Clinical and Interpretive

Screening for chronic iron overload diseases, particularly hereditary hemochromatosis

Ingested iron is absorbed primarily from the intestinal tract and is temporarily stored in the mucosal cells as ferritin (Fe[III]). Ferritin provides a soluble protein shell to encapsulate a complex of insoluble ferric hydroxide-ferric phosphate. On demand, iron is released into the blood by mechanisms that are not clearly understood, to be transported as Fe(III)-transferrin.

Transferrin is the primary plasma iron transport protein, which binds iron strongly at physiological pH. Transferrin is generally only 25% to 30% saturated with iron. The additional amount of iron that can be bound is the unsaturated iron-binding capacity (UIBC). The total iron-binding capacity (TIBC) can be indirectly determined using the sum of the serum iron and UIBC. Knowing the molecular weight of the transferrin and that each molecule of transferrin can bind 2 atoms of iron, TIBC and transferrin concentration is interconvertible.

Percent saturation (100 x serum iron/TIBC) is usually normal or decreased in persons who are iron deficient, pregnant, or are taking oral contraceptive medications. Persons with chronic inflammatory processes, hemochromatosis, or malignancies generally display low transferrin.

Serum iron, total iron-binding capacity, and percent saturation are widely used for the diagnosis of iron deficiency. However, serum ferritin is a much more sensitive and reliable test for the demonstration of iron deficiency.

CAUTIONS 

Measurement of serum iron, iron-binding capacity, and percent saturation should not be used as a test for iron deficiency. It is often unreliable for this purpose.