What is the treatment for hypoferritinemia with a ferritin level below 15 ng/mL?

Treatment of Hypoferritinemia with Ferritin Below 15 ng/mL

All patients with ferritin below 15 ng/mL should receive iron supplementation to correct iron deficiency and replenish body stores, with oral iron as first-line therapy (ferrous sulfate 200 mg three times daily) and continuation for three months after correction of anemia. 1

Diagnostic Confirmation

A ferritin level below 15 ng/mL indicates absolute iron deficiency in the absence of inflammation 1. However, the 2020 AGA guidelines recommend using a higher diagnostic threshold of 45 ng/mL rather than 15 ng/mL, as this provides superior sensitivity (85% vs 59%) while maintaining acceptable specificity (92% vs 99%) 1. This higher threshold reduces missed diagnoses at the cost of some additional evaluations.

Key diagnostic considerations:

• Check inflammatory markers (CRP, ESR) to exclude false-normal ferritin from acute phase reaction 1
• In patients with inflammation, ferritin <100 ng/mL combined with transferrin saturation <16% suggests iron deficiency 1
• Transferrin saturation <16% is a sensitive marker of iron deficiency, though specificity is only 40-50% 1

Treatment Algorithm

First-Line: Oral Iron Supplementation

Initiate oral iron therapy immediately 1:

• Ferrous sulfate 200 mg three times daily (most cost-effective option) 1
• Alternative preparations: ferrous gluconate or ferrous fumarate are equally effective 1
• Liquid preparations may be tolerated when tablets are not 1
• Add ascorbic acid to enhance iron absorption if response is poor 1

Duration of therapy:

• Continue until hemoglobin normalizes, then continue for an additional 3 months to replenish iron stores 1
• Expected hemoglobin rise: 2 g/dL after 3-4 weeks 1

When to Consider Intravenous Iron

Switch to parenteral iron if 1, 2, 3:

• Intolerance to at least two oral preparations
• Non-compliance with oral therapy
• Malabsorption disorders
• Urgent need for rapid iron repletion
• Transfusion-dependent anemia 1

Important caveat: Parenteral iron is painful (intramuscular), expensive, carries risk of anaphylactic reactions, and provides no faster hemoglobin rise than oral preparations 1. For chronic kidney disease patients on hemodialysis, intravenous iron is often necessary as most cannot maintain adequate iron stores with oral supplementation alone 1.

Monitoring and Follow-Up

Initial response assessment 1, 2:

• Recheck hemoglobin after 3-4 weeks (should increase by 2 g/dL) 1
• Repeat complete iron studies after 8-10 weeks 2

Failure to respond indicates 1:

• Poor compliance (most common)
• Misdiagnosis
• Continued blood loss
• Malabsorption

Long-term monitoring 1:

• Once normalized, monitor hemoglobin and MCV every 3 months for 1 year, then annually 1
• Resume oral iron if hemoglobin or MCV falls below normal 1
• For patients with recurrent deficiency, consider intermittent oral supplementation and monitoring every 6-12 months 2

Evaluation for Underlying Causes

Concurrent with iron supplementation, investigate the source of iron loss 1:

For postmenopausal women and men: Bidirectional endoscopy (EGD and colonoscopy) is strongly recommended to exclude gastrointestinal malignancy 1

For premenopausal women: Consider bidirectional endoscopy conditionally, as menstrual loss is often responsible 1. Women >45 years should be investigated according to standard guidelines 1

Additional testing to consider 1:

• Non-invasive H. pylori testing (treat if positive) 1
• Celiac disease serology first, then small bowel biopsy only if positive 1
• Exclude dietary deficiency, frequent blood donation, or NSAID use 1

Critical Pitfalls to Avoid

• Do not rely on ferritin alone in inflammatory conditions - it is an acute phase reactant and may be falsely elevated despite true iron deficiency 1
• Do not use faecal occult blood testing - it is insensitive and non-specific 1
• Do not administer preventative iron to patients with normal stores - it is inefficient, has side effects, and may be harmful 2
• Do not continue long-term daily iron supplementation once ferritin normalizes - this is potentially harmful 2
• Do not skip the evaluation for underlying causes - treating iron deficiency without addressing the source of loss leads to recurrence 1