What is Serum Ferritin?
Serum ferritin is a blood protein that reflects the amount of iron stored in your body, primarily in the liver, spleen, and bone marrow, where approximately 1 μg/L of serum ferritin corresponds to about 10 mg of stored iron. 1
Basic Definition and Function
Serum ferritin is a small amount of the iron-storage protein ferritin that circulates in the plasma, while most ferritin remains inside cells 1. Under normal conditions, there is a direct, quantitative relationship between serum ferritin concentration and total body iron stores 1.
Normal reference ranges vary by sex and age:
- Men: average 135 μg/L (or 69 ng/mL in some studies) 1, 2
- Women: average 43 μg/L (or 35 ng/mL) 1, 2
- Children aged 6-24 months: approximately 30 μg/L 1
Clinical Significance
Serum ferritin serves as the most specific indicator of depleted iron stores, particularly when extremely low or extremely high 3. It functions as an early warning system for iron status:
Low Ferritin (Iron Deficiency)
- <15 μg/L: Highly specific for absent iron stores (specificity 99%) 4
- <30 μg/L: Generally indicates low body iron stores 4
- <45 μg/L: Provides optimal balance of sensitivity and specificity for iron deficiency 5, 4
Low ferritin becomes abnormal before exhaustion of mobilizable iron stores and before anemia develops, making it an earlier indicator than hemoglobin or transferrin saturation 6.
High Ferritin (Iron Overload)
- >200 μg/L: Suggests increased iron stores 6
- >1000 μg/L: In hemochromatosis patients, predicts presence of cirrhosis when combined with elevated liver enzymes 7
Critical Limitation: The Acute Phase Reactant Problem
The major caveat is that serum ferritin is an acute phase reactant, meaning it rises during inflammation, infection, or tissue damage independent of actual iron stores 3, 1. This creates a significant clinical challenge:
- Chronic infection, inflammation, hepatitis, cirrhosis, neoplasia, or arthritis can elevate ferritin levels even when iron stores are depleted 1
- In inflammatory conditions, patients may have iron deficiency despite ferritin levels of 100-700 ng/mL 3
- Ferritin >150 μg/L is unlikely to occur with absolute iron deficiency, even with inflammation 4
Cellular Origin
Recent research shows that serum ferritin is actively secreted by macrophages (particularly splenic macrophages) through a nonclassical lysosomal secretory pathway, rather than simply leaking from damaged cells 8. It is composed mostly of L-subunits with low iron content 8.
Clinical Use Algorithm
When interpreting serum ferritin:
- If ferritin is extremely low (<15 μg/L): Iron deficiency is confirmed with near certainty
- If ferritin is 15-45 μg/L: Iron deficiency is likely; consider clinical context
- If ferritin is 45-100 μg/L with inflammation: Iron deficiency remains possible; use additional tests (transferrin saturation, soluble transferrin receptor) 5
- If ferritin is >150 μg/L: Absolute iron deficiency is unlikely even with inflammation 4
Serum ferritin is most accurate as a predictor when it is at the extremes—very low indicating deficiency or very high indicating overload 3. In the middle ranges, clinical judgment and additional testing become essential, particularly when inflammation is present.