Fibrinogen

Fibrinogen (Factor I), was discovered by Dennis de Commercy and Olof Hammarsten. Fibrinogen is a glycoprotein, a substrate of thrombin, which cleaves fibrinomers from fibrinogen. It belongs to the group of acute phase proteins and is synthesized in the liver. The molecular weight is 340 kD and consists of two sets of three covalently bound polypeptide chains.

Platelet activation leads to a structural change in the integrin receptor, which can then bind fibrinogen with high affinity. The result is cross-linking of platelets by fibrinogen. This can be the initial trigger for the generation of a thrombus.

Fibrinogen is present in the blood in a dissolved form. When a tissue is injured, a cascade process of activation of the procoagulant factors circulating in the plasma is triggered, which takes place on the surface of the activated platelets. This gives rise to the enzyme thrombin from its precursor prothrombin. Thrombin(factor II) sequentially cleaves fibrinopeptides A (fibrinopeptide-A) and B (fibrinopeptide-B) from the A-alpha--and B-beta chains of the protein complex. The fibrin monomers thus released polymerize spontaneously to form water-insoluble fibrin. Further crosslinking by factor XIIIa results in a stable thrombus.

The plasma concentration of fibrin is 160-350 mg/dl. The fibrin concentration is lower in the lymphatic fluid. The half-life of fibrin is three to five days.

The fibrinogen is elevated as an acute phase protein in acute and chronic inflammation, pregnancy, tumours and occlusive diseases. It is decreased in liver damage, in the context of a consumption coagulopathy or under fibrinolytic therapy.
The fibrin cleavage products polymerize to fibrin, which joins the platelets to a thrombus by attaching them to their GPIIb-/ GPIIIa receptors.

It has long been known that increased fibrinogen levels are a risk factor for the development of arteriosclerotic changes. Fibrinogen correlates with other risk factors such as coronary heart disease, obesity, nicotine, diabetes and cholesterol. Pre-menopausal women and women who take hormonal anti-conception drugs have increased fibrinogen levels.

Regular physical exercise can significantly reduce an elevated fibrinogen level and thus significantly reduce the risk of developing arteriosclerosis. People with low fibrinogen concentrations have a significantly lower risk of developing conorrheal disease, even if they have elevated serum cholesterol.

Standard value: The standard value is 150 to 400 mg/dl; 4.8 - 12.0 µmol/l

Pathologically decreased: cachexia, medimant, hyperfibrinolysis, congenital A-, hypo- and dysfibrinogenemias, severe liver parenchyma damage, consumption and loss coagulopathy

Pathologically increased: nephrotic syndrome, infections, inflammatory and rheumatic diseases, malignant tumours, necrosis and tissue damage

Fibrinogen is the product of three closely linked genes:

• FGA gene
• FGB gene
• FGG gene

The fibrinogen genes are located on human chromosome 4 (and are translated into nascent polypeptides of the pre-Pro-Aα chain (644 amino acid residues), the pre-Pro-Bβ chain (491 residues), and the pre-Pro-γ chain (437 residues).

Extension of the open reading frame into an alternatively spliced sixth intron results in 1-2% of molecules in adult blood having a longer Aα chain (αE), such that they contain an additional domain homologous to the C-terminal Bβ and γ chains, resulting in a fibrinogen molecule with a molecular mass of 420 kDa, compared with 340 kDa for the main fibrinogen fraction with the shorter Aα chains.

Alternative splicing of the γ-chain mRNA results in 8-15% of plasma fibrinogen molecules in which the C-terminal 400-411 dodecapeptide of the γ-chain (γA-chain) is altered by addition of new amino acids from 408 to 427 (γ′-chain).

1. HA Neumann (2014) The coagulation system. ABW-Wissenschaftsverlag GmbH Berlin S. 49f.