Transferrin

Transferrin is a serum protein whose function is to transport iron in the blood; more specifically, each molecule of transferrin binds two Fe³⁺ ions with high affinity. Transferrin binds to transferrin receptors on cells which require iron, after which the transferrin-transferrin receptor complex is endocytosed. The pure protein, non-iron-bound form of transferrin is called apoferritin. Transferrin is a negative acute phase protein.

The liver up-regulates the synthesis of transferrin in case of long-term iron deficiency.

Transferrin in laboratory medicine

Transferrin is measured clinically as a surrogate for the body's iron stores. It's not necessary to measure routinely in the evaluation of iron status, as a decreased ferritin level is sufficient for the diagnosis. There is some diurnal variation, so it should be measured in the morning.

As a negative acute phase protein, it'll be falsely low in case of infection or inflammation. Elevated levels of transferrin indicates long-term iron deficiency.

Soluble transferrin receptor

While transferrin receptor is mainly found on cell surfaces, a number of free (soluble) transferrin receptors (s-TfR) can be found in the serum as well. This is mostly from the extracellular part of the receptor of immature erythrocytes being proteolytically cleaved when the erythrocytes mature. The level of soluble transferrin receptor in the serum is proportional to the total number of transferrin receptor in tissues.

Because the soluble transferrin receptor is not an acute phase protein, its level is unaffected by the acute phase and therefore by inflammation and infection. This makes s-TfR good to evaluate iron status in patients who currently have inflammation or infection.

Elevated s-TfR levels (> 4.3 mg/L) indicate iron deficiency.

Transferrin saturation and TIBC

Transferrin can also be used to calculate transferrin saturation and total iron binding capacity (TIBC). Transferrin saturation measures how much of the serum transferrin is saturated with iron. TIBC measures how much iron the transferrin in the serum could bind at max. However, normally, practically 100% of serum transferrin is saturated with iron. Because each molecule of transferrin can bind two Fe³⁺ molecules, TIBC is calculated as 2 x serum transferrin level. Then, the transferrin saturation can be calculated as serum iron divided by TIBC.

Transferrin saturation and TIBC is not necessary to diagnose iron deficiency; ferritin alone is sufficient for that. A decreased transferrin saturation indicates iron deficiency and is less affected by acute phase than ferritin.

Both transferrin saturation and TIBC can be used in the evaluation and follow-up of haemochromatosis.