Treatment of Iron Deficiency Anemia (IDA)

1. Treat the Underlying Cause

2. Oral Iron Therapy (First-Line)

Preparations and Elemental Iron Content

• Ferrous salts are absorbed ~3x better than ferric salts
• Ferrous sulfate, fumarate, and gluconate are all equally effective

Dosing

• Adults: 60-100 mg elemental iron BID PO (up to 60 mg QID for rapid repletion). A common regimen is ferrous sulfate 325 mg once daily on an empty stomach for maximal absorption
• Children (3-12 yr): 3-6 mg elemental Fe/kg/day divided BID-TID PO
• Premature infants: 2-4 mg elemental Fe/kg/day, max 15 mg/day
• Pregnancy: 30-60 mg elemental Fe/day (prophylaxis); higher doses for established IDA

Modern note: Higher doses (150-200 mg/day) are not clearly superior to lower doses (40-80 mg/day). Increasing oral iron dose paradoxically decreases absorption (via hepcidin upregulation). Every-other-day dosing is emerging as equally effective with fewer side effects.

How Long to Treat?

• Hemoglobin typically rises ~2 g/L/day with adequate treatment; red cell mass reconstituted in 1-2 months
• Continue therapy for 3-6 months after Hb normalizes to replenish stores (stores build at ~100 mg/month)

Tips to Improve Absorption

• Take on an empty stomach
• Ascorbic acid (vitamin C, ≥200 mg per dose) boosts absorption by ≥30%
• Avoid concurrent antacids, tetracyclines, or dairy (reduce absorption)
• Less GI irritation if taken with food (but absorption is reduced)

Side Effects

3. Parenteral (IV) Iron - When to Use

• Failure to respond to oral iron (no Hb rise within 2 weeks)
• Intolerance to oral iron (persistent GI side effects)
• Malabsorption: celiac disease, inflammatory bowel disease, short bowel, bariatric surgery, H. pylori
• Ongoing blood loss exceeding oral iron absorption capacity
• Chronic kidney disease (CKD) patients on erythropoietin
• Pregnancy (IV iron shown superior to oral)
• Patients on total parenteral nutrition

IV Iron Formulations

• Parenteral iron can replete stores in 1-2 sessions vs. months with oral therapy
• Formulas to calculate total iron deficit are unreliable; monitor response clinically and with Hb/ferritin

IV Iron Safety

• Reactions are complement activation-related pseudoallergy (not true allergy) - test dose is NOT helpful for preventing reactions
• Mild reactions: ~1 in 200 (slow the infusion)
• Major reactions: ~1 in 200,000
• Observe all patients for 30 min post-infusion
• Avoid diphenhydramine premedication (worsens reactions)
• For severe reactions: stop infusion, give IV fluids + hydrocortisone 150-500 mg; anaphylaxis requires epinephrine + oxygen
• Ferric carboxymaltose causes hypophosphatemia in ~75% of recipients (symptomatic in some) - monitor phosphate
• Ferumoxytol can act as MRI contrast agent - inform radiologists

4. Adjuncts

• Erythropoietin (EPO/darbepoetin): Used in CKD or chemotherapy-related anemia, NOT for IDA alone. Iron supplementation is still required alongside EPO to ensure adequate response.
• Red blood cell transfusion: Reserved for severe, hemodynamically significant anemia (Hb typically <7-8 g/dL) or active, ongoing hemorrhage.

5. Monitoring Response

• Reticulocytosis appears within 3-5 days of starting iron
• Hb rises ~1-2 g/dL per week once adequate iron is supplied
• Serum ferritin confirms store repletion (target ferritin >50 µg/L)