Understanding Iron Saturation Index
Iron saturation index, more commonly known as transferrin saturation, is a percentage calculated by dividing serum iron concentration by total iron-binding capacity (TIBC) and multiplying by 100, which indicates the proportion of transferrin binding sites occupied by iron. 1
Definition and Calculation
Transferrin saturation is calculated using the following formula:
Transferrin saturation (%) = [serum iron concentration (μg/dL) / TIBC (μg/dL)] × 100 1
This measurement represents:
- The extent to which transferrin has vacant iron-binding sites
- A low transferrin saturation indicates a high proportion of vacant iron-binding sites
- A high transferrin saturation indicates more binding sites are occupied by iron
Clinical Significance
Transferrin saturation is an important marker in assessing iron status:
Iron deficiency: A transferrin saturation of less than 16% among adults is often used to confirm iron deficiency 1
- In nonpregnant women of childbearing age, this cutoff has a sensitivity of 20% and specificity of 93% for iron deficiency 1
Iron overload: Elevated transferrin saturation may indicate iron overload conditions 2
Heart failure: Low transferrin saturation is significantly associated with adverse outcomes in heart failure patients, more strongly than ferritin levels 3
Factors Affecting Measurement
Several factors can affect transferrin saturation results:
- Diurnal variation: Iron levels typically rise in the morning and fall at night 1
- Meal timing: Serum iron concentration increases after meals 1
- Inflammatory states: Infections and inflammation can decrease serum iron concentration 1
- Medical conditions: Chronic infection, malignancies, liver disease, nephrotic syndrome, and malnutrition can lower TIBC readings 1
- Medications/hormones: Oral contraceptive use and pregnancy can raise TIBC readings 1
Limitations
Transferrin saturation has several limitations as a diagnostic test:
- It has greater day-to-day variation than hemoglobin concentration or hematocrit 1
- It is an indicator of iron-deficient erythropoiesis rather than iron depletion 1
- It is less sensitive to changes in iron stores than serum ferritin concentration 1
- The cost and unavailability of simple, clinic-based methods limit its use in screening 1
Clinical Application
When evaluating iron status, transferrin saturation should be interpreted alongside other markers:
- Serum ferritin (storage form of iron)
- Hemoglobin levels
- Total iron-binding capacity (TIBC)
- Clinical context (inflammation, pregnancy, etc.)
For optimal diagnostic accuracy:
- A transferrin saturation of <7% has been shown to have a positive likelihood ratio of 21.62, with a specificity of 98.0% and positive predictive value of 93.8% for iron deficiency in acute care hospital settings 4
- Some researchers have proposed using a transferrin index (Fe/transferrin) as an alternative to transferrin saturation, which may provide better precision in screening for iron overload 5
Common Pitfalls
- Relying solely on transferrin saturation: No single iron parameter has both high sensitivity and specificity (>80%) 6
- Ignoring inflammatory status: Inflammation affects most iron parameters including transferrin saturation 1
- Disregarding timing: Due to diurnal variation, consistent timing of blood draws is important 1
- Inconsistent laboratory methods: Different methods for measuring iron parameters can affect reference ranges and comparability 2