What is ferritin and what does it measure?

What is Ferritin and What Does It Measure?

Serum ferritin is a blood protein that serves as the primary surrogate marker for total body iron stores, with each 1 μg/L of serum ferritin corresponding to approximately 10 mg of stored iron. 1

Primary Function

Ferritin measures intracellular iron stores in both the reticuloendothelial system (RES) and parenchymal tissues, making it the mainstay for assessing total body iron status in both adults and children. 2 No other currently available marker can substitute for serum ferritin in terms of assessing tissue iron stores. 2

Clinical Interpretation

Normal Reference Values

• Men: Average 135 μg/L 1
• Women: Average 43 μg/L 1
• Children (6-24 months): Approximately 30 μg/L 1

Diagnostic Thresholds for Iron Deficiency

• Traditional cutoff: ≤15 μg/L (75% sensitivity, 98% specificity for absolute iron deficiency) 1
• Low ferritin levels are highly specific for iron deficiency 2
• Ferritin is the earliest indicator of depleted iron stores, detecting deficiency before anemia develops 1, 3

Critical Limitation: The Acute Phase Reactant Problem

The major caveat is that ferritin behaves as an acute-phase reactant, meaning inflammation, infection, or tissue damage can elevate ferritin levels independent of actual iron status. 2, 1, 3 This creates a significant clinical pitfall:

• A "normal" ferritin level in the presence of inflammation may mask true iron deficiency 1, 3
• In patients with inflammation, infection, or malignancy, iron deficiency may be present even with ferritin levels up to 50-100 μg/L 1
• Ferritin lacks sensitivity for iron deficiency in inflammatory conditions 2

Mechanism of Inflammation Effect

During inflammation, increased hepcidin levels cause an iron shift from circulation and parenchymal cells to the RES, which is reflected by:

• Increased ferritin levels (despite possible iron deficiency) 2
• Decreased transferrin saturation 2

Recommended Clinical Approach

Ferritin should never be interpreted in isolation. 1, 3 The combined assessment of ferritin with other iron parameters is essential:

Complementary Tests

• Transferrin saturation (TSAT): Provides insight into circulating iron available for erythropoiesis; TSAT <20% suggests iron deficiency 2, 1
• Complete blood count: Detects late-stage iron deficiency (anemia) with increased RDW and decreased MCV/MCH 2
• Inflammatory markers (CRP, ESR): Rule out inflammation that might falsely elevate ferritin 1

Combined Interpretation Strategy

The combined assessment and interpretation of ferritin and TSAT is useful in diagnosing both absolute and functional iron deficiency. 2 Additionally, combining these two parameters provides insight into potential toxicity of elevated ferritin levels, since parenchymal iron loading (indicated by high TSAT) is more toxic than RES iron overload. 2

Special Populations

Chronic Kidney Disease Patients

• In hemodialysis patients, ferritin interpretation in isolation is difficult because it acts as an acute-phase reactant and is often elevated irrespective of tissue iron stores 2
• Transferrin saturation may be a more reliable marker in CKD patients, as it is less affected by inflammation 2
• Ferritin levels <25 ng/mL in males and <11 ng/mL in females predict insufficient iron stores for effective erythropoiesis in non-dialysis CKD patients 2

Pediatric Considerations

Serum ferritin is the mainstay for assessment of total body iron stores in children, with the same acute-phase reactant limitations as in adults. 2

Key Clinical Pitfalls to Avoid

1. Never rely on ferritin alone when inflammation is present or suspected 1, 3
2. Do not dismiss iron deficiency based on "normal" ferritin in patients with known inflammatory conditions 1, 3
3. Always assess for gastrointestinal bleeding when iron deficiency is found in patients without obvious blood loss 2
4. Monitor ferritin monthly in patients receiving iron chelation therapy to avoid overchelation 4