Everything about Fibrinogen totally explained
Fibrin is a
protein involved in the clotting of blood. It is a fibrillar protein that's
polymerised to form a "mesh" that forms a
hemostatic plug or clot (in conjunction with
platelets) over a wound site.
Fibrin is made from its
zymogen fibrinogen, a soluble
plasma glycoprotein that's synthesised by the
liver. Processes in the
coagulation cascade activate the zymogen
prothrombin to the
serine protease thrombin, which is responsible for converting fibrinogen into fibrin. Fibrin is then cross linked by
factor XIII to form a clot. Recent research has shown that fibrin plays a key role in the inflammatory response and development of rheumatoid arthritis.
Physiology
Fibrinogen (also called factor I) is a 340 kDa glycoprotein synthesised in the liver by hepatocytes and megakaryocytes. The concentration in blood plasma is 1.5 - 4.0 g/L (normally measured using the Clauss method) or about 7 µM. In its natural form, fibrinogen can form bridges between platelets, by binding to their GpIIb/IIIa surface membrane proteins; however its major function is as the precursor to fibrin.
Fibrinogen, the principal protein of vertebrate blood clotting, is an hexamer containing two sets of three different chains (α, β, and γ), linked to each other by disulfide bonds. The N-terminal sections of these three chains are evolutionary related and contain the cysteines that participate in the cross-linking of the chains. However, there's no similarity between the C-terminal part of the α chain and that of the β and γ chains. The C-terminal part of the β and γ chains forms a domain of about 270 amino-acid residues. This domain contains four conserved cysteines involved in two disulfide bonds. On the alpha and beta chains, there's a small peptide sequence (called a fibrinopeptide). It is these small peptides that prevent fibrinogen spontaneously forming polymers with itself.
- Fibrinogen (External Link
) beta and gamma chains C-terminal domain signature
Role in disease
Excessive generation of fibrin due to activation of the coagulation cascade leads to
thrombosis, while ineffective generation predisposes to
hemorrhage.
Dysfunction or disease of the liver can lead to a decrease in fibrinogen production or the production of abnormal fibrinogen molecules with reduced activity (
dysfibrinogenaemia). Hereditary abnormalities of fibrinogen (the gene is carried on chromosome 4) are of both quantitative and qualitative in nature and include;
afibrinogenaemia,
hypofibrinogenaemia,
dysfibrinogenaemia, and
hypodysfibrinogenaemia.
Diagnostic use
Fibrinogen levels can be measured in
venous blood. Normal levels are about 150-300 mg/dL. Higher levels are, amongst others, associated with
cardiovascular disease (>460 mg/dL). It may be elevated in any form of
inflammation, as it's an
acute phase protein.
It is used in
veterinary medicine as an inflammatory marker: in horses a level above the normal range of 1.0-4.0 g/L suggests some degree of systemic inflammatory response.
Low levels of fibrinogen can indicate a systemic activation of the clotting system, with consumption of clotting factors faster than synthesis. This excessive clotting factor consumption condition is known as Disseminated Intravascular Coagulation or "DIC." DIC can be difficult to diagnose, but a strong clue is low fibrinogen levels in the setting of prolonged clotting times (PT or PTT), in the context of acute critical illness such as sepsis or trauma.
Further Information
Get more info on 'Fibrinogen'.
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