What is the recommended treatment for a patient with iron deficiency anemia, indicated by a ferritin level of 21.2, and is intravenous (IV) iron supplementation a suitable option?

Treatment Recommendation for Ferritin 21.2

Start with oral iron supplementation (ferrous sulfate 200 mg three times daily or alternate-day dosing) as first-line therapy, and reserve intravenous iron for specific indications including intolerance to oral iron, malabsorption, ongoing blood loss, or certain chronic conditions. 1

Initial Assessment and Context

A ferritin of 21.2 ng/mL indicates absolute iron deficiency requiring treatment, though the specific approach depends on clinical context:

• If ferritin <30 ng/mL without inflammation: This confirms iron deficiency 2
• If ferritin <45 ng/mL or 46-99 ng/mL with transferrin saturation <20%: Diagnostic of iron deficiency in patients without inflammation 3
• Investigate underlying cause: In men and postmenopausal women, bidirectional endoscopy is indicated; in younger women with plausible causes (heavy menstrual bleeding), treat the bleeding source 3

Oral Iron: First-Line Therapy

Oral iron is the preferred initial treatment for most patients because it is simple, cheap, and effective 1:

• Standard dosing: Ferrous sulfate 200 mg three times daily 1
• Alternative formulations: Ferrous gluconate or ferrous fumarate are equally effective 1
• Alternate-day dosing: Improves absorption and may reduce side effects 3, 2
• Ascorbic acid: Enhances absorption and should be considered when response is poor 1
• Expected response: Hemoglobin should rise by 2 g/dL after 3-4 weeks 1
• Duration: Continue for 3 months after correction of anemia to replenish iron stores 1

Common pitfall: Approximately 50% of patients have decreased adherence due to gastrointestinal adverse effects 3. Consider alternate-day dosing or liquid preparations when tablets are not tolerated 1.

Intravenous Iron: Specific Indications

IV iron should be reserved for specific clinical scenarios, not routinely used for a ferritin of 21.2 1:

Clear Indications for IV Iron:

• Intolerance to at least two oral iron preparations 1, 4
• Non-compliance with oral therapy 1
• Malabsorption (celiac disease, post-bariatric surgery, inflammatory bowel disease) 3, 2
• Ongoing blood loss that cannot be controlled 2
• Chronic kidney disease (non-dialysis dependent) 4
• Heart failure with iron deficiency to improve exercise capacity 4, 2
• Second and third trimesters of pregnancy 2
• Inadequate response to oral iron after 2-4 weeks 3

IV Iron Formulations and Dosing:

When IV iron is indicated 4:

• For patients ≥50 kg: 750 mg IV in two doses separated by at least 7 days (total 1,500 mg per course)
• For patients <50 kg: 15 mg/kg body weight IV in two doses separated by at least 7 days
• Alternative: Single dose of 15 mg/kg up to maximum 1,000 mg in adults

Important Safety Considerations for IV Iron:

• Hypersensitivity reactions: Rare with newer formulations (<1%) but require monitoring 3, 2
• Hypophosphatemia: Check serum phosphate in patients requiring repeat courses within 3 months 4
• Avoid extravasation: Can cause long-lasting brown discoloration 4
• No test dose required for most modern formulations (except low molecular weight iron dextran) 1

Clinical Decision Algorithm

For your patient with ferritin 21.2:

1. Identify and treat underlying cause (blood loss, malabsorption, dietary deficiency) 1, 3
2. Start oral iron (ferrous sulfate 200 mg daily or alternate days) 1, 3
3. Reassess in 2-4 weeks: Check hemoglobin response 3
4. If inadequate response or intolerance: Switch to IV iron 1, 3
5. Continue treatment for 3 months after anemia correction to replenish stores 1

Failure to respond to oral iron is usually due to poor compliance, misdiagnosis, continued blood loss, or malabsorption 1. In a study of oral iron non-responders, only 21% responded to continued oral therapy versus 65% who responded to IV iron 1.

Special Populations

Heart failure patients: Even without anemia, IV iron improves exercise capacity when ferritin <100 ng/mL or ferritin 100-300 ng/mL with transferrin saturation <20% 1, 4

Chronic kidney disease: Higher ferritin targets (>200 ng/mL) may be appropriate, and IV iron is often preferred 1

Inflammatory conditions: Oral iron absorption is impaired due to hepcidin upregulation; IV iron is more effective 1, 2