FIBRINOGEN: FUNCTION, HIGH AND LOW CONCENTRATIONS, NORMAL VALUES - BIOLOGY - 2025

The Fibrinogen is a plasma glycoprotein that, being cut by an enzyme known as thrombin is transformed into fibrin, one of the most abundant protein components forming blood clots (one of the 13 factors involved in blood clotting).

It is a large protein, weighing approximately 340 kDa and is made up of two symmetric molecular “building blocks”, each one made up of three different polymorphic polypeptide chains known as Aα, Bβ and γ, which are covalently linked to each other. through 29 disulfide bridges.

Structural scheme of human fibrinogen (Source: 5-HT2AR via Wikimedia Commons)

Structurally, in fibrinogen three domains or regions can be distinguished: two terminal domains called "D domains" and a central domain called "E domain". The central domain is linked on each side to a D domain thanks to an array of polypeptides.

Each of the three types of chains that make up this protein is produced in the liver from the expression of three different genes, all of which are found on chromosome number 4 in humans.

Fibrinogen function

Hemostasis (prevention of blood loss)

Fibrinogen is the precursor protein of a polypeptide known as fibrin, which is one of the main components of blood clots in mammals, which is why it is said to be actively involved in the maintenance of hemostasis.

In places where the body suffers some kind of injury or injury, fibrinogen is cut by a protein with proteolytic activity known as α-thrombin. The cut releases, from the N-terminal ends of the Aα and Bβ chains, two fibrinopeptides called fibrinopeptide A and fibrinopeptide B.

Both peptides can spontaneously polymerize and cross-link to form a clot or a transient fibrin matrix, essential for preventing blood loss and for normal tissue repair, which occurs at the end of the coagulation cascade.

This matrix can be further degraded by plasmin or by other proteases such as elastase, tryptase and some cathepsins.

Avoid blood loss

In addition to the formation of fibrin networks, fibrinogen can also prevent blood loss by acting as an adhesive protein, promoting platelet aggregation or serving as an initial scaffold for clot formation.

Tissue repair

Fibrinogen proteolysis products have also been recognized as promoters of events of great importance for tissue repair such as vasoconstriction, angiogenesis, directed cell migration and proliferation of cells such as fibroblasts, some muscle cells smooth and lymphocytes.

High blood concentrations (meaning)

When inflammatory processes are triggered in the body, liver cells show a drastic increase in the expression and synthesis of fibrinogen, which is thought to be controlled by factors such as interleukin-6 (IL-6), some glucocorticoids and oncostatin M.

Fibrin protein formed from fibrinogen

For this reason, high plasma values ​​of this protein can indicate the presence of infections, cancers, inflammatory disorders, trauma, among others.

There is growing evidence now to suggest that high blood fibrinogen concentrations may also be associated with an increased risk of cardiovascular disorders, including:

- Ischemic heart disease (IHD)

- Heart attacks and cardiovascular accidents

- Thromboembolism (formation of clots inside a blood vessel)

The increase in plasma fibrinogen can promote a “prothrombotic” or “hyper coagulated” state, as there is greater availability of this protein to be processed and contribute to the production of clots without the existence of any trauma, in addition to producing a greater amount of protein from which it can be processed.

Among the factors that influence the increase in plasma fibrinogen content are, in addition, the progress of age, body mass index, cigarette addiction, diabetes and post-menopausal states in women.

It is also related to fasting insulin, low-density lipoprotein (LDL) cholesterol, and white blood cell count, but is inversely related to moderate alcohol consumption, physical activity, and hormone replacement therapy.

Low blood concentrations (meaning)

A low concentration or deficiency of fibrinogen in the blood can be caused by three different pathological conditions: afibrinogenemia, hypofibrinogenemia, and dysfibrinogenemia.

The first of the three is related to the complete absence of fibrinogen in the plasma and can mean lethal risks of blood loss after an injury, so it can be a very dangerous condition.

Afibrinogenemia

Afibrinogenemia can also present venous and arterial thromboses through thrombin-mediated platelet activation. In women, this pathology causes 50% of the cases of menorrhagia (abundant menstrual bleeding) and pregnant women with afibrinogenemia have a higher risk of presenting severe obstetric complications.

Hypofibrinogenemia

Hypofibrinogenemia, on the other hand, has to do with abnormally low levels of this protein, that is, concentrations between 0.2 and 0.8 g / L. It is a basically asymptomatic condition, although it can also trigger heavy bleeding.

Patients with this condition may suffer from a disease known as fibrinogen storage disease, which is due to the accumulation of fibrinogen aggregates in the endoplasmic reticulum of fibrinogen-producing hepatocytes.

Dysfibrinogenemia

Lastly, dysfibrinogenemia is a condition of normal fibrinogen levels that does not function properly and, instead of bleeding, has been related to risks of thrombosis.

Additionally, chronic or persistent fibrinogen deficiency over time may be related to some acquired conditions such as the final stage of some liver disease or severe malnutrition.

Normal fibrinogen values

Fibrinogen, as already mentioned, is synthesized in liver cells (hepatocytes), its half-life is more or less 100h and its normal concentration in blood plasma, together with other circulating components, is around 9 micromoles per liter, which represents around 1.5 and 4.5 g / L.

This concentration, however, exceeds the minimum concentration necessary for the maintenance of hemostasis, which is between 0.5 and 1 g / L.

References

1. Herrick, S., Blanc-Brude, O., Gray, A., & Laurent, G. (1999). Fibrinogen. The international journal of biochemistry & cell biology, 31 (7), 741-746.
2. Kamath, S., & Lip, GYH (2003). Fibrinogen: biochemistry, epidemiology and determinants. Qjm, 96 (10), 711-729.
3. Lowe, GD, Rumley, A., & Mackie, IJ (2004). Fibrinogen plasma. Annals of clinical biochemistry, 41 (6), 430-440.
4. Mosesson, MW (2005). Fibrinogen and fibrin structure and functions. Journal of Thrombosis and Haemostasis, 3 (8), 1894-1904.
5. Mosesson, MW, Siebenlist, KR, & Meh, DA (2001). The structure and biological features of fibrinogen and fibrin. Annals of the New York Academy of Sciences, 936 (1), 11-30.
6. Murray, RK, Granner, DK, Mayes, PA, & Rodwell, VW (2014). Harper's illustrated biochemistry. Mcgraw-hill.
7. Neerman-Arbez, M., & Casini, A. (2018). Clinical Consequences and Molecular Bases of Low Fibrinogen Levels. International journal of molecular sciences, 19 (1), 192. doi: 10.3390 / ijms19010192
8. Stone, MC, & Thorp, JM (1985). Plasma fibrinogen-a major coronary risk factor. JR Coll Gen Pract, 35 (281), 565-569.