Transferrin

Generality

Transferrin (Tf) is a plasma protein that carries iron in the blood.

Synthesized by the liver and the monocytic-macrophage system, transferrin is able to bind in a very stable but reversible way the iron coming from the degradation of red blood cells and the alimentary one absorbed in the intestine.

After binding it to itself, transferrin transports iron to the places of use (in particular the bone marrow) and deposit (in particular the liver).

Transferrin can be compared to a truck that continuously transports iron from deposits (ferritin) to the cells that need it, via the bloodstream.

From the structural point of view, transferrin is a glycoprotein formed by a polypeptide chain of 679 amino acids, with a molecular weight of about 80 KD and a half-life of about 8 days.

The dosage of transferrin in the blood ( transferrinemia ) evaluates the ability to transport iron. This examination is prescribed together with the analysis of serum iron and ferritin values, where anomalies of iron metabolism are suspected.

What's this

Transferrin is the main transport protein in the blood of oxidized iron (Fe3 +) .

It plays a key role in hematopoiesis, being responsible for the transfer of iron to cells (erythroblasts), which need them to synthesize heme (hemoglobin, myoglobin and cytochrome). Special membrane receptors bind to transferrin and the whole complex enters the cell by endocytosis; once the iron is removed, the transport protein is re-expanded in the plasma.

In the blood, transferrin can be found either in free form - not bound to iron ( unsaturated transferrin ), or in iron-bound form ( saturated transferrin ).

The latter share coincides with the sideremia value.

In clinical practice, the following parameters are measured:

• Sideremia : share of circulating transferrin saturated in iron;
• Transferrinemia : direct plasma transferrin dosage;
• Total ability to bind iron (TIBC) : indirect measure of the ability of transferrin to bind iron.

Transferrin saturation

Although iron associated with transferrin is less than 0.1% of total body iron, this percentage represents the most dynamically important fraction, characterized by a high turnover rate (25 mg / 24 h).

Transferrin can bind to itself two Fe3 + iron atoms at the level of two different molecular sites:

• When this carrier protein is free of these bonds it is called apotransferrin ;
• When it binds the atoms of the metal it is called saturated transferrin .

The bond with the iron atom is possible only when there is a concomitant anionic bond with a bicarbonate molecule which, unlike the metal one, is particularly weak.

Under normal conditions, plasma transferrin is saturated with trivalent iron for about 30%; in the plasma we can therefore distinguish different forms:

• the one without iron (apotransferrin),
• the completely saturated (diferric transferrin)
• that which contains iron only at the C-terminal site or in the N-terminal site (monomeric transferrin).

The total capacity of binding iron or TIBC (Total Iron Binding Capacity) is defined as the ability of plasma proteins to bind iron.

Since transferrin is the main protein with metal binding capacity, TIBC values ​​can be established to determine plasma transferrin levels (among other things less expensive than direct determination).

The normal TIBC values ​​vary between 240 and 450 μg / dL (43.0-80.6 μmol / L)

The ratio between sideremia and total iron binding capacity defines the saturation of transferrin, a figure usually expressed as a percentage.

Saturation of transferrin = (sideremia / TIBC) x 100

Normal values ​​for men: 20-50%

Normal woman values: 15-50%

Sideremia measures the amount of transport iron present in the blood.

The UIBC expresses the reserve capacity of transferrin, that is to say the protein fraction which has not yet been saturated with iron; this haematochemical parameter can be calculated directly or through the formula: TIBC - sideremia.

The circulating iron in the plasma is transferred to the cells through the binding of transferrin with its receptor (TfR). The affinity for this receptor (a transmembrane glycoprotein of 180 kD molecular weight) is maximum for diferric transferrin, intermediate for the monophrenic and minimum for apotransferrin. The transfer of the metal to the cells takes place mainly through the diferric transferrin.

The expression of transferrin receptors at the level of bone marrow erythroid cells increases with increasing values ​​of circulating erythropoietin. Hence the usefulness of monitoring soluble transferrin receptor levels to identify athletes who use EPO.

Why do you measure

The dosage of transferrin in the blood (transferrinemia) serves to determine the body's ability to transport iron. Furthermore, the examination can help in monitoring liver function and to assess an individual's nutritional status.

The transferrin dosage is not part of the routine tests, but is prescribed when the first symptoms of an accumulation or, more commonly, of an iron deficiency appear, whatever the triggering cause (hemochromatosis, hemosiderosi, anemias etc.).

In any case, the value of transferrin is generally evaluated together with sideremia and ferritin to get a more complete picture of iron metabolism .

Note

Although transferrinemia and TIBC are two different exams, they have an overlapping trend and essentially the same clinical significance. Therefore, at the discretion of the doctor, it may be sufficient to carry out only one of the two exams.

Normal values

The normal values ​​of transferrin (transferrinemia) range from 240 to 360 mg / dL.

The dosage of transferrin is generally prescribed together with that of sideremia and ferritin, in subjects in whom abnormalities of iron metabolism are suspected.

High transferrin - Causes

An increase in serum transferrin concentrations (hypertransferrinemia) occurs in all those situations that require an increased need for iron, for example in the presence of:

• Bleeding (including occult bleeding);
• Sideropenic anemias;
• During growth and pregnancy;
• Hypoxemic states.

Transferrin levels may increase following the use of hormonal contraceptives. Increases in values ​​are also typical in the third trimester of pregnancy and in children between two and ten years.

Low transferrin - Causes

A reduction in serum transferrin concentrations (hypotransferrinemia) occurs in the event of:

• Malnutrition, cachexia and protein deficiencies;
• Liver disease (such as cirrhosis, hepatitis, liver failure) or kidney (due to loss of protein with urine);
• Acute and chronic inflammatory states;
• hemochromatosis;
• Repeated transfusions and martial overload (the concentration of transferrin in the plasma varies inversely with the level of reserves; on the contrary, transferrin saturation decreases in iron deficiencies and increases in excesses).

Decreases in transferrin may be observed during therapy with chloramphenicol or ACTH.

A near-total absence of transferrin (<10 mg / dL) is typical of an extremely rare autosomal recessive disease called atransferrinemia.

How to measure it

To carry out the transferrin test, the patient must undergo a blood test .

Preparation

Venous blood is usually taken in the morning . Before undergoing the examination, the patient must observe a fast of at least 8 hours. During this period, a small amount of water can be taken. Furthermore, suspension of iron supplements is recommended for the two days preceding the analysis.

Interpretation of Results

• Low transferrin (hypotransferrinemia) may lead to suspicion of iron overload, as occurs following repeated transfusions or hemochromatosis. Reduced values ​​can also be found due to the presence of anemia caused by chronic inflammatory infections and diseases, malnutrition, liver cirrhosis or nephrotic syndrome. A lowering of the values ​​is also observable due to the intake of the hormone ACTH and the antibiotic chloramphenicol or during the use of cortisone.
• High transferrin (hypertransferrinemia) generally indicates a deficiency or greater need for iron, as in the case of bleeding, iron deficiency anemia or hypoxemia. Oral contraceptives can also lead to increased transferrinemia.

However, it should be reiterated that this examination must be interpreted in an overall view of the tests concerning iron metabolism in the body. For example, in iron deficiency anemia (ie from iron deficiency), an initial reduction in ferritin is observed, followed by an increase in total iron-binding capacity and a reduction in sideremia.