How do you interpret a serum ferritin result in a patient with suspected iron deficiency anemia or iron overload?

How to Interpret Serum Ferritin Results

Serum ferritin interpretation requires simultaneous evaluation of transferrin saturation (TS), inflammatory markers (CRP/ESR), and clinical context—never interpret ferritin in isolation. 1

Step 1: Establish the Clinical Context

Before interpreting the ferritin value, determine if inflammation is present by checking CRP or ESR, as ferritin is an acute-phase reactant that rises independently of iron status during inflammation, infection, liver disease, or malignancy. 1, 2 This elevation can mask depleted iron stores even when ferritin appears normal or elevated. 2, 3

Step 2: Calculate Transferrin Saturation

Always calculate TS using the formula: (serum iron × 100) ÷ total iron-binding capacity (TIBC). 2 TS reflects iron readily available for erythropoiesis and is essential for distinguishing between different types of iron disorders. 2

Step 3: Apply Diagnostic Thresholds Based on Clinical Scenario

For Iron Deficiency (Without Inflammation)

• Ferritin <15 μg/L: Absolute iron deficiency confirmed with 99% specificity—no additional testing needed for diagnosis. 1, 2
• Ferritin 15-30 μg/L: Low body iron stores; treatment generally warranted. 2
• Ferritin <45 μg/L: Optimal sensitivity-specificity balance (92% specificity) for clinical decision-making, particularly when evaluating need for GI investigation in iron deficiency anemia. 1, 2
• TS <16-20%: Confirms iron deficiency (absolute or functional). 2

For Iron Deficiency in Inflammatory Conditions

When CRP/ESR are elevated or in patients with chronic kidney disease, inflammatory bowel disease, heart failure, or malignancy, thresholds shift upward: 2

• Ferritin <30 μg/L: Indicates absolute iron deficiency despite inflammation. 2
• Ferritin <100 μg/L with TS <20%: Defines absolute iron deficiency in chronic kidney disease patients. 2
• Ferritin 30-100 μg/L with elevated CRP/ESR: Mixed picture of true iron deficiency plus anemia of chronic disease. 2
• Ferritin >100 μg/L with TS <20% and elevated CRP/ESR: Anemia of chronic disease (inflammatory iron block) where iron is sequestered in reticuloendothelial system. 2

For Iron Overload (Hemochromatosis Screening)

• TS ≥45%: Triggers need for HFE genotyping in suspected hemochromatosis. 1
• Ferritin >250 μg/L (men) or >200 μg/L (women) with elevated TS: Positive in 77% and 56% of C282Y homozygotes, respectively. 1
• Ferritin >1000 μg/L: Accurate predictor for presence of cirrhosis in hemochromatosis; requires liver biopsy for hepatic iron concentration and histopathology. 1
• Ferritin >1000 μg/L with elevated ALT/AST and platelets <200: Predicts cirrhosis in 80% of C282Y homozygotes. 1

Step 4: Recognize Common Diagnostic Patterns

Pattern 1: Low Ferritin + Low TS

Absolute iron deficiency—depleted stores with impaired iron delivery. 2 Initiate oral iron supplementation immediately and investigate source of iron loss. 2

Pattern 2: Normal/High Ferritin + Low TS + Elevated CRP/ESR

Anemia of chronic disease (inflammatory iron block). 2 Treat underlying inflammatory condition as primary intervention. 2

Pattern 3: Normal/High Ferritin + Low TS + Normal CRP/ESR

Functional iron deficiency—adequate storage iron but insufficient release to meet erythropoietic demands. 2 Consider soluble transferrin receptor (sTfR) testing to confirm real iron deficiency. 2

Pattern 4: High Ferritin + High TS

Iron overload—proceed with HFE genotyping for hemochromatosis. 1

Critical Pitfalls to Avoid

Never assume normal ferritin excludes iron deficiency in inflammatory states. 2, 3 Iron deficiency can coexist with ferritin levels up to 50-100 μg/L when inflammation is present. 2 In extreme cases, iron deficiency has been documented with ferritin >26,000 μg/L in adult-onset Still's disease. 3

Never interpret ferritin without TS. 1, 2 Ferritin reflects storage iron; TS reflects iron availability for erythropoiesis—both are required for complete assessment. 2

Recognize that ferritin >150 μg/L rarely occurs with absolute iron deficiency, even with inflammation. 2 If ferritin is this elevated with suspected iron deficiency, strongly consider alternative diagnoses including anemia of chronic disease, liver disease, or malignancy. 1, 2

Special Population Considerations

**For premenopausal women with iron deficiency anemia (Hb <12 g/dL, ferritin <45 ng/mL):** GI evaluation is conditional rather than mandatory. 1 Perform non-invasive testing for H. pylori and celiac disease first. 1 Reserve bidirectional endoscopy for those with GI symptoms, positive testing, age >50 years, or failure to respond to adequate oral iron after 8-10 weeks. 1, 2

For men and postmenopausal women with iron deficiency anemia: Bidirectional endoscopy is strongly recommended (moderate quality evidence) to evaluate for GI malignancy. 1

For chronic kidney disease patients on erythropoiesis-stimulating agents: Target ferritin >200 ng/mL and TS >20% to optimize hemoglobin response and reduce ESA requirements. 2 Functional iron deficiency may exist with ferritin 100-700 ng/mL if TS remains <20%. 2