Fibrin is a protein involved in the clotting of blood. It is a fibrillar protein that is polymerised to form a "mesh" that forms a haemostatic plug or clot (in conjunction with platelets) over a wound site.
Fibrin is made from its zymogen 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.
Fibrin generation
Fibrinogen is a 340-KD glycoprotein synthesised in the liver hepatocytes and megakaryocytes, which normally has a concentration between 1.5 - 4.0 g/L (normally measured using the Clauss method) in blood plasma. 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 ). Herditary abnormalities of fibrinogen (the gene is carried on chromosome 4) are of both quantitative and quualitative in nature and include; afibrinogenaemia , hypofibrinogenaemia , dysfibrinogenaemia , and hypodysfibrinogenaemia . In its natural form, fibrinogen is useful in forming bridges between platelets, by binding to their GpIIb/IIIa surface membrane proteins; though fibrinogen's major use is as a precursor to fibrin.
Fibrinogen is a symmetrical dimer composed of 6 paired polypeptide chains. (alpha, beta, and gamma chains). 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.
Following the activation of prothrombin to thrombin (Factor IIa). Thrombin cleaves fibrinopeptide A off the alpha chain and reveals a site in the E domain that can bind to the carboxy terminal end of the gamma chain. Beta chain cleavage occurs more slowly and contributes to the fibril and fiber associations of fibrinogen. These processes convert fibrinogen to fibrin.
The active molecules of fibrin stack up on each other, usually incorporating (by trapping) aggregrates of platelets and molecules of thrombin. The soluble fibrin molecules are later cross-linked (by factor XIII) with covalent bonds, to form a stable hemostatic plug, thus effectively stopping bleeding.
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