What is the recommended approach to diagnose and manage iron‑deficiency anemia, including first‑line oral iron dosing, criteria for intravenous iron, monitoring parameters, and indications for red‑cell transfusion?

Management of Iron Deficiency Anemia

First-Line Oral Iron Treatment

Start ferrous sulfate 200 mg (65 mg elemental iron) once daily immediately upon diagnosis—this is the preferred first-line treatment due to superior cost-effectiveness with equivalent efficacy to all other oral formulations. 1, 2

• Take on an empty stomach for optimal absorption, though taking with food is acceptable if gastrointestinal side effects occur 2
• Once-daily dosing is superior to multiple daily doses—hepcidin remains elevated for 48 hours after iron intake, blocking further absorption and increasing side effects without improving efficacy 1, 2
• Add vitamin C (ascorbic acid) 500 mg with each iron dose to enhance absorption, particularly critical when transferrin saturation is severely low 1, 2
• Avoid tea and coffee within 1 hour of taking iron, as these inhibit absorption 2
• Alternative formulations (ferrous fumarate 106 mg elemental iron or ferrous gluconate 38 mg elemental iron) are equally effective if ferrous sulfate is not tolerated 1, 2

Expected Response and Monitoring

• Hemoglobin should rise by approximately 2 g/dL after 3-4 weeks of treatment 1, 2
• Recheck hemoglobin at 4 weeks; failure to rise by at least 1 g/dL indicates poor adherence, ongoing blood loss, or malabsorption 2, 3
• Continue oral iron for 3 months after hemoglobin normalizes to fully replenish iron stores—total treatment duration is typically 6-7 months 1, 2
• Monitor hemoglobin and red cell indices every 3 months for the first year, then again after another year 1, 2

Indications for Intravenous Iron

Switch to intravenous iron when oral therapy fails or is contraindicated—do not persist with ineffective oral treatment beyond 4 weeks. 1, 2

Absolute Indications

• Active inflammatory bowel disease with hemoglobin <10 g/dL—inflammation-induced hepcidin severely impairs oral iron absorption 1, 2
• Intolerance to at least two different oral iron preparations despite trying ferrous sulfate, ferrous fumarate, and ferrous gluconate 1, 2
• Failure of ferritin levels to improve after 4 weeks of adherent oral therapy 2
• Post-bariatric surgery patients due to disrupted duodenal absorption mechanisms 1, 2

Relative Indications

• Celiac disease with inadequate response to oral iron despite strict gluten-free diet adherence 1, 2
• Ongoing gastrointestinal blood loss exceeding oral replacement capacity 2
• Chronic heart failure with iron deficiency (ferritin <100 ng/mL or 100-300 ng/mL with transferrin saturation <20%)—IV iron improves symptoms and quality of life 1, 2
• Chronic kidney disease with functional iron deficiency (ferritin 100-300 ng/mL with transferrin saturation <20%) 2

Preferred Intravenous Iron Formulations

Choose IV iron preparations that replace iron deficits in 1-2 infusions rather than multiple infusions to minimize risk and improve convenience. 1, 2

• Ferric carboxymaltose: 750-1000 mg per 15-minute infusion; two doses ≥7 days apart provide total 1500 mg 1, 2
• Ferric derisomaltose: 1000 mg as single infusion 2
• Avoid iron dextran as first-line due to higher anaphylaxis risk, though true anaphylaxis with any IV iron is rare (0.6-0.7%) 1, 2
• Most infusion reactions are complement activation-related pseudo-allergies (CARPA), not true anaphylaxis—they respond to slowing the infusion rate 1
• Administer in a setting with resuscitation equipment available 1

Diagnostic Workup

All men and postmenopausal women with confirmed iron deficiency anemia require gastrointestinal investigation to exclude malignancy. 1

• Perform bidirectional endoscopy (upper endoscopy and colonoscopy) unless there is significant non-GI blood loss 1
• Take small bowel biopsies during upper endoscopy, as 2-3% of patients with iron deficiency anemia have celiac disease 1
• Screen for celiac disease with anti-endomysial antibodies and IgA measurement 1, 2
• Test for Helicobacter pylori and eradicate if present in patients with recurrent iron deficiency anemia 1
• In premenopausal women, assess menstrual blood loss first; GI investigation is only indicated if upper GI symptoms, alarm features, or family history of colon cancer are present 1, 2

Special Population Considerations

Inflammatory Bowel Disease

• IV iron is first-line treatment when hemoglobin <10 g/dL with active inflammation—oral iron is poorly absorbed and may worsen inflammation 1, 2
• Treat active intestinal inflammation to enhance iron absorption and reduce iron depletion 1, 2
• For mild anemia (hemoglobin >10 g/dL) with clinically inactive disease, oral iron may be appropriate 2
• IV iron is more effective (odds ratio 1.57 for achieving 2.0 g/dL hemoglobin increase) and better tolerated than oral iron in IBD patients 2

Pregnancy

• Start oral low-dose iron 30 mg/day at first prenatal visit for prevention 2
• Treat anemia with 60-120 mg/day elemental iron 2
• Refer pregnant women with hemoglobin <9.0 g/dL for further medical evaluation 2
• IV iron is safe and effective during second and third trimesters if oral iron fails 1

Post-Bariatric Surgery

• IV iron is preferred due to anatomic disruption of duodenal absorption 1, 2

Celiac Disease

• Ensure strict adherence to gluten-free diet to improve iron absorption 1, 2
• Progress to IV iron if iron stores do not improve despite dietary compliance 1, 2

Red Cell Transfusion Indications

Reserve blood transfusions for severe, symptomatic anemia with circulatory compromise or hemodynamic instability. 2

• Target hemoglobin 70-90 g/dL (80-100 g/dL in unstable coronary artery disease) 2
• One unit of packed red cells supplies only ~200 mg elemental iron; follow restrictive transfusion with adequate iron replacement, preferably IV 2
• Parenteral iron produces clinically meaningful hemoglobin rise within one week, making it the preferred alternative to transfusion in most cases 2

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 beyond 4 weeks without hemoglobin response—reassess for non-adherence, malabsorption, or ongoing blood loss and switch to IV iron 2, 3
• Do not use oral iron in active IBD patients with hemoglobin <10 g/dL—IV iron is the appropriate first-line option 1, 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 1, 2
• Do not defer iron replacement while awaiting investigations unless colonoscopy is imminent, as iron can interfere with visualization 2

Algorithm for Non-Response to Oral Iron

If hemoglobin fails to rise by ≥1 g/dL after 4 weeks of oral iron: 2, 3

1. Verify adherence to oral therapy
2. Evaluate for ongoing blood loss (occult GI bleeding, menorrhagia)
3. Consider malabsorption syndromes (celiac disease, IBD, post-bariatric surgery)
4. Check for concurrent deficiencies (vitamin B12, folate)
5. Assess for systemic disease (chronic inflammation, bone marrow pathology)
6. Switch to intravenous iron if oral therapy failure is confirmed