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Fibrinogen

Fibrinogen (coagulation factor I) is a glycoprotein complex, produced in the liver,[1] that circulates in the blood of all vertebrates.[2] 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.[1] Fibrin also mediates blood platelet and endothelial cell spreading, tissue fibroblast proliferation, capillary tube formation, and angiogenesis and thereby promotes revascularization and wound healing.[3]

Reduced and/or dysfunctional fibrinogens occur in various congenital and acquired human fibrinogen-related disorders. These disorders represent a group of rare conditions in which individuals may present with severe episodes of pathological bleeding and thrombosis; these conditions are treated by supplementing blood fibrinogen levels and inhibiting blood clotting, respectively.[4][5] These disorders may also be the cause of certain liver and kidney diseases.[1]


Fibrinogen is a "positive" acute-phase protein, i.e. its blood levels rise in response to systemic inflammation, tissue injury, and certain other events. It is also elevated in various cancers. Elevated levels of fibrinogen in inflammation as well as cancer and other conditions have been suggested to be the cause of thrombosis and vascular injury that accompanies these conditions.[6][7]

Blood clotting is measured using standard tests, e.g. , partial thromboplastin time, thrombin time, and/or reptilase time. Low fibrinogen levels and dysfunctional fibrinogens usually prolong these times, whereas the lack of fibrinogen (i.e. afibrinogenemia) renders these times infinitely prolonged.

prothrombin time

Fibrinogen levels are measured in the isolated from venous blood by immunoassays, or through clotting assays such as the Clauss fibrinogen assay or prothrombin based methods.[31] Normal levels being about 1.5-3 g/L, depending on the method used. These levels are normal in dysfibrinogenemia (i.e. 1.5-3 g/L), decreased in hypofibrinogenemia and hypodysfibrinogenemia (i.e. <1.5 g/L), and absent (i.e. <0.02 g/L) in afibrinogenemia.

plasma

Functional levels of fibrinogen are measured on plasma induced to clot. The levels of clotted fibrinogen in this test should be decreased in hypofibrinogenemia, hypodysfibrinogenemia, and dysfibrinogenemia and undetectable in afibrinogenemia.

Functional fibrinogen/antigenic fibrinogen levels are <0.7 g/L in hypofibrinogenemia, hypodysfibrinogenemia, and dysfibrogenemia, and not applicable in afibrinogenemia.

Fibrinogen analysis can also be tested on whole-blood samples by thromboelastometry. This analysis investigates the interaction of coagulation factors, their inhibitors, anticoagulant drugs, and blood cells (specifically, platelets), during clotting and subsequent fibrinolysis as it occurs in whole blood. The test provides information on hemostatic efficacy and maximum clot firmness to give additional information on fibrin-platelet interactions and the rate of fibrinolysis (see ).

Thromboelastometry

Scanning electron microscopy and confocal laser scanning microscopy of in vitro-formed clots can give information on fibrin clot density and architecture.

The or fibrinogen scan was formerly used to detect deep vein thrombosis. In this method, radioactively labeled fibrinogen, typically with radioiodine, is given to individuals, incorporated into a thrombus, and detected by scintigraphy.

fibrinogen uptake test

Clinical analyses of the fibrinogen disorders typically measure blood clotting using the following successive steps:[28] Higher levels are, amongst others, associated with cardiovascular disease (>3.43 g/L). It may be elevated in any form of inflammation, as it is an acute-phase protein; for example, it is especially apparent in human gingival tissue during the initial phase of periodontal disease.[29][30]

Hyperfibrinogenemia[edit]

Levels of functionally normal fibrinogen increase in pregnancy to an average of 4.5 gram/liter (g/L) compared to an average of 3 g/L in non-pregnant people. They may also increase in various forms of cancer, particularly gastric, lung, prostate, and ovarian cancers. In these cases, the hyperfibrinogenemia may contribute to the development of pathological thrombosis. A particular pattern of migratory superficial vein thrombosis, termed trousseau's syndrome, occurs in, and may precede all other signs and symptoms of, these cancers.[7][32] Hyperfibrinogenemia has also been linked as a cause of persistent pulmonary hypertension of the newborn[33] and post-operative thrombosis.[34] High fibrinogen levels had been proposed as a predictor of hemorrhagic complications during catheter-directed thrombolysis for acute or subacute peripheral native artery and arterial bypass occlusions.[35] However, a systematic review of the available literature until January 2016 found that the predictive value of plasma fibrinogen level for predicting hemorrhagic complications after catheter-directed thrombolysis is unproven.[36]

History[edit]

Paul Morawitz in 1905 described fibrinogen.[37]

Jennifer McDowall/Interpro:

Protein of the Month: Fibrinogen.

Peter D'Eustachio/reactome:

fibrinogen → fibrin monomer + 2 fibrinopeptide A + 2 fibrinopeptide B

Khan Academy Medicine (on YouTube):

Clotting 1 - How do we make blood clots?

Overview of all the structural information available in the for UniProt: P02671 (Fibrinogen alpha chain) at the PDBe-KB.

PDB

Overview of all the structural information available in the for UniProt: P02675 (Fibrinogen beta chain) at the PDBe-KB.

PDB

Overview of all the structural information available in the for UniProt: P02679 (Fibrinogen gamma chain) at the PDBe-KB.

PDB