What is the difference between ferritin and transferrin lab testing in assessing iron stores and iron deficiency anemia?

Ferritin vs Transferrin Testing in Assessing Iron Stores and Iron Deficiency Anemia

Serum ferritin is the most specific test for iron deficiency in the absence of inflammation, while transferrin and transferrin saturation provide complementary information particularly valuable when inflammation is present. 1

Key Differences Between Ferritin and Transferrin Testing

Ferritin

• Reflects iron stores in the liver, spleen, and bone marrow reticuloendothelial cells 2
• Each 1 μg/L (ng/mL) of serum ferritin corresponds to approximately 10 mg of stored iron 2
• Most specific marker for iron deficiency when inflammation is absent 1
• Interpretation thresholds:
  • <15 μg/L: Highly specific for iron deficiency (specificity 0.99) 1
  • <30 μg/L: Generally indicative of low body iron stores 1
  • <45 μg/L: Provides optimal trade-off between sensitivity (85%) and specificity (92%) for iron deficiency 1

  • 150 μg/L: Iron deficiency unlikely even with inflammation 1

• Major limitation: Acts as an acute phase reactant, leading to falsely elevated levels during inflammation 1, 2

Transferrin and Related Parameters

• Transferrin: Iron transport protein that increases in iron deficiency 1
• Transferrin saturation: Percentage of transferrin binding sites occupied by iron 1
• Low transferrin saturation (<20%) indicates inadequate iron availability for erythropoiesis 1
• Serum transferrin receptor (sTfR): Increases with tissue iron deficiency and is not affected by inflammation 3, 4
• Advantages of transferrin-related parameters:
  • Not significantly affected by inflammation 3
  • Better reflects functional iron availability 4
  • Helps distinguish between iron deficiency anemia and anemia of chronic disease 5, 3

Combined Approaches for Enhanced Diagnostic Accuracy

sTfR/log(ferritin) Ratio

• Superior to either parameter alone for diagnosing iron deficiency, particularly in inflammatory states 1, 5
• Provides complete separation between IDA and non-IDA populations at a cut-off of 1.70 6
• Especially valuable when ferritin levels are in the inconclusive range (20-100 μg/L) 6, 5

Transferrin/log(ferritin) Ratio

• Practical tool that improves diagnosis when ferritin levels are inconclusive 6
• At a cut-off value of 1.70, can identify IDA in 29% of patients with inconclusive ferritin levels 6

Clinical Application Algorithm

1. Initial Assessment:

   • Check serum ferritin as first-line test 1, 4
   • If ferritin <15 μg/L: Definite iron deficiency (specificity 99%) 1
   • If ferritin >150 μg/L: Iron deficiency unlikely 1

2. For inconclusive ferritin (15-150 μg/L):

   • Check for inflammation (C-reactive protein) 1
   • Measure transferrin saturation (TSAT) 1
   • Consider sTfR or sTfR/log(ferritin) ratio 1, 5

3. Interpretation with inflammation present:

   • Ferritin <100 μg/L may still indicate iron deficiency 1
   • TSAT <20% with ferritin 30-100 μg/L suggests combined iron deficiency and anemia of chronic disease 1
   • sTfR or sTfR/log(ferritin) ratio provides better discrimination than ferritin alone 5, 3

Common Pitfalls to Avoid

• Relying solely on ferritin in patients with inflammation or chronic disease 1, 2
• Using only MCV or MCH for diagnosis, as they lose sensitivity in chronic disease, thalassemia, or vitamin B12/folate deficiency 1
• Failing to consider combined iron deficiency and anemia of chronic disease when ferritin is 30-100 μg/L 1
• Not investigating non-anemic iron deficiency (NAID) in high-risk populations (men, postmenopausal women, GI symptoms) 1

Special Considerations

• In chronic kidney disease: Maintain ferritin >100 μg/L 2
• In inflammatory bowel disease: Consider IV iron when ferritin <100 μg/L or hemoglobin <120-130 g/L 1
• In premenopausal women with NAID: GI investigation generally not warranted unless other concerning features present 1
• In men and postmenopausal women with IDA: GI investigation (gastroscopy and colonoscopy) recommended 1