What is the difference between transferrin and ferritin in assessing iron status?

Transferrin vs Ferritin in Assessing Iron Status

Transferrin saturation (TSAT) reflects iron readily available for erythropoiesis, while ferritin reflects iron storage levels, making both measurements essential for comprehensive iron status assessment. 1

Key Differences Between Transferrin and Ferritin

• Transferrin measures circulating iron available for immediate use:

  • Calculated as (serum iron × 100) ÷ total iron binding capacity (TIBC) 1
  • Reflects iron that is readily available for erythropoiesis 1
  • Low TSAT (<20%) indicates limited iron availability for red blood cell production 1
  • More strongly associated with clinical outcomes in conditions like heart failure than ferritin 2

• Ferritin measures iron storage:

  • Reflects iron stored in liver, spleen, and bone marrow reticuloendothelial cells 1
  • Direct relationship with body iron stores (1 μg/L ≈ 10 mg stored iron) 1
  • Highly specific for iron deficiency when very low 1
  • Acts as an acute phase reactant, increasing during inflammation regardless of iron status 1, 3

Clinical Interpretation

Diagnosing Iron Deficiency

• Absolute Iron Deficiency:

  • Traditionally defined as ferritin <12 ng/mL with TSAT <16% in healthy subjects 1
  • In chronic kidney disease (CKD): ferritin <100 ng/mL and TSAT <20% 1
  • Serum ferritin <15 μg/L has 75% sensitivity and 98% specificity for iron deficiency 1

• Functional Iron Deficiency:

  • Occurs when iron demand exceeds release from stores 1
  • TSAT <20% with normal or elevated ferritin (100-700 ng/mL) 1
  • Common during erythropoietin therapy 1

Confounding Factors

• Inflammation affects both markers differently:

  • Ferritin increases as an acute phase reactant, potentially masking iron deficiency 1, 3
  • TSAT typically decreases during inflammation 1
  • In obesity, ferritin correlates more strongly with inflammation markers than with iron status 3

• Diurnal variation:

  • Serum iron (and thus TSAT) shows diurnal variation, rising in morning and falling at night 1
  • Ferritin is more stable throughout the day 1

Clinical Applications

Chronic Kidney Disease

• Recommended targets:
  • Serum ferritin >100 ng/mL (no upper limit specified) 1
  • TSAT >20% 1
  • Higher ferritin targets (>200 ng/mL) associated with lower erythropoietin requirements 1

Heart Failure

• Iron deficiency defined as:
  • Ferritin <100 ng/mL or 100-300 ng/mL with TSAT <20% 1
  • Low TSAT more strongly associated with mortality than ferritin levels 2
  • TSAT shows stronger association with outcomes in heart failure with preserved ejection fraction 2

Inflammatory Conditions

• Diagnostic challenges:
  • When ferritin is 100-700 ng/mL with TSAT <20%, difficult to distinguish functional iron deficiency from inflammatory block 1
  • Consider additional markers like soluble transferrin receptor, which remains normal in functional iron deficiency but increases in true iron deficiency 1, 4

Advanced Iron Assessment Tools

• Reticulocyte hemoglobin content (CHr):

  • CHr <30 pg predictive of response to IV iron 1
  • Provides insight into adequacy of iron supply to developing red cells 1

• Percentage of hypochromic red cells:

  • Values >10% compatible with iron deficiency in erythropoietin-treated patients 1
  • Sensitive indicator for functional iron deficiency 1

• Transferrin/log(ferritin) ratio:

  • Improves diagnosis when ferritin levels are inconclusive (20-100 μg/L) 5
  • At cut-off value of 1.70, can help identify iron deficiency when other markers are unclear 5

Common Pitfalls to Avoid

• Relying solely on ferritin:

  • May miss iron deficiency in inflammatory states 1, 3
  • Consider ferritin an unreliable marker in obesity, infection, or inflammation 3

• Ignoring clinical context:

  • Interpretation should consider hemoglobin levels, erythropoietin dose, and patient status 1
  • Iron therapy may not be required if hemoglobin is above target despite slightly low iron indices 1

• Using outdated cutoffs:

  • Traditional ferritin cutoffs (<20 μg/L) may miss many cases of iron deficiency 5
  • Some evidence suggests optimal ferritin levels for cardiovascular outcomes may be 20-100 ng/mL 6