What does transferrin indicate?

Transferrin as an Iron Status Indicator

Transferrin is a primary iron transport protein in the blood that indicates iron availability for erythropoiesis, with low transferrin saturation (<16%) suggesting iron deficiency and high saturation (>50%) suggesting iron overload. 1

Function and Significance of Transferrin

Transferrin serves as the main iron transport protein in blood plasma, with several key functions:

• Acts as a gatekeeper for regulating iron uptake by most cells 2
• Transports iron in a soluble, non-toxic form to tissues throughout the body 3
• Functions as an upstream regulator of hepcidin, the hormone that controls systemic iron traffic 3
• Maintains approximately 30% of its iron-binding capacity under normal conditions 4

Transferrin Measurements and Interpretation

Transferrin Saturation (TSAT)

• Calculated as: (Serum Iron ÷ TIBC) × 100% 1
• Normal reference range: 20-50% 1
• TSAT <16% suggests iron deficiency (specificity 93% for iron deficiency in non-pregnant women) 5, 1
• TSAT >50% suggests iron overload 1

Total Iron-Binding Capacity (TIBC)

• Measures the iron-binding capacity within serum and reflects available iron-binding sites on transferrin 5
• Increases when serum iron and stored iron are low 5
• Decreases when serum iron and stored iron are high 5
• Normal reference range: 100-300 μg/dL 1

Clinical Considerations

Factors Affecting Transferrin Measurements

• Diurnal variation: Transferrin saturation has greater day-to-day variation than hemoglobin or hematocrit 5, 1
• Inflammatory states: Infections and inflammation can decrease serum iron concentration 5, 1
• Medical conditions: Chronic infection, malignancies, liver disease, nephrotic syndrome, and malnutrition can lower TIBC readings 5
• Medications and hormones: Oral contraceptive use and pregnancy can raise TIBC readings 5
• Meal timing: Serum iron concentration increases after meals 5

Important Caveats

• Transferrin saturation is an indicator of iron-deficient erythropoiesis rather than iron depletion, making it less sensitive to changes in iron stores than serum ferritin 5
• For accurate assessment of iron status, transferrin saturation should be interpreted alongside other markers including serum ferritin, hemoglobin levels, and clinical context 1
• The sensitivity of low transferrin saturation (<16%) for iron deficiency is only 20%, despite its high specificity of 93% 5

Beyond Iron Transport

Transferrin has additional biological roles:

• Can potentially bind and transport other metal ions including Ti⁴⁺, V⁴⁺, Cr³⁺, Ru³⁺, Bi³⁺, and Mn³⁺ 4
• May transport potentially toxic metals such as Al³⁺ and actinide ions 4
• Acts as a growth factor through both iron-dependent and iron-independent mechanisms 6
• Plays an essential role in regulating hepcidin expression, which controls systemic iron homeostasis 7

Monitoring Recommendations

For patients at risk of iron overload, such as those with myelodysplastic syndromes receiving regular transfusions:

• Monitor serum ferritin and transferrin saturation regularly 5
• Consider tracking transfusion burden to help determine when to initiate chelation therapy 5
• Additional assessment methods like MRI or SQUID can be useful but are not essential 5