Is total iron the same as serum ferritin?

No, Total Iron and Serum Ferritin Are Not the Same

Serum iron measures the amount of iron currently circulating in the bloodstream bound to transferrin, while serum ferritin reflects iron stored in the liver, spleen, and bone marrow—they assess completely different aspects of iron metabolism. 1

Key Distinctions Between These Markers

What Each Test Measures

• Serum iron quantifies iron in transit through the bloodstream, representing iron immediately available for red blood cell production 1
• Serum ferritin indicates storage iron contained within reticuloendothelial cells, serving as the most reliable indicator of total body iron stores 1, 2
• The relationship is approximately 1 μg/L of serum ferritin equals 10 mg of stored iron 2

Clinical Stability and Reliability

• Serum ferritin shows significantly less day-to-day variation (average coefficient of variation 14.5%) compared to serum iron (28.5%), making a single ferritin measurement more reliable than isolated serum iron determination 3
• Serum iron exhibits marked diurnal variation throughout the day, which can affect interpretation if samples are not collected at consistent times 1
• Serial measurements of serum iron must account for timing relative to clinic or dialysis visits to ensure accuracy 1

How They Work Together in Diagnosis

Complementary Assessment

• Neither marker alone provides a complete picture of iron status—they must be interpreted together to distinguish between absolute iron deficiency, functional iron deficiency, and inflammatory iron block 1, 2
• Serum iron is used to calculate transferrin saturation (TSAT) using the formula: (serum iron × 100) ÷ total iron binding capacity (TIBC) 2
• TSAT reflects iron readily available for erythropoiesis, while ferritin reflects storage reserves 1

Diagnostic Patterns

• Absolute iron deficiency: Both depleted stores (ferritin <100 ng/mL in chronic kidney disease, <15 μg/L in general population) AND impaired delivery (TSAT <20%) 1, 2
• Functional iron deficiency: Normal or elevated ferritin but insufficient iron release to meet demands, resulting in low TSAT despite adequate stores 1
• Inflammatory iron block: Sudden ferritin increase with TSAT drop, distinguishable from functional deficiency by the abrupt pattern change 1

Critical Clinical Pitfalls

Ferritin as an Acute Phase Reactant

• Ferritin increases during inflammation, infection, or tissue damage independently of iron status, potentially masking depleted stores 1, 2
• In patients with inflammation, true iron deficiency may be present even with ferritin levels up to 50-100 μg/L 2
• Values >150 μg/L rarely occur with absolute iron deficiency, even in inflammatory conditions 2

Serum Iron Limitations

• Serum iron reflects only circulating iron, not total body stores, and can be normal even when storage iron is severely depleted 2
• The high day-to-day variability (28% coefficient of variation) makes single measurements less reliable for assessing iron status 3

When Results Are Discordant

• If ferritin and TSAT are contradictory or inflammation is present, soluble transferrin receptor (sTfR) should be used as the first-line alternative marker 4
• The percentage of hypochromic red blood cells (>10%) is particularly valuable in erythropoietin-treated patients when standard markers are unreliable 4
• Do not measure iron parameters within 4 weeks of total dose iron infusion, as circulating iron interferes with assays and produces spurious results 4

Diagnostic Algorithm for Iron Status

1. Measure both ferritin and serum iron/TSAT together at the same time point 1, 2
2. If ferritin <15 μg/L: Absolute iron deficiency confirmed regardless of serum iron 2
3. If ferritin 15-100 μg/L with TSAT <20%: Check inflammatory markers (CRP/ESR) to distinguish functional deficiency from inflammatory block 1, 2
4. If ferritin >100 ng/mL with TSAT <20%: Consider trial of IV iron (50-125 mg weekly for 8-10 doses) to distinguish functional deficiency from inflammatory block—response indicates functional deficiency, no response indicates inflammation 1
5. If results remain unclear: Add sTfR or hypochromic RBC percentage for definitive assessment 4