What does serum ferritin indicate?

Serum Ferritin as an Indicator of Iron Status

Serum ferritin is primarily an indicator of iron stores in the body, with low levels (<30 μg/L) indicating iron deficiency and elevated levels suggesting possible iron overload (>300 μg/L in men, >200 μg/L in women), though it is also an acute phase reactant that increases with inflammation, infection, and cellular damage regardless of iron status. 1

Interpretation of Ferritin Levels

Ferritin levels can be interpreted as follows:

• <30 μg/L: Iron deficiency in the absence of inflammation 1
• 30-100 μg/L: Possible iron deficiency or anemia of chronic disease if inflammation is present 1
• >100 μg/L: Anemia of chronic disease or iron overload 1
• >1000 μg/L: Requires further investigation as this may indicate malignancy, especially in tertiary care settings 1

Clinical Significance

Iron Deficiency

• Serum ferritin is highly specific (92-98%) for iron deficiency at low levels 1, 2
• At a threshold of 30 μg/L, ferritin demonstrates approximately 79% sensitivity and 98% specificity for iron deficiency in clinical populations 2
• Values below 10 ng/ml are typically associated with iron-deficient erythropoiesis 3

Iron Overload

• Thresholds for suspecting iron overload: >300 μg/L in men and >200 μg/L in women 1
• Ferritin levels are used to monitor iron overload treatment, with target levels of 50-100 μg/L during therapeutic phlebotomy 1
• For patients on iron chelation therapy (e.g., deferasirox), target ferritin levels are 500-1000 μg/L 1, 4

Confounding Factors

Inflammation and Acute Phase Response

• Ferritin increases during inflammation regardless of iron status 1, 5, 6
• It should be interpreted alongside inflammatory markers (CRP, ESR) 1
• Serum ferritin may reflect cellular damage, as it can be a leakage product from damaged cells 6

Special Populations

• Chronic Kidney Disease: Ferritin may not accurately reflect iron stores; additional tests like transferrin saturation should be considered 1
• Liver Disease: Can cause elevated ferritin independent of iron status 1
• Malignancy: Often associated with markedly elevated ferritin (>1000 μg/L) 1
• Metabolic Syndrome: May elevate ferritin independent of iron status 1, 5

Diagnostic Approach

When interpreting serum ferritin:

1. Measure simultaneously with transferrin saturation (TSAT) for more accurate assessment of iron status 1

2. Consider concurrent evaluation of:

   • Inflammatory markers (CRP, ESR)
   • Liver function tests
   • Complete blood count
   • Metabolic panel
   • Viral hepatitis serologies when appropriate 1

3. For suspected iron overload with metabolic syndrome:

   • Calculate ferritin/AST ratio (sensitivity 83.3%, specificity 78.6%) 1
   • Consider genetic testing for HFE mutations (C282Y and H63D) 1
   • Consider MRI for non-invasive quantification of liver iron content 1

Clinical Applications

• Monitoring iron chelation therapy: Deferasirox treatment is indicated when serum ferritin is consistently >1000 μg/L in transfusion-dependent patients 4
• Guiding phlebotomy: Weekly phlebotomy may be indicated for iron overload with target ferritin of 50-100 μg/L 1
• Screening: While useful in clinical settings, evidence for ferritin's accuracy in screening asymptomatic populations is limited 2

Remember that a single ferritin measurement should not be used in isolation, particularly in conditions associated with inflammation or cellular damage, as it may not accurately reflect iron stores in these contexts.