What is the next step in management for a patient with previously diagnosed iron deficiency anemia, now with normal hemoglobin, hematocrit, and Total Iron Saturation (TSAT), but persistent fatigue, and a ferritin level of 27?

Management of Persistent Fatigue with Low Ferritin Despite Normal Hemoglobin

Continue iron supplementation for an additional 3 months to fully replenish iron stores, as a ferritin of 27 ng/mL indicates inadequate iron stores despite normalized hemoglobin. 1

Rationale for Continued Iron Therapy

Your patient's ferritin level of 27 ng/mL remains below the threshold needed for adequate iron stores, even though hemoglobin and hematocrit have normalized. The British Society of Gastroenterology guidelines explicitly state that iron supplementation should be continued for three months after correction of anemia to replenish body stores 1. The goal is not just to normalize hemoglobin, but to restore iron stores, which requires ferritin levels substantially higher than 27 ng/mL 1.

Why Fatigue Persists

• Iron deficiency without anemia causes symptoms: Patients with low ferritin but normal hemoglobin commonly experience fatigue, difficulty concentrating, irritability, and exercise intolerance 2
• Tissue iron depletion: A ferritin of 27 ng/mL indicates depleted iron stores that affect cellular function beyond red blood cell production 2
• Inadequate store repletion: The aim of treatment is to restore hemoglobin AND replenish body stores; if this cannot be achieved, further evaluation should be considered 1

Specific Management Steps

Continue Oral Iron Supplementation

• Maintain ferrous sulfate 200 mg twice daily (or equivalent elemental iron 100-200 mg daily) 1, 3
• Duration: Continue for 3 months after anemia correction, which means continuing now since stores are not yet replenished 1
• Alternative dosing: Consider every-other-day dosing if tolerability is an issue, as this improves absorption 3
• Add ascorbic acid: Consider 250-500 mg twice daily with iron to enhance absorption if response has been suboptimal 1

Monitor Response

• Recheck ferritin in 2-4 weeks to ensure upward trend 3
• Target ferritin: While guidelines don't specify an exact target for symptom resolution, recent evidence suggests ferritin <45 ng/mL indicates iron deficiency in non-inflammatory states 3
• Follow-up schedule: Once normalized, monitor hemoglobin and ferritin every 3 months for one year, then annually 1

When to Consider Intravenous Iron

Switch to intravenous iron if: 1

• Intolerance to oral iron after trying at least two different oral preparations
• Poor absorption (history of celiac disease, atrophic gastritis, bariatric surgery)
• Ongoing blood loss that cannot be controlled
• Lack of response to adequate oral iron therapy after 2-4 weeks 3

Available IV formulations include iron sucrose (200 mg over 10 minutes), ferric carboxymaltose (1000 mg over 15 minutes), or iron dextran (requires test dose) 1.

Important Caveats

Do not stop iron prematurely: The most common error is discontinuing iron supplementation once hemoglobin normalizes, leaving stores depleted and symptoms persistent 1, 4. Iron therapy should continue for 6 months total after hemoglobin normalizes to ensure complete store repletion 4.

Reassess if no improvement: If ferritin fails to rise or symptoms persist despite 3 months of adequate iron supplementation with documented compliance, consider 1:

• Ongoing occult blood loss
• Malabsorption (celiac disease, H. pylori, atrophic gastritis)
• Chronic inflammation masking true iron status
• Alternative causes of fatigue unrelated to iron deficiency

Monitor for recurrence: Additional oral iron should be given if hemoglobin or ferritin falls below normal during follow-up monitoring 1.