Iron overload and associated abnormalities can be detected by diverse biochemical and physicochemical tests. It is also possible to predict susceptibility to develop iron overload in some persons by the appropriate selection and interpretation of molecular genetic analyses. In this chapter, the clinical and laboratory assessment of iron overload is reviewed.

Transferrin and transferrin saturation

Transferrin is a ~80 kDa metal-binding glycoprotein synthesized by hepatocytes. It is the predominant iron transporter in plasma, and is responsible for the capture, transport, and distribution of free iron. Each molecule of transferrin has two high-affinity iron-binding sites, each of which can bind one ferric ion. Iron binding to transferrin is maximal at alkaline values of pH, and in the presence of bicarbonate. Transferrin binds iron absorbed via enterocytes and iron that is released by macrophages and hepatocytes. In healthy subjects, much transferrin-bound iron is delivered to erythroblasts in the bone marrow for hemoglobin synthesis via specific transferrin receptors (Chapter 2). Transferrin also transports iron to other tissues that accept iron via similar receptors. In normal subjects, approximately eight times the amount of plasma iron quantified in static measurements is delivered by transferrin to target cells each day. Transferrin also binds and transports certain non-ferrous metals (Chapter 8).

Normal subjects

The capacity of serum transferrin to bind iron is measured by automated clinical laboratory methods as the serum total iron-binding capacity (TIBC). Typically, this is calculated as the sum of the serum iron concentration and the serum unbound iron-binding capacity (UIBC).