What are the indications for IV (intravenous) iron supplementation in patients with iron deficiency anemia?

Indications for Intravenous Iron Therapy

Intravenous iron should be used as first-line treatment in patients with active inflammatory bowel disease and hemoglobin <10 g/dL, those with intolerance to at least two different oral iron preparations, post-bariatric surgery patients, chronic kidney disease patients on dialysis, heart failure patients with iron deficiency, and during the second and third trimesters of pregnancy when oral iron fails. 1, 2, 3, 4

Absolute Indications for IV Iron (First-Line Therapy)

Active Inflammatory Conditions with Severe Anemia

• Inflammatory bowel disease with clinically active disease and hemoglobin <10 g/dL requires IV iron as first-line treatment because inflammation-induced hepcidin elevation severely impairs intestinal iron absorption, making oral iron ineffective. 1, 2
• The European Crohn's and Colitis Organisation confirms 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. 1
• Chronic kidney disease patients, particularly those on hemodialysis, should receive IV iron due to functional iron deficiency and inflammation-mediated hepcidin upregulation. 1, 4

Malabsorption States

• Post-bariatric surgery patients require IV iron due to disrupted duodenal absorption mechanisms, particularly after procedures that bypass the duodenum where iron absorption occurs. 2, 5, 4
• Celiac disease patients with inadequate response to oral iron despite strict gluten-free diet adherence should receive IV iron. 2, 5

Heart Failure

• Heart failure patients (NYHA class II/III) with iron deficiency (ferritin <100 ng/mL or ferritin 100-300 ng/mL with transferrin saturation <20%) should receive IV iron to improve exercise capacity and quality of life. 2, 3, 4

Pregnancy

• IV iron is indicated during the second and third trimesters when oral iron fails or is not tolerated, as rapid correction is often needed. 2, 4

Relative Indications for IV Iron (After Oral Iron Failure)

Oral Iron Intolerance

• Intolerance to at least two different oral iron preparations (ferrous sulfate, ferrous gluconate, and ferrous fumarate) is an indication to switch to IV iron. 2, 5, 6
• Common intolerable side effects include nausea, constipation, diarrhea, and dyspepsia that prevent adherence. 5, 6

Inadequate Response to Oral Iron

• Failure of ferritin levels to improve after 4 weeks of compliant oral therapy indicates need for IV iron. 2, 5
• Hemoglobin failing to rise by approximately 2 g/dL after 3-4 weeks of oral iron suggests inadequate response. 2, 7

Ongoing Blood Loss

• Ongoing gastrointestinal blood loss exceeding oral replacement capacity requires IV iron. 2, 5
• Portal hypertensive gastropathy with ongoing bleeding unresponsive to oral therapy should be treated with IV iron. 5

Cancer Patients

• Cancer patients with iron deficiency anemia who have unsatisfactory response to oral iron or cannot tolerate it should receive IV iron, particularly those receiving chemotherapy. 8, 4

Preferred IV Iron Formulations

• Choose IV iron preparations that replace iron deficits in 1-2 infusions rather than multiple infusions to minimize risk and improve patient convenience. 2, 5
• Ferric carboxymaltose (500-1000 mg single doses delivered within 15 minutes) is a preferred formulation. 2, 3
• The FDA has approved ferric carboxymaltose (Injectafer) for iron deficiency anemia in adults and pediatric patients ≥1 year with intolerance or unsatisfactory response to oral iron, non-dialysis dependent CKD, and iron deficiency in heart failure. 3

Safety Considerations

• All IV iron formulations have similar overall safety profiles, with true anaphylaxis being very rare (0.6-0.7%). 2, 5, 9
• Most reactions are complement activation-related pseudo-allergy (infusion reactions) rather than true anaphylaxis, and respond to slowing the infusion rate. 2, 5
• Resuscitation facilities must be available when administering any IV iron formulation. 1
• Do not use IV iron during active infection, as iron supplementation may promote bacterial growth and inflammation. 5

Common Pitfalls to Avoid

• Do not prescribe oral iron to patients with active IBD and hemoglobin <10 g/dL—this is ineffective and potentially harmful due to inflammation-induced hepcidin blocking absorption. 1, 2
• Do not continue oral iron indefinitely without response—reassess after 4 weeks and switch to IV iron if hemoglobin fails to rise. 2, 7
• Do not confuse infusion reactions with anaphylaxis—treat complement activation reactions appropriately rather than discontinuing all IV iron. 5, 9
• Do not delay IV iron in malabsorption states, as patients with celiac disease, post-bariatric surgery, or active IBD inflammation will not respond adequately to oral iron. 5, 4