What level of iron deficiency indicates the need for intravenous (IV) iron infusion versus oral (PO) replacement in patients with iron deficiency anemia?

Iron Deficiency: IV Infusion vs. Oral Replacement Thresholds

Intravenous iron should be used when ferritin is <30 ng/mL (without inflammation) or <100 ng/mL (with inflammation), when transferrin saturation is <20%, when hemoglobin is <10 g/dL, or in patients with chronic inflammatory conditions, malabsorption, oral iron intolerance, or ongoing blood loss. 1, 2

Absolute Iron Deficiency Thresholds

Without inflammation:

• Ferritin <30 ng/mL with transferrin saturation <15-20% indicates absolute iron deficiency requiring IV iron 3, 1, 2
• This threshold applies to otherwise healthy individuals without active inflammatory disease 3, 4

With inflammation or chronic disease:

• Ferritin <100 ng/mL indicates absolute iron deficiency even in the presence of inflammation 3, 1
• This lower threshold accounts for ferritin's elevation as an acute phase reactant during inflammatory states 2
• Transferrin saturation <20% supports the diagnosis when ferritin is between 30-100 ng/mL 1, 5

Clinical Scenarios Mandating IV Iron

Severe anemia:

• Hemoglobin <10 g/dL (100 g/L) warrants first-line IV iron therapy regardless of ferritin level 1, 2, 4
• This threshold reflects the need for rapid correction that oral iron cannot provide 2

Chronic inflammatory conditions:

• Active inflammatory bowel disease patients should receive IV iron as first-line therapy 1, 2
• Chronic kidney disease patients, particularly those on hemodialysis, require IV iron as oral preparations cannot maintain adequate stores 1, 6
• Heart failure patients with iron deficiency benefit from IV iron to improve exercise capacity 4, 5
• Cancer patients with functional iron deficiency (ferritin <800 ng/mL and transferrin saturation <20%) may benefit from IV iron, especially when receiving erythropoiesis-stimulating agents 3, 1

Malabsorption states:

• Celiac disease, atrophic gastritis, and post-bariatric surgery patients require IV iron due to impaired absorption 2, 4
• Oral iron is ineffective when the gastrointestinal tract cannot absorb iron adequately 2

Oral iron failure or intolerance:

• Previous intolerance to oral iron (gastrointestinal side effects occur in ~50% of patients) warrants switching to IV iron 1, 2, 5
• Insufficient increase in iron parameters within 2 weeks of oral therapy indicates need for IV iron 2
• Lack of hemoglobin response after 4 weeks of oral therapy should prompt consideration of IV iron 1

Ongoing blood loss:

• Active bleeding requiring rapid iron repletion necessitates IV iron 2, 4
• Situations where oral iron cannot keep pace with losses (heavy menstrual bleeding, gastrointestinal bleeding) benefit from IV administration 4

Functional Iron Deficiency in Special Populations

Cancer patients:

• Functional iron deficiency defined as ferritin ≤800 ng/mL with transferrin saturation <20% may warrant IV iron, particularly when using erythropoiesis-stimulating agents 3, 1
• The NCCN recommends IV iron for absolute deficiency (ferritin <30 ng/mL, transferrin saturation <15%) but suggests adding ESAs for functional deficiency 3

Pregnancy:

• IV iron is indicated during second and third trimesters when oral iron is insufficient or not tolerated 4
• Up to 84% of pregnant women in the third trimester have iron deficiency 4

Oral Iron as First-Line

Oral iron remains appropriate when:

• Ferritin is 30-100 ng/mL without inflammation and hemoglobin is >10 g/dL 4, 5
• No chronic inflammatory conditions are present 2
• Gastrointestinal absorption is intact 4
• No ongoing significant blood loss exists 2
• Patient can tolerate oral preparations 5

Dosing considerations for oral iron:

• Ferrous sulfate 325 mg daily or every other day improves absorption and reduces side effects 4, 5
• Response should be assessed at 2-4 weeks 1, 5

Critical Pitfalls to Avoid

Do not use IV iron during active infection (though chronic inflammation is not a contraindication) 3, 2

Do not check iron parameters too early after IV infusion as circulating iron interferes with assays; wait 4-8 weeks 2

Do not rely on ferritin alone in inflammatory states as it rises as an acute phase reactant and may mask true iron deficiency 2, 6

Do not use intramuscular iron as it is obsolete with no proven advantage over oral or IV routes 2

Monitor for hypophosphatemia and allergic reactions with high-dose IV iron formulations, though serious reactions are rare (<1% with newer formulations) 7, 5

Monitoring After Treatment

• Reassess hemoglobin and iron parameters 4-8 weeks after IV iron completion 1, 2
• Expected response is 1-2 g/dL hemoglobin increase within 4-8 weeks 2
• Reinitiate treatment when ferritin drops below 100 ng/mL or hemoglobin falls below 12 g/dL (women) or 13 g/dL (men) 1, 2