Management of Iron Deficiency with Normal Hemoglobin
Oral iron supplementation is strongly recommended for patients with a ferritin level of 5 ng/mL despite normal hemoglobin, as this represents true iron deficiency that requires treatment to prevent future anemia and maintain optimal health. 1, 2
Diagnosis and Clinical Significance
- A ferritin level of 5 ng/mL indicates severe iron deficiency, even with normal hemoglobin levels
- Definitive iron deficiency is defined as a ferritin level <15 μg/L (specificity 98%) 1
- Normal hemoglobin with low ferritin represents "iron deficiency without anemia" - a pre-anemic state where iron stores are depleted but have not yet affected hemoglobin production
- This condition can still cause significant symptoms including fatigue, reduced exercise tolerance, and cognitive effects
Treatment Algorithm
First-line Treatment:
- Oral iron supplementation:
Monitoring:
- Check ferritin levels after 4-8 weeks of therapy
- Continue treatment until ferritin reaches target level of 50-100 ng/mL 1
- Monitor hemoglobin to ensure it remains in normal range
Duration of Treatment:
- Continue iron therapy for 3-6 months after normalization of ferritin to replenish iron stores
- Consider maintenance therapy if underlying cause cannot be corrected
Evaluation of Underlying Causes
Investigate potential causes of iron deficiency:
- Blood loss (menstrual, gastrointestinal)
- Malabsorption (celiac disease, H. pylori infection)
- Dietary insufficiency
- Increased requirements (pregnancy, adolescence)
Special Considerations
- Avoid excessive iron supplementation as high ferritin levels (>300 μg/L) may increase risk of adverse events 1, 5
- Patients with inflammatory conditions may have falsely elevated ferritin; in these cases, ferritin up to 100 μg/L may still represent iron deficiency 1, 2
- For women with heavy menstrual bleeding (a common cause of iron deficiency), consider tranexamic acid during menstruation in addition to iron therapy 6
Pitfalls to Avoid
- Ignoring iron deficiency when hemoglobin is normal - Iron deficiency without anemia still requires treatment
- Using outdated ferritin cutoffs - Traditional laboratory lower limits (often 10-15 ng/mL) are too low; evidence supports using higher cutoffs (30 μg/L) for diagnosing iron deficiency 7
- Inadequate treatment duration - Iron stores must be fully replenished, not just normalized
- Missing underlying causes - Always investigate why iron deficiency developed
Iron deficiency, even without anemia, represents a clinically significant condition that requires proper treatment to prevent progression to anemia and to address symptoms that may already be present despite normal hemoglobin levels.