Clinical Information

Transferrin is the plasma iron transport protein that binds iron strongly to keep iron nonreactive in circulation and deliver it to cells with transferrin receptors. The rate of transferrin synthesis in the liver can be altered according to the body’s iron requirements and iron reserves. The circulating concentration increases in response to iron deficiency and decreases in response to iron overload. Transferrin is generally only 25% to 30% saturated with iron. Total iron-binding capacity (TIBC) is estimated from the transferrin concentration using the molecular weight of transferrin, accounting for each transferrin molecule that can bind 2 atoms of iron.

Iron deficiency, iron overload, and anemia of chronic disease are the most prevalent disorders of iron metabolism. Serum iron, TIBC, and percent saturation are widely used for the diagnosis of iron deficiency and iron overload disorders, such as hemochromatosis. Iron concentration and percent saturation decrease with iron deficiency and increase when iron is in excess. However, serum ferritin is a much more sensitive and reliable test for demonstration of iron deficiency.

Anemia of chronic disease is often observed in patients with autoimmune diseases, chronic kidney diseases, inflammatory bowel disease, and chronic heart failure. It is  diagnosed when serum iron concentrations are low despite normal serum ferritin concentrations  indicating adequate iron stores. However, in the presence of inflammation, ferritin can mask iron deficiency; therefore, measuring soluble transferrin receptors is suggested.

The biologic variation of iron and, therefore, iron saturation is notable in normal healthy persons and in various clinical disorders owing to both diurnal variation and post-prandial effects. The intraindividual day-to-day variation of iron and iron saturation is approximately 25% to 30%.(1) Recommendations for blood sampling for iron and iron saturation measurements are contradictory; however, minimizing influence of these effects can be accomplished by collecting during the morning after an overnight fast.