Transferrin Saturation - Causes and Clinical Diagnosis

Introduction

Iron is a very important nutritional requirement. It is an essential component in red blood cells and is required to perform various biological functions such as oxygen transport. Its levels in the blood are critically regulated, and any alteration in iron homeostasis (either increase or decrease) causes harm to the body. Low levels of iron in the blood have been reported as the most commonly existing global nutritional deficiencies leading to anemias. Whereas, high levels of iron get deposited in several organs resulting in toxic effects.

Transferrin is a specialized iron-binding protein that acts as a vehicle for iron transport in the blood. It functions as the prime iron pool of the body. Transferrin transports iron to various organs (liver, bone marrow, and spleen). Its saturation levels (maximum iron carrying capacity) serve as an essential indicator of iron status in the body which is used for diagnostic purposes.

What Is Transferrin?

Transferrin is the transport form of iron in plasma (the liquid part of the blood). It is a glycoprotein that is responsible for iron transport in the body and plays an essential role in iron metabolism. Some of the essential functions of transferrin are as follows -

• Transferrin has a high affinity (greater attraction) for ferric iron (Fe3+) and binds with two iron atoms (absorbed from dietary iron intake) in the plasma.

• It transports iron to various tissues for different metabolic activities.

• The majority of the transferrin-bound iron is supplied to the bone marrow, liver, and spleen.

• The liver synthesizes transferrin and its production is regulated by iron stores in the body.

• When iron stores in the body reduce (anemia), more transferrin is produced from the liver as a counter-feedback regulation.

• Serum transferrin levels help to assess the iron status in the body.

• It plays an essential role in detecting disorders that affect iron metabolism in the body.

• In normal health, the plasma transferrin level is 2.0 g/l to 3.0 g/l, where 1 mg of transferrin binds to 1.4 micrograms of iron.

• Plasma transferrin levels also reflect the protein status of the body.

What Is Meant by Transferrin Saturation?

Transferrin saturation (TSAT) refers to the maximum capacity of a transferrin molecule to hold or bind with plasma iron. It is also known as total iron-binding capacity or transferrin iron binding capacity (TIBC).

• The normal reference range in adults is 250 μg/dL to 400 μg/dL.

• Transferrin saturation is also expressed in percentage. The plasma transferrin saturation percentage is estimated by dividing the total serum iron level by TIBC.

• The normal reference range for serum transferrin saturation is 15 to 50 percent.

• Hypertransferrinemia results from increased TIBC.

• Hypotransferrinemia occurs due to reduced transferrin saturation levels.

When Is Transferrin Saturation Elevated?

Elevated serum transferrin saturation levels commonly occur due to increased iron overload in the blood. These increased iron levels in plasma are caused by excessive absorption of dietary iron from the intestines which is associated with various reasons such as genetic causes, racial and ethnic predisposition, or metabolic abnormalities. Excessive iron in plasma eventually results in increased deposition of iron in cells and tissues.

Some of the causes for elevated transferrin saturation (TSAT) are as follows -

• Hemochromatosis (increased accumulation of iron due to genetic defects).

• Iron-loading anemias (sideroblastic anemia, congenital dyserythropoietic anemia).

• Megaloblastic anemia.

• Acute iron deficiencies (in case of massive blood loss).

• Pregnancy (increased demand for iron).

• Hereditary iron overloads such as African iron overload.

• Drug-induced (administration of oral contraceptives).

When Is Transferrin Saturation Decreased?

Low levels of transferrin are often associated with conditions that affect protein metabolism in the body. The presence of infections, inflammatory disorders, and chronic diseases reduces the production of transferrin molecules. It is also seen in anemic conditions due to iron deficiency over a longer duration of time. Reduced transferrin saturation occurs in the following conditions -

• Hypoalbuminemia (severe protein malnutrition).

• Nephrotic syndrome (loss of proteins through kidneys).

• Chronic iron deficiency anemia (reduced body iron stores for a very long time).

• Chronic infections.

• Severe forms of malignancies.

• Inflammatory disorders.

• Uremia.

How Is the Transferrin Saturation Test Done?

Transferrin saturation test is a simple test that requires a blood sample of the individual. Following procedures are followed to achieve accurate TSAT values.

• Blood is drawn from a vein in the arm using a sterile needle.

• No preparation is needed prior to giving the blood sample.

• serum iron levels commonly show diurnal (more active in the daytime) fluctuations and also change according to dietary intake of iron.

• Hence the recommended timing for the transferrin saturation test is fasting early morning sample.

• This considerably reduces the diurnal variations in the values of TSAT.

• The presence of infection or chronic disease lowers TSAT values.

• Transferrin saturation alone does not assess the iron status of the body. Its evaluation is not interpreted in isolation.

• It is included in the panel of iron estimation tests and is always done in combination with other laboratory tests such as serum iron concentration, ferritin (storage form of iron) level, and iron binding capacity (IBC).

How Does Transferrin Saturation Help in Clinical Diagnosis?

• Less than 16 % of transferrin saturation (TSAT) indicates an insufficient supply of iron for erythropoiesis (production of red blood cells), thereby leading to the development of iron deficiency anemia.

• The most significant use of TSAT levels is in diagnosing hereditary hemochromatosis.

• Increased overload of iron even in the initial stages of hemochromatosis is easily detected by TSAT levels.

• A threshold of more than 50 percent transferrin saturation is indicative of hemochromatosis in males and for females, it is greater than 45 percent.

• Excessive accumulation of iron in organs like the liver, heart, pancreas, and brain leads to tissue damage resulting in diseases such as cirrhosis, cardiac failure, diabetes, and cerebral stroke, respectively.

• Increased iron overload leading to comorbid conditions such as cirrhosis and heart failure is often detected by an elevated transferrin saturation (TSAT).

• The mortality risk significantly increases with TSAT levels of more than 60 percent.

Conclusion

Iron is an essential element for diverse metabolic and physiological processes. Transferrin is a protein that binds with iron and carries it to the required biological sites. An imbalance in iron metabolism in the body causes various disorders. Assessment of transferrin saturation is considered the most efficient tool for assessing disorders associated with iron stores such as hemochromatosis, iron deficiency anemias, and other conditions related to iron overloads.