What is the best first‑line treatment for iron‑deficiency anemia in a 54‑year‑old woman with anemia, reticulocytosis, uncontrolled type 2 diabetes, acute pyelonephritis on IV antibiotics, hospitalized with limited oral intake and on a proton‑pump inhibitor?

Treatment for Iron Deficiency Anemia with Hemoglobin 9.8 g/dL

Given this patient's acute pyelonephritis, limited oral intake, concurrent PPI use, and hemoglobin of 9.8 g/dL, intravenous iron is the preferred first-line treatment rather than oral iron. 1

Rationale for Intravenous Iron as First-Line

This patient has multiple factors that make oral iron ineffective or contraindicated:

• Active infection with inflammation: Acute pyelonephritis drives hepcidin elevation, which severely impairs intestinal iron absorption. 1
• Limited oral intake: The patient is hospitalized with poor oral intake, making oral iron therapy impractical. 1
• PPI use: Proton pump inhibitors reduce gastric acid secretion, impairing conversion of dietary non-heme iron to absorbable ferrous iron. 2
• Hemoglobin <10 g/dL with inflammation: This threshold is an absolute indication for IV iron in patients with active inflammatory conditions. 1

Recommended IV Iron Regimen

Ferric carboxymaltose 750–1000 mg administered intravenously over 15 minutes, with a second dose given at least 7 days later for a total cumulative dose of 1500 mg. 3

• This formulation allows complete iron repletion in 1–2 infusions, minimizing infusion-related risk and improving convenience. 1
• Alternative: Ferric derisomaltose 1000 mg as a single infusion. 1
• Avoid iron dextran as first-line due to higher anaphylaxis risk (0.6–0.7%). 1

Expected Response and Monitoring

• Hemoglobin should rise by approximately 2 g/dL within 3–4 weeks of IV iron administration. 1
• Recheck hemoglobin at 4 weeks; failure to achieve ≥1 g/dL rise warrants reassessment for ongoing blood loss or other causes. 1
• After hemoglobin normalizes, continue monitoring every 3 months for the first year. 1

Safety Considerations

• IV iron must be administered in a setting equipped with resuscitation equipment. 1
• Most infusion reactions are complement-activation pseudo-allergies (CARPA) that respond to slowing the infusion rate, not true anaphylaxis. 1
• Monitor serum phosphate levels, especially if repeat courses are needed within 3 months, as IV iron can cause hypophosphatemia. 3

Addressing Underlying Causes

This patient requires comprehensive investigation after acute infection resolves:

• Gastrointestinal evaluation: Upper endoscopy and colonoscopy are mandatory in a 54-year-old woman to exclude malignancy and identify bleeding sources. 1
• Celiac disease screening: Anti-endomysial antibody and IgA measurement should be performed, as 2–3% of iron-deficient patients have celiac disease. 1
• Helicobacter pylori testing: Eradication is recommended if positive, as it contributes to recurrent iron deficiency. 1
• Review PPI necessity: The indication for PPI should be reassessed annually, as prolonged use increases risk of recurrent iron deficiency. 2

Why Oral Iron Should NOT Be Used Initially

• Inflammation-driven hepcidin elevation from acute pyelonephritis blocks intestinal iron absorption, rendering oral iron ineffective. 1
• PPI-induced malabsorption further impairs oral iron uptake. 2
• Limited oral intake during acute illness makes adherence to oral therapy unreliable. 1
• Studies show IV iron achieves a higher likelihood of ≥2.0 g/dL hemoglobin increase (odds ratio 1.57) compared to oral iron in inflammatory conditions. 1

Transition to Oral Iron (If Appropriate Later)

Once the acute infection resolves, inflammation subsides, and oral intake improves, oral iron may be considered if IV iron is unavailable or declined:

• Ferrous sulfate 200 mg (65 mg elemental iron) once daily on an empty stomach. 1
• Add vitamin C 500 mg with each dose to enhance absorption, especially critical given the low transferrin saturation. 1
• Continue for 3 months after hemoglobin normalizes to replenish iron stores (total duration 6–7 months). 1

Critical Pitfalls to Avoid

• Do not prescribe oral iron in the acute setting with active infection and hemoglobin <10 g/dL; this is ineffective and delays appropriate treatment. 1
• Do not attribute iron deficiency solely to PPI use until complete gastrointestinal investigation excludes malignancy. 2
• Do not use multiple daily doses of oral iron if eventually prescribed; once-daily dosing is superior due to hepcidin-mediated absorption blockade. 1
• Do not discontinue iron therapy when hemoglobin normalizes; continue for 3 additional months to replenish stores. 1

Blood Transfusion Consideration

Transfusion is NOT indicated in this patient unless she develops severe symptomatic anemia with circulatory compromise (e.g., chest pain, severe dyspnea, hemodynamic instability). 1

• Target hemoglobin for transfusion is 70–90 g/L (7–9 g/dL) in stable patients. 1
• One unit of packed red cells provides only ~200 mg elemental iron; therefore, restrictive transfusion should be followed by IV iron replacement. 1