When is iron replacement recommended?

When to Replace Iron

Iron replacement should be initiated when iron deficiency is diagnosed, defined as ferritin <30-45 ng/mL in patients without inflammation, or when iron deficiency anemia is present (low hemoglobin with confirmed iron deficiency). 1

Diagnostic Thresholds for Iron Replacement

In Patients Without Inflammation

• Ferritin <45 ng/mL is the recommended diagnostic threshold for iron deficiency in anemic patients 1
• For non-anemic iron deficiency, ferritin <30 ng/mL warrants treatment in symptomatic patients or those at risk 2, 3
• In children 6-12 years: ferritin <15 µg/L 2
• In adolescents 12-15 years: ferritin <20 µg/L 2

In Patients With Inflammation or Chronic Disease

The ferritin threshold must be adjusted upward because inflammation falsely elevates ferritin 1:

• Ferritin <100 ng/mL with transferrin saturation <20% indicates iron deficiency in inflammatory conditions 1
• In IBD patients with active disease: ferritin up to 100 µg/L may still represent iron deficiency 1
• In chronic kidney disease: similar thresholds apply 1

Critical caveat: Always measure C-reactive protein alongside ferritin to avoid missing iron deficiency masked by inflammation 2, 3

Specific Clinical Scenarios Requiring Iron Replacement

Iron Deficiency Anemia (All Causes)

• All patients with confirmed iron deficiency anemia should receive iron replacement 1
• Goal: correct anemia AND normalize iron stores 1

Inflammatory Bowel Disease

• Treat when iron deficiency anemia is present (strong recommendation) 1
• Monitor every 3 months during active disease 1
• Monitor every 6-12 months in remission 1
• Re-treat when ferritin drops below 100 µg/L or hemoglobin falls below 12-13 g/dL (gender-dependent) 1

Chronic Kidney Disease

• Screen all adults regardless of symptoms 1
• Screen children with recurrent bleeding and/or anemia symptoms 1
• Replace iron when deficiency is confirmed by low ferritin or transferrin saturation 1

Heart Failure

• Iron replacement improves outcomes in heart failure patients with iron deficiency, even without anemia 1, 3
• Treat when ferritin <100 ng/mL or ferritin 100-300 ng/mL with transferrin saturation <20% 3

Pregnancy

• Iron deficiency affects up to 84% of pregnant women in third trimester 3
• Intravenous iron is preferred during second and third trimesters for rapid repletion 1, 3

Non-Anemic Iron Deficiency

• Treat symptomatic patients with fatigue, restless legs syndrome (affects 32-40%), pica (40-50%), exercise intolerance, or cognitive symptoms 1, 2, 3
• Consider treatment in high-risk populations: adolescents, menstruating women, athletes, vegetarians/vegans, eating disorders 2

Gastrointestinal Bleeding

• Postmenopausal women and men with iron deficiency anemia: bidirectional endoscopy is strongly recommended to identify source 1
• Premenopausal women: consider endoscopy if no other clear cause 1
• Replace iron while investigating underlying cause 1

Route of Administration Decision Algorithm

Start with Oral Iron When:

• Mild anemia (hemoglobin 11.0-11.9 g/dL in women, 11.0-12.9 g/dL in men) 1
• Clinically inactive disease 1
• No previous intolerance to oral iron 1
• No malabsorption conditions 1
• Dose: 35-65 mg elemental iron daily, or alternate-day dosing for better absorption and fewer side effects 1, 2, 4

Use Intravenous Iron as First-Line When:

• Clinically active IBD 1
• Hemoglobin <100 g/L (10 g/dL) 1
• Previous intolerance to oral iron 1
• Malabsorption conditions (celiac disease, post-bariatric surgery, atrophic gastritis) 1, 3
• Chronic kidney disease on dialysis 1, 5, 6
• Heart failure with iron deficiency 1, 3
• Need for rapid iron repletion (pre-surgery, severe anemia) 1
• Second and third trimester pregnancy 1, 3
• Ongoing blood loss despite oral therapy 1
• Need for erythropoiesis-stimulating agents 1

Intravenous dosing: 1 gram total dose as single infusion using modern carbohydrate formulations (ferric carboxymaltose, iron isomaltoside) over 15 minutes to 4 hours depending on formulation 1

Monitoring Treatment Response

• Reassess at 8-10 weeks after starting oral iron 1, 2
• Do not check ferritin earlier than 8 weeks after IV iron (falsely elevated) 1
• Adequate response: hemoglobin rise ≥1.0 g/dL, normalization of ferritin and transferrin saturation 1
• If inadequate response to oral iron after 1 month, switch to IV iron 1

When NOT to Replace Iron

Do not administer iron when ferritin is normal or elevated (>300-400 ng/mL in most contexts) without confirmed deficiency 1, 2. Iron supplementation with normal stores is inefficient, causes side effects, and may be harmful 2. The exception is functional iron deficiency in inflammatory conditions where higher ferritin thresholds apply 1.