Transferrin Saturation

Transferrin saturations of less than 20% indicate iron deficiency, while transferrin saturations of more than 50% suggest iron overload.

The terms transferrin saturation and iron-binding capacity, saturation, are interchangeable; however, this value is now most commonly referred to simply as transferrin saturation. This minimizes confusion with another value, iron-binding capacity, which is used when determining a patient’s iron status.

The reference range for transferrin saturation is as follows[1] :

• Male: 20-50%
• Female: 15-50%

Higher transferrin saturation values are found in high iron states, such as megaloblastic anemia, sideroblastic anemia, and iron overload states. Decreased transferrin saturation values are found in chronic iron deficiency, chronic infection, extensive malignancy, tissue inflammation states, uremia, and nephrotic syndrome.

The value of the transferrin saturation is calculated with the formula below.

(Serum iron level X 100) / total iron-binding capacity

A normal transferrin saturation value is found in patients with normal iron levels.

Details for serum iron-binding capacity (IBC) evaluation are as follows:

• Specimen: Blood

• Container: Marble-top (serum separator tube [SST]) or red-top tube

• Collection method: Routine venipuncture of 6-10 mL

Details for serum iron evaluation are as follows:

• Specimen: Blood

• Container: Red-top tube

  Red-top tube for iron and iron-binding capacity values.

• Collection method: Routine venipuncture of 6-10 mL

Transferrin saturation calculation requires the serum iron and IBC values.

Iron tests (including ferritin, iron, transferrin, and IBC) are ideally drawn early in the morning, after a 12-hour fast, when serum iron values are highest. Diurnal variation exists, with iron values lowest in the evening.

Hemolysis during collection of blood specimens may invalidate the accuracy of iron tests.[2]

Iron tests may be less reliable if drawn within 4 days to 1 week of a blood transfusion[3] ; it is also possible that tests and treatments involving the use of radioactive materials can alter iron test results.

Medications should be noted, particularly if the patient is taking multivitamins with iron or oral contraceptives.

Panels

Transferrin saturation is typically part of the iron deficiency panel.

Description

The terms transferrin saturation and iron-binding capacity, saturation, are interchangeable; however, in the last several years, this value is most commonly referred to simply as the transferrin saturation. This also minimizes confusion with another frequently used value, the iron-binding capacity, when determining a patient’s iron status.

Iron-binding capacity

To measure the iron-binding capacity (IBC), a standard amount of exogenous iron is added to the patient’s serum in the laboratory. This iron occupies all of the available binding sites and may produce an excess of unbound iron. Then, a standard amount of magnesium carbonate is added, which binds to the unbound iron, forming iron-carbonate complexes.

The sample is centrifuged, removing iron-carbonate complexes, leaving unbound iron in the supernatant. Measurement of this unbound supernatant provides the value of the IBC.[4] This IBC value is therefore an indirect measure of protein transferrin, which binds iron in serum.

Other methods of IBC determination are based on the same principle of adsorbent methods, with charcoal, columns of alumina, or ion-exchange resins.[4]

Transferrin saturation

The transferrin saturation is calculated with the formula below.

(Serum iron level X 100) / total iron-binding capacity

Transferrin saturations of less than 20% indicate iron deficiency, while transferrin saturations of more than 50% suggest iron overload.

Iron tests frequently performed together to diagnose iron deficiency or overload include serum iron, ferritin, IBC, and transferrin levels.

Indications/Applications

The most common indication for obtaining a transferrin saturation level is to determine a patient’s iron status, either deficiency or overload.[5, 6]

The IBC value and transferrin saturation are best interpreted in the context of additional iron studies (typically, serum iron, ferritin, transferrin) and in the clinical context of the patient’s baseline health state.[7]

After iron repletion, the IBC value may be redrawn with other iron tests to assess therapy.

The IBC is a useful test in determining the stage of iron deficiency. For example, the earliest markers of iron deficiency include ferritin, marrow iron, and IBC. These are followed by serum iron, percentage of transferrin saturation, and decreases in hemoglobin and hematocrit.

In pediatric populations with anemia, a transferrin saturation of less than 16% is diagnostic of iron deficiency anemia. It is limited by diurnal variation in serum iron levels.[8]

A study by van der Staaij et al indicated that the ratio of transferrin saturation to hepcidin can be used to distinguish TMPRSS6-related iron refractory iron deficiency anemia from iron deficiency anemia arising from other causes, if inflammation is low or absent and no recent iron therapy has been administered. The investigators found the median transferrin saturation/hepcidin ratio to be higher for patients with the iron refractory anemia than for the other iron deficiency anemia cases, the values being 0.6%/nM and 16.7%/nM, respectively.[9]

Considerations

Medications that may increase IBC values include fluorides and birth control pills. Medications that can decrease IBC values include adrenocorticotropic hormone (ACTH) and chloramphenicol.

In states of iron overload, with resulting excess iron deposition in tissues, excess free iron can result in cirrhosis, diabetes, cardiomyopathy, arthritis, and other endocrine disorders;[10] thus, it is important to monitor iron tests, including IBC and transferrin saturation values.

Examples can be found throughout the literature of attempts to correlate a TIBC or transferrin saturation value to a particular disorder. For example, a recent retrospective study found that men with anemia should undergo a thorough endoscopic evaluation to assess for gastrointestinal neoplasms when the transferrin saturation value is 9% or less.[11] Further studies are needed to determine if IBC and transferrin saturation values may be diagnostic in other disorders.

Furthermore, investigators have also tried to establish goal values of transferrin saturation in particular disorders. For example, in patients with chronic kidney disease, the 2006 Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines recommend assessment of iron tests to determine the contribution of iron deficiency to anemia. The KDOQI recommends maintaining a transferrin saturation of 20% or more to ensure adequate supply of iron for erythropoiesis in patients on stimulating agents.[12]

With iron deficiency being a mortality risk factor in patients with heart failure, a study by Campodonico et al indicated that in persons hospitalized for worsening heart failure, the prognosis is poorer for those with transferrin saturation of less than 20%. The worst survival rate was among patients with a composite of transferrin saturation below 20% and a ferritin level of between 100 and 300 μg/L.[13]