The laboratory tests used to assess iron status are shown in Table 3.1. The next sections examine these various tests in more detail.
Transferrin (Total Iron-Binding Capacity or TIBC)
Transferrin is the major iron transport protein in the body. Its role is to shuttle iron from storage sites and the gut to the erythroid marrow where the iron that's carried can be used for hemoglobin synthesis. Transferrin is the only major iron transporter to parenchymal cells. The amount of iron transported to non-erythroid tissues is proportional to the serum iron and, thus,
Table 3.1. Tests used to assess iron status
1. Serum iron and total iron binding capacity (TIBC; transferrin) from which the percent transferrin saturation is calculated
3. Soluble transferrin receptor (sTfR) protein the percent transferrin saturation. A common misconception is that trans-ferrin is an acute phase protein. It is a better reflection of nutritional status. However, over time, transferrin levels are related inversely to total body iron stores (4). The measurement of transferrin is a direct measurement of the protein. But from a practical point of view, the physician typically orders a TIBC, which is a functional measurement of the amount of iron that the plasma is capable of binding. The TIBC is a derived value, combining the total serum iron and the unsaturated IBC. From this, one calculates the percent transferrin saturation.
Ferritin is produced widely throughout the body but mostly in liver cells. Ferritin is also made by erythroid and reticuloendothelial cells and functions as an iron binding protein for storage; it is not a transport protein as is transferrin. In fact, it would perhaps be more accurate to refer to serum ferritin as serum a^o-ferritin, since very little iron is actually bound by circulating ferritin under normal conditions.
The serum ferritin level is much maligned because ferritin is an acute phase reactant and becomes elevated with inflammation. Nevertheless, the serum ferritin is the best laboratory test available to estimate total body iron stores. The validity of this concept was established years ago when normal individuals were subjected to serial phlebotomies to create a state of iron deficiency (5). The amount of iron removed (each unit of whole blood contains approximately 220 mg of elemental iron) was then correlated with the initial plasma ferritin level. As shown in Fig. 3.1, there was a very good correlation between the amount of iron removed and the initial ferritin value.
Soluble Transferrin Receptor Protein (sTfRP)
Transferrin receptors (TfR) are found primarily on erythroid tissues and this tissue normally accounts for about 80% of the number of TfR in the body. TfR are also found on liver cells and expressed on any cell during
development at a time when iron is required for growth. The TfR is recycled within developing erythroid cells, and a certain proportion is shed into the circulation as soluble TfR protein (Fig. 3.2; 2) . Thus, the amount of sTfR protein is proportional to the size of the erythroid marrow (6). However, in states of iron deficiency, the TfR gene is upregulated, and increased numbers of TfR are expressed on the surface of developing erythroid cells.
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