and ferritin do not improve, consider bone marrow biopsy to exclude myelodysplastic syndrome or other marrow pathology. 6, 4

3. Avoid Common Pitfalls

• Do NOT continue oral iron once IV iron is initiated—it will not add benefit and increases side effects. 1
• Do NOT add vitamin C to IV iron therapy—it is only useful with oral iron to enhance absorption. 1
• Do NOT use erythropoiesis-stimulating agents (ESAs)—they are ineffective for iron deficiency anemia and contraindicated in elderly patients with cardiovascular risk. 6
• Do NOT restart aspirin until iron stores are repleted and the source of anemia is identified; if aspirin is medically necessary, consider switching to a proton pump inhibitor for gastroprotection or using alternative antiplatelet agents. 2

4. Monitor for Hypophosphatemia

• Check serum phosphate levels before any repeat course of IV iron (especially within 3 months), as ferric carboxymaltose can cause symptomatic hypophosphatemia, osteomalacia, and fractures. 5
• Treat hypophosphatemia if detected. 5

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Long-Term Monitoring

• Recheck hemoglobin and ferritin every 3 months for 1 year, then annually. 1
• If iron deficiency recurs, repeat IV iron (ferric carboxymaltose 750 mg × 2 doses separated by ≥7 days). 5
• If recurrent despite IV iron, escalate investigation for occult bleeding (consider video capsule endoscopy for small bowel evaluation). 1

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Summary Algorithm

1. Stop aspirin immediately. 2
2. Administer ferric carboxymaltose 750 mg IV at Week 0 and Week 1 (total 1,500 mg). 5
3. Check hemoglobin at 2 weeks (expect +1 g/dL) and ferritin at 1 month. 1
4. Perform colonoscopy and upper endoscopy to exclude GI malignancy. 4
5. Check celiac serology. 1
6. Monitor serum phosphate before any repeat IV iron course. 5
7. Recheck hemoglobin/ferritin every 3 months × 1 year, then annually. 1