What does low ferritin and normal iron saturation imply for iron deficiency anemia diagnosis and treatment?

Iron Saturation 52% with Ferritin 14 μg/L: Absolute Iron Deficiency

This combination definitively indicates absolute iron deficiency with depleted iron stores, despite the seemingly "normal" transferrin saturation, and requires immediate iron supplementation. 1, 2

Understanding This Paradoxical Pattern

The ferritin of 14 μg/L is the critical diagnostic finding here:

• Ferritin <15 μg/L has 99% specificity for absolute iron deficiency and confirms the diagnosis definitively, regardless of other iron parameters 1
• This ferritin level indicates severely depleted or absent iron stores in the bone marrow, liver, and spleen 3
• The transferrin saturation of 52% appears falsely reassuring but does not exclude iron deficiency 3

Why the Transferrin Saturation is Misleading

The elevated transferrin saturation (52%) in the context of very low ferritin represents a measurement artifact or transient state:

• Transferrin saturation reflects only the iron immediately available in circulation for erythropoiesis, not total body iron stores 3
• Day-to-day variation in serum iron and transferrin saturation is substantial, making single measurements unreliable 3
• Serum iron concentration can be temporarily elevated by recent dietary intake, diurnal variation, or hemolysis during blood draw 3
• Ferritin is the most specific indicator of depleted iron stores, especially when extremely low 3

Clinical Interpretation Algorithm

When ferritin and transferrin saturation appear discordant:

1. Ferritin <15 μg/L always takes diagnostic priority - this confirms absolute iron deficiency regardless of transferrin saturation 1, 2
2. Check inflammatory markers (CRP, ESR) to rule out acute phase reaction masking even lower true ferritin 3
3. In the absence of inflammation, ferritin <15 μg/L is diagnostic and no additional testing is needed 3, 1

Immediate Management

Iron supplementation must be initiated immediately:

• Oral iron 30-60 mg elemental iron daily (or 60 mg every other day for better absorption and fewer side effects) is first-line therapy 1, 2, 4
• Reassess hemoglobin in 2-4 weeks; expect at least 1-2 g/dL increase if responding appropriately 2, 5
• If no response or intolerance to oral iron, switch to intravenous iron 1, 4

Investigate the Underlying Cause

Ferritin this low demands investigation for the source of iron loss:

• In men and postmenopausal women: bidirectional endoscopy is mandatory to exclude gastrointestinal bleeding or malignancy 2, 4, 6
• In premenopausal women: evaluate for heavy menstrual bleeding, but still consider GI evaluation if no obvious gynecologic cause 2, 4
• Test for Helicobacter pylori infection and celiac disease, both common causes of iron deficiency 2, 4
• Recurrent blood loss accounts for 94% of iron deficiency cases 2

Critical Pitfall to Avoid

Do not be falsely reassured by the "normal" transferrin saturation of 52%. The ferritin of 14 μg/L is unequivocal evidence of depleted iron stores and requires treatment. 3, 1, 2 Waiting for transferrin saturation to drop before treating would allow continued iron depletion and potential progression to symptomatic anemia. 3, 4