Fibrin is a fibrous, non-globular protein involved in the clotting of blood. It is formed by the action of the protease thrombin on fibrinogen, which causes it to polymerize. The polymerized fibrin, together with platelets, forms a hemostatic plug or clot over a wound site.
Fibrinogen is a glycoprotein complex, produced in the liver, that circulates in the blood of all vertebrates. During tissue and vascular injury, it is converted enzymatically by thrombin to fibrin and then to a fibrin-based blood clot. Fibrin clots function primarily to occlude blood vessels to stop bleeding. Fibrin also binds and reduces the activity of thrombin. This activity, sometimes referred to as antithrombin I, limits clotting. Fibrin also mediates blood platelet and endothelial cell spreading, tissue fibroblast proliferation, capillary tube formation, and angiogenesis and thereby promotes revascularization and wound healing.
Thrombin is a serine protease, an enzyme that, in humans, is encoded by the F2 gene. During the clotting process, prothrombin is proteolytically cleaved by the prothrombinase enzyme complex to form thrombin. Thrombin in turn acts as a serine protease that converts soluble fibrinogen into insoluble strands of fibrin, as well as catalyzing many other coagulation-related reactions.
Tissue factor, also called platelet tissue factor, factor III, or CD142, is a protein encoded by the F3 gene, present in subendothelial tissue and leukocytes. Its role in the clotting process is the initiation of thrombin formation from the zymogen prothrombin. Thromboplastin defines the cascade that leads to the activation of factor X—the tissue factor pathway. In doing so, it has replaced the previously named extrinsic pathway in order to eliminate ambiguity.
Integrin beta-3 (β3) or CD61 is a protein that in humans is encoded by the ITGB3 gene. CD61 is a cluster of differentiation found on thrombocytes.
The dysfibrinogenemias consist of three types of fibrinogen disorders in which a critical blood clotting factor, fibrinogen, circulates at normal levels but is dysfunctional. Congenital dysfibrinogenemia is an inherited disorder in which one of the parental genes produces an abnormal fibrinogen. This fibrinogen interferes with normal blood clotting and/or lysis of blood clots. The condition therefore may cause pathological bleeding and/or thrombosis. Acquired dysfibrinogenemia is a non-hereditary disorder in which fibrinogen is dysfunctional due to the presence of liver disease, autoimmune disease, a plasma cell dyscrasias, or certain cancers. It is associated primarily with pathological bleeding. Hereditary fibrinogen Aα-Chain amyloidosis is a sub-category of congenital dysfibrinogenemia in which the dysfunctional fibrinogen does not cause bleeding or thrombosis but rather gradually accumulates in, and disrupts the function of, the kidney.
Integrin alpha-IIb is a protein that in humans is encoded by the ITGA2B gene. ITGA2B, also known as CD41, encodes integrin alpha chain 2b. Integrins are heterodimeric integral membrane proteins composed of an alpha chain and a beta chain. Alpha chain 2b undergoes post-translational cleavage to yield disulfide-linked light and heavy chains that join with beta 3 to form a fibrinogen receptor expressed in platelets that plays a crucial role in coagulation. Mutations that interfere with this role result in thrombasthenia. At least 38 disease-causing mutations in this gene have been discovered. In addition to adhesion, integrins are known to participate in cell-surface mediated signalling.
Coagulation factor XIII A chain is a protein that in humans is encoded by the F13A1 gene.
Coagulation factor XIII B chain is a protein that in humans is encoded by the F13B gene.
Fibrinogen alpha chain is a protein that in humans is encoded by the FGA gene.
Fibrinogen beta chain, also known as FGB, is a gene found in humans and most other vertebrates with a similar system of blood coagulation.
Protease-activated receptor 4 (PAR-4), also known as coagulation factor II (thrombin) receptor-like 3, is a protein that in humans is encoded by the F2RL3 gene.
Endothelial protein C receptor (EPCR) also known as activated protein C receptor is a protein that in humans is encoded by the PROCR gene. PROCR has also recently been designated CD201.
Laminin subunit gamma-2 is a protein that in humans is encoded by the LAMC2 gene.
Hyaluronan-binding protein 2 also known as factor VII activating protease (FSAP) is a protein that in humans is encoded by the HABP2 gene.
Fibrinogen-like protein 2, also known as FGL2, is a protein which in humans is encoded by the FGL2 gene.
Fibrinogen-like protein 1 (FGL-1) is a protein that is structurally related to fibrinogen. In humans, FGL-1 is encoded by the FGL1 gene. Four splice variants exist for this gene.
Laminin subunit gamma-3 also known as LAMC3 is a protein that in humans is encoded by the LAMC3 gene.
Hypodysfibrinogenemia, also termed congenital hypodysfibrinogenemia, is a rare hereditary fibrinogen disorder cause by mutations in one or more of the genes that encode a factor critical for blood clotting, fibrinogen. These mutations result in the production and circulation at reduced levels of fibrinogen at least some of which is dysfunctional. Hypodysfibrinogenemia exhibits reduced penetrance, i.e. only some family members with the mutated gene develop symptoms.
Congenital hypofibrinogenemia is a rare disorder in which one of the three genes responsible for producing fibrinogen, a critical blood clotting factor, is unable to make a functional fibrinogen glycoprotein because of an inherited mutation. In consequence, liver cells, the normal site of fibrinogen production, make small amounts of this critical coagulation protein, blood levels of fibrinogen are low, and individuals with the disorder may develop a coagulopathy, i.e. a diathesis or propensity to experience episodes of abnormal bleeding. However, individuals with congenital hypofibrinogenemia may also have episodes of abnormal blood clot formation, i.e. thrombosis. This seemingly paradoxical propensity to develop thrombosis in a disorder causing a decrease in a critical protein for blood clotting may be due to the function of fibrin to promote the lysis or disintegration of blood clots. Lower levels of fibrin may reduce the lysis of early fibrin strand depositions and thereby allow these depositions to develop into clots.
