When should iron supplements be administered to patients with iron deficiency anemia?

When to Administer Iron to Patients with Iron Deficiency Anemia

Iron supplementation is recommended immediately upon diagnosis of iron deficiency anemia (IDA), defined as low hemoglobin with ferritin <30 μg/L (or <100 μg/L in the presence of inflammation), regardless of whether the underlying cause has been fully identified. 1

Diagnostic Criteria for Iron Supplementation

Iron Deficiency Anemia (IDA)

• Ferritin <30 μg/L with anemia warrants immediate iron supplementation 1
• In the presence of inflammation (elevated CRP), ferritin <100 μg/L with transferrin saturation <20% indicates IDA requiring treatment 1
• Ferritin 30-100 μg/L with transferrin saturation <20% suggests combined iron deficiency and anemia of chronic disease—treat with iron 1

Iron Deficiency Without Anemia

• The decision to supplement iron in patients without anemia is more controversial and depends on symptoms (chronic fatigue, exercise intolerance) and individual patient preferences 1
• Evidence supports treating iron deficiency without anemia in conditions like chronic heart failure, but evidence is limited in other contexts 1

First-Line Treatment Approach

Start oral ferrous sulfate 200 mg once daily immediately upon diagnosis—do not delay treatment while awaiting diagnostic workup. 1, 2

Optimal Oral Iron Regimen

• Ferrous sulfate 200 mg (65 mg elemental iron) once daily is the preferred first-line treatment due to effectiveness and low cost 1, 2
• Once-daily dosing is superior to multiple daily doses—it improves tolerance while maintaining equal or better absorption due to hepcidin regulation 2, 3
• Add vitamin C (ascorbic acid) 500 mg with each iron dose to enhance absorption, especially critical when transferrin saturation is severely low 1, 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

Alternative Dosing for Tolerability

• Every-other-day dosing of 120 mg elemental iron may improve absorption and reduce side effects compared to daily dosing in iron-deficient women 3
• If side effects occur with daily dosing, switch to alternate-day dosing with double the daily dose 3, 4

Expected Response and Monitoring

• Check hemoglobin at 4 weeks—expect a rise of approximately 2 g/dL 1, 2
• Failure to rise by 2 g/dL indicates poor compliance, continued blood loss, malabsorption, or misdiagnosis 1
• Continue oral iron for 3 months after hemoglobin normalizes to fully replenish iron stores 1, 2, 5
• Monitor hemoglobin and red cell indices every 3 months for the first year, then again after another year 1, 2

When to Switch to Intravenous Iron

Intravenous iron should be considered as first-line treatment in specific clinical scenarios: 1

Absolute Indications for IV Iron

• Active inflammatory bowel disease with hemoglobin <10 g/dL—IV iron is first-line treatment 1, 2
• Post-bariatric surgery patients due to disrupted duodenal iron absorption 1, 2
• Intolerance to at least two different oral iron preparations 1
• Failure of ferritin levels to improve after 4 weeks of compliant oral therapy 2
• Ongoing gastrointestinal blood loss exceeding oral replacement capacity 1, 2

Relative Indications for IV Iron

• Celiac disease with inadequate response to oral iron despite gluten-free diet adherence 1, 2
• Chronic kidney disease with functional iron deficiency (ferritin 100-300 ng/mL with transferrin saturation <20%) 2
• Chronic heart failure with iron deficiency (ferritin <100 ng/mL or 100-300 ng/mL with transferrin saturation <20%) to improve exercise capacity and quality of life 2, 6
• Severe anemia requiring rapid hemoglobin increase 4

Preferred IV Iron Formulations

• Choose IV iron preparations that replace iron deficits in 1-2 infusions rather than multiple infusions to minimize risk 1, 2
• Ferric carboxymaltose 500-1000 mg can be delivered over 15 minutes as a single dose 1
• Iron dextran can be given as total dose infusion but carries higher risk of anaphylaxis 1
• True anaphylaxis with modern IV iron formulations is very rare (<1:250,000 administrations) 1, 6

Special Population Considerations

Premenopausal Women

• In women <45 years without upper GI symptoms, assess menstrual blood loss first—menorrhagia, pregnancy, and breastfeeding account for iron deficiency in 5-10% of menstruating women 1, 2
• Screen for celiac disease with antiendomysial antibody and IgA measurement before pursuing endoscopy 1
• Gastrointestinal endoscopy is only indicated if upper GI symptoms are present or age >45 years 1, 2

Inflammatory Bowel Disease

• Treat active inflammation first to enhance iron absorption and reduce iron depletion 1, 2
• Use IV iron as first-line when hemoglobin <10 g/dL with active inflammation 1, 2
• IV iron is more effective than oral iron in IBD patients (odds ratio 1.57 for achieving 2.0 g/dL hemoglobin increase) 2

Pregnant Women

• Start oral low-dose iron 30 mg/day at first prenatal visit for prevention 1, 2
• Treat anemia with 60-120 mg/day elemental iron 1, 2
• Refer pregnant women with hemoglobin <9.0 g/dL for further medical evaluation 1, 2

Cancer and Chemotherapy-Induced Anemia

• Iron supplementation can improve response to erythropoiesis-stimulating agents (ESAs) 1
• Intravenous iron is superior to oral iron when used with ESAs in chemotherapy-induced anemia 1

Critically Ill Patients

• In anemic critically ill patients with iron deficiency confirmed by low hepcidin levels, administer 1 g of IV iron as a single dose using carbohydrate-bound formulations 1
• This approach is associated with reduced length of hospital stay and 90-day mortality 1

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 2, 3
• Do not stop iron therapy when hemoglobin normalizes—continue for 3 months to replenish stores 1, 2, 5
• Do not continue oral iron indefinitely without response—reassess after 4 weeks and switch to IV iron if hemoglobin fails to rise by 2 g/dL 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 while supplementing iron 1, 2
• Do not use parenteral iron as first-line unless specific contraindications to oral therapy exist 1

Failure to Respond to Treatment

If anemia does not resolve within 6 months despite appropriate iron therapy: 1

• Reassess for ongoing blood loss 1, 2
• Evaluate for malabsorption syndromes (celiac disease, atrophic gastritis, H. pylori infection) 1, 7
• Verify patient adherence to therapy 1
• Consider further gastrointestinal investigation if not already completed 1, 7
• Consult hematology for complex cases 1