Iron Transferrin and Percent Saturation

Iron is necessary for the production and function of hemoglobin and myoglobin. It also plays critical roles in mitochondrial energy production and neurotransmitter synthesis. The recommended daily intake of iron is 18 mg per day for women, but the average intake in the United States is approximately 13 mg/day. Iron deficiency affects approximately 2 billion people worldwide and 14% of adults in the United States. 

Iron is absorbed from the diet. The most efficiently absorbed form is heme iron, derived from red meat, poultry, and seafood. Nonheme iron is available from legumes and vegetables (dried beans, dark leafy greens) and supplemented cereals. Both forms of iron are absorbed by intestinal enterocytes and transported via the iron exporter protein, ferroportin, to transferrin in the blood. Transferrin transports iron to the liver and spleen for storage as ferritin. Transferrin also transports iron to the bone marrow where it is stored as  hemosiderin. Iron is also salvaged from senescent red blood cells by macrophages and stored in the reticuloendothelial system. Approximately 1 to 2 mg of iron is lost each day in sweat and feces.

Iron needs of the body are met by dietary intake averaging 1520 mg/day. Only ferrous iron can be absorbed. Transferrin is the plasma iron transport protein. Normally, it is only 25-30% saturated with iron. Transferrin bound iron is largely derived from hemoglobin breakdown. 

The most common causes of iron deficiency are bleeding (menstrual and gastrointestinal), impaired iron absorption (atrophic gastritis, celiac disese, bariatric surgery), inadequate dietary intake, and pregnancy. During the third trimester of pregnancy, up to 84% of women develop iron deficiency. Additional risk factors include use of nonsteroidal anti-inflammatory drugs, inflammatory bowel disease, chronic kidney disease, and cancer. 

Iron deficiency progresses from low iron stores to iron deficiency anemia. Absolute iron deficiency is defined as serum ferritin less than 30 ng/dL or transferrin saturation (TSAT) less than 16%-20%. TSAT is calculated as iron/transferrin x 1.2. Iron deficiency anemia is defined as ferritin less than 30 ng/mL, or TSAT less than 20%, and a hemoglobin level less than 12 g/dL in women and less than 13 g/dL in men. 

Serum iron and transferrin saturation are commonly used to screen for iron deficiency and iron overload disorders. The degree of transferrin saturation is a very sensitive indicator of functional iron depletion. Iron concentration and percent saturation decrease with iron deficiency. Transferrin saturation is usually less than 16% in iron deficiency. A threshold of 20% is often used for patients with inflammation. When screening for iron deficiency, serum ferritin should also be ordered because it is a more sensitive and reliable test for iron deficiency. 

Transferrin saturation is a better screening test for hereditary hemochromatosis than ferritin. In hereditary hemochromatosis, serum iron is usually above 150 ug/dL and transferrin saturation exceeds 60%.

• Increased serum iron may be associated with hemolysis, transfusion, hemochromatosis, hemosiderosis, and hepatitis.  
• Decreased serum iron may be associated with chronic hemorrhage, dietary deficiency, anemia of chronic disease ,and uremia. 
• Increased total iron binding capacity (or transferrin) may be associated with iron deficiency, hepatitis, pregnancy and the administration of estrogen.
• Decreased total iron binding capacity may be associated with pernicious anemia, hemochromatosis, uremia, acute and chronic inflammation and protein malnutrition.

Causes of an elevated transferrin saturation and a normal ferritin level include:

• Iron supplements or iron-rich meal prior to blood draw
• Hereditary hemochromatosis being treated with phlebotomy
• Hereditary hemochromatosis and menstruation
• Very low TIBC due to severe liver disease (ferritin may be increased)
• Acute hemolysis

Serum iron, and therefore iron saturation exhibit biological variation due to diurnal variation and post-prandial effects. Levels can vary by 25-30% from day to day.  

Reference range for serum iron is 50-150 mg/dL in males and 25-145 ug/dL in females. Reference range for transferrin is 200-360 mg/dL. 

Percent saturation is calculated with the following formula: Iron/transferrin x 1.2.  The reference range for percent saturation is 15-50%.  

Specimen requirement is one SST tube of blood

Please read the article on "Iron Deficiency" for more information on iron, transferrin, and transferrin saturation.

References

Markowitz H, Fairbanks VF: Transferrin assay and total iron binding capacity. Mayo Clin Proc 1983;58:827-828

Szoke D, Panteghini M: Diagnostic value of transferrin. Clin Chim Acta 2012 Aug 16;413(15-16):1184-1189