Transferrin is a glycoprotein comprising a polypeptide chain with two iron binding-sites; each site binds one ferric iron atom.1 Produced in hepatocytes, transferrin holds a key role in transporting iron to cells, in particular the bone marrow.1
Transferrin therefore another reservoir that holds iron when it is not otherwise held in storage by ferritin or in the heme form. The proportion of transferrin capacity (or total iron binding capacity, TIBC) that is utilized is termed the transferrin saturation. This is typically of the order of <50% in adults, meaning that only 50% of the total iron capacity within the transferrin reservoir is being utilized.
In laboratories the transferrin saturation is calculated using the serum iron and TIBC. TIBC is determined by assay of how much iron a quantum of blood can carry; it is therefore an indirect measure of transferrin. Mathematically, the transferrin saturation percentage is the ratio of the serum iron to the TIBC multiplied by 100.
Implications of transferrin and body iron
Transferrin when reported alongside serum ferritin may be useful in making the diagnosis of iron overload.2 Alone, it is not as useful as serum ferritin in monitoring long-term iron status,2 although it may be suggestive of an iron overload state if the transferrin saturation >50%.
Yet transferrin’s importance is in understanding the pathophysiology of iron overload. When the transferrin is fully saturated, iron in the plasma remains unbound in the circulation. Is this non-transferrin bound iron (NTBI) that gives rise to labile plasma iron (LPI)., which is associated with iron toxicity. A transferrin saturation level >80% can lead to the formation of LPI.2,3
- Brissot P, Ropert M, Le Lan C, et al. Non-transferrin bound iron: a key role in iron overload and iron toxicity. Biochim Biophys Acta. 2012;1820(3):403-410.
- Cabantchik ZI, Breuer W, Zanninelli G, et al. LPI-labile plasma iron in iron overload. Best Pract Res Clin Haematol. 2005;18(2):277-287.
- Loreal O, Gosriwatana I, Guyader D, et al. Determination of non-transferrin-bound iron in genetic hemochromatosis using a new HPLC-based method. J Hepatol. 2000;32(5):727-733.