What is iron saturation?

Understanding Iron Saturation

Transferrin saturation (TSAT) is a measure that indicates the extent to which transferrin has vacant iron-binding sites, calculated by dividing serum iron concentration by total iron-binding capacity (TIBC) and multiplying by 100 to express the result as a percentage. 1

Calculation and Formula

• TSAT is calculated using the formula: TSAT (%) = (serum iron / TIBC) × 100 1
• TIBC is a measure of the iron-binding capacity within the serum and reflects the availability of iron-binding sites on transferrin 2
• Transferrin can be converted to TIBC using the formula: TIBC (μmol/L) = Transferrin (g/L) × 25.1 1

Clinical Interpretation

• Normal TSAT range in adults is typically 20-50% 1
• Low TSAT (<20%) indicates a high proportion of vacant iron-binding sites and is often used to confirm iron deficiency 2, 3
• High TSAT (>50%) may indicate iron overload conditions 1
• TSAT is an indicator of iron-deficient erythropoiesis rather than iron depletion 2
• TSAT is less sensitive to changes in iron stores than serum ferritin concentration 2

Diagnostic Significance

• Among adults, a TSAT of less than 16% is commonly used to confirm iron deficiency 2, 3
• In chronic kidney disease patients, even those with normal TSAT but low serum iron are at risk for anemia 4
• In heart failure patients, low TSAT is significantly associated with adverse outcomes, more strongly than ferritin concentrations 5

Factors Affecting TSAT Measurement

• Diurnal variation: TSAT levels rise in the morning and fall at night 2
• Recent meals: Serum iron concentration increases after each meal, affecting TSAT 2
• Inflammation and infection: Can decrease serum iron concentration and affect TSAT 2, 1
• Day-to-day variation: TSAT has greater variation within individuals than hemoglobin concentration 2, 1
• Other conditions affecting TIBC and thus TSAT include: 2
  • Chronic infection
  • Malignancies
  • Liver disease
  • Nephrotic syndrome
  • Malnutrition
  • Oral contraceptive use
  • Pregnancy

Limitations and Considerations

• The cost of assessing transferrin saturation and unavailability of simple, clinic-based methods can hinder its use in screening for iron deficiency 2
• In inflammatory states, TSAT may be more reliable than ferritin, as ferritin is an acute-phase reactant that can be elevated independent of iron status 6
• In patients with multiple comorbidities, interpreting TSAT and ferritin can be challenging, particularly when ferritin is high (suggesting iron overload) but TSAT is low (suggesting iron deficiency) 6
• Some studies suggest that TSAT may be more informative than arbitrary definitions of iron deficiency based on combined ferritin and TSAT cutoffs 5
• Alternative markers for iron status that may be useful when TSAT and ferritin are insufficient include reticulocyte hemoglobin content, percentage of hypochromic red cells, and soluble transferrin receptor 6

Clinical Application

• Laboratory evaluation following IV iron should include a CBC and iron parameters (ferritin, TSAT) 4 to 8 weeks after the last infusion 2
• Iron parameters should not be evaluated within 4 weeks of a total dose iron infusion, as circulating iron interferes with the assay 2
• A goal TSAT of ≥20% is generally desired to ensure adequate iron for erythropoiesis 2, 3