Fibrin (also called Factor Ia) is a protein involved in the clotting of blood. It is a fibrillar protein that is polymerised to form a "mesh" that forms a hemostatic plug or clot (in conjunction with platelets) over a wound site.

Fibrin is made from fibrinogen, a soluble plasma glycoprotein that is 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 (?, ?, and ?), 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 is no similarity between the C-terminal part of the ? chain and that of the ? and ? chains. The C-terminal part of the ? and ? 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 is a small peptide sequence (called a fibrinopeptide). It is these small peptides that prevent fibrinogen spontaneously forming polymers with itself.

• Fibrinogen http://www.expasy.org/prosite/PDOC00445 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 is 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.

See also

• Fibrinogen alpha chain
• Fibrinogen beta chain
• Fibrinogen gamma chain
• Fibrinolysis
• D-dimer

External links

• Defibrinated blood harvested from sheep video

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