How do I interpret serum iron, ferritin, and total iron‑binding capacity (TIBC) results in an adult patient?

Interpretation of Serum Iron, Ferritin, and TIBC

Interpret these three tests together as a panel, never in isolation, because each marker has significant limitations when used alone—ferritin is the most reliable single test for iron deficiency in the absence of inflammation, while transferrin saturation (calculated from serum iron and TIBC) provides the best functional assessment of iron availability. 1

Core Components and What They Measure

Serum Iron

• Measures the amount of circulating iron bound to transferrin at a single point in time 1
• Normal range: 50–175 μg/dL 1
• Critical limitation: Exhibits marked day-to-day variability, diurnal fluctuation (highest in morning), and is affected by recent meals, inflammation, and infection 2, 3
• Low serum iron alone is unreliable for diagnosing iron deficiency due to poor diagnostic accuracy 2

Total Iron-Binding Capacity (TIBC)

• Measures the maximum amount of iron that transferrin can bind 1
• Normal range: 250–370 μg/dL (45–66 mmol/L) 1
• Increases when iron stores are depleted as the body produces more transferrin to capture any available iron 1, 2
• Decreases in chronic inflammation, malnutrition, and iron overload 3

Serum Ferritin

• Reflects total body iron stores 1
• Normal range: 20–250 μg/L (men), 20–200 μg/L (women) 1
• Most specific single test for iron deficiency in the absence of inflammation 1
• Critical caveat: Ferritin is an acute-phase reactant that rises with inflammation, infection, liver disease, and malignancy, potentially masking iron deficiency 1, 3

Transferrin Saturation (TSAT)

• Calculated as: (Serum Iron ÷ TIBC) × 100 1
• Normal range: 20–50% 1
• Provides the best functional assessment of iron availability for erythropoiesis 2

Diagnostic Algorithm for Iron Deficiency

Step 1: Calculate Transferrin Saturation and Apply Initial Criteria

Iron deficiency is highly likely when:

• TSAT <16% **AND** TIBC >70 μmol/L (>390 μg/dL) → 93% predictive value for iron deficiency 2, 4
• Proceed directly to treatment if ferritin <30 μg/L and no inflammation present 1, 2

Iron deficiency is highly unlikely when:

• TSAT ≥22% AND TIBC ≤70 μmol/L (≤390 μg/dL) → 99% predictive value for normal iron status 2, 4
• No further iron studies needed in this scenario 4

Step 2: Interpret Ferritin in Clinical Context

Without inflammation (normal CRP):

• Ferritin <15 μg/L → 99% specificity for absent iron stores 1
• Ferritin <30 μg/L → Confirms iron deficiency 1, 2
• Ferritin 30–45 μg/L → Consider iron deficiency, especially with TSAT <20% 1

With inflammation present:

• Ferritin <45 μg/L → Iron deficiency likely (specificity 92%) 1
• Ferritin <100 μg/L → May still indicate iron deficiency despite "normal" appearance 2, 3
• Ferritin >150 μg/L → Iron deficiency unlikely even with inflammation 1

Step 3: Recognize Common Patterns

Pattern	Serum Iron	TIBC	TSAT	Ferritin	Interpretation
Iron Deficiency	↓	↑	<16–20%	<30 μg/L	Depleted iron stores [1]
Anemia of Chronic Disease	↓	↓ or normal	Variable	Normal or ↑	Inflammation blocks iron utilization [1]
Iron Overload/Hemochromatosis	↑	↓	>45–50%	>200 (F) or >300 (M) μg/L	Excess iron stores [1,3]
Thalassemia	Normal or ↑	Normal or ↓	Normal or ↑	Normal or ↑	Microcytosis without iron deficiency [1]

Critical Pitfalls to Avoid

Do Not Rely on Serum Iron or TIBC Alone

• Serum iron and TIBC provide no additional diagnostic information beyond TSAT and ferritin when all tests are available 5
• These tests are redundant if ferritin can be measured 5

Do Not Dismiss Iron Deficiency Based on "Normal" Ferritin

• In inflammatory states, ferritin up to 100 μg/L may still represent true iron deficiency 2, 3
• Always correlate ferritin with TSAT and clinical context 1

Do Not Order Tests at Suboptimal Times

• Obtain fasting morning samples when possible to minimize diurnal variation 3
• Avoid testing immediately after meals, which can falsely elevate serum iron 2, 3

Do Not Ignore the Need to Find the Underlying Cause

• Iron deficiency mandates investigation for blood loss (GI bleeding, menorrhagia), malabsorption (celiac disease), or inadequate intake 2
• In men and postmenopausal women, always investigate for GI malignancy with endoscopy if ferritin ≤44 ng/mL or TSAT ≤9% 6
• Screen for celiac disease in all cases (found in 3–5% of iron deficiency) 1

When Results Are Equivocal

If iron studies remain unclear despite complete panel:

• Measure soluble transferrin receptor (sTfR) or reticulocyte hemoglobin content if available 1
• Consider hepcidin measurement in specialized centers, particularly when inflammation complicates interpretation 1
• Bone marrow biopsy with iron staining remains the gold standard when definitive diagnosis is essential 1, 3

Special Considerations

In Chronic Kidney Disease

• Different thresholds apply: absolute iron deficiency defined as TSAT ≤20% with ferritin ≤100 μg/L 2
• Functional iron deficiency can occur with adequate stores but impaired mobilization 2

After IV Iron Therapy

• Wait 4–8 weeks after last infusion before rechecking iron parameters to avoid assay interference 3

In Suspected Hemochromatosis

• TSAT >45% with ferritin >200 μg/L (women) or >300 μg/L (men) warrants genetic testing for HFE mutations 1
• Evaluate for cardiac and hepatic complications if ferritin >1,000 μg/L 1, 3