Author: Ilaria D Amato
Date: 13/05/2009



Fibrinogen, known as Coagulation Factor I, is an esameric glycoprotein of 340 KDa composed of three pairs of non-identical polypeptide chains called Aα, Bβ and γ.
It’s synthesized by parenchimal hepatic cells and it’s found as a soluble protein in human plasma, in variable concentration of 160 to 400 mg/dl and as deposit in platelets’ alpha-granules. Genes FGA, FGB and FGG encoding for chain Aα, Bβ and γ, respectively, are located, in single copy and adjacent positions, in chromosome 4 (q31.3-q32.1), are ca. 6 (FGA), 8 (FGB) and 10.5 (FGG) Kb large and form a cluster of ca. 50Kb.


Your Favorite Gene SigmaFGA"FGB":"FGG":
Mw Kd705651

Genes FGA and FGG are oriented in the same direction and encoded in the opposite direction of FGB. Gene FGA has 6 exons and 5 intronic regions and at the sixth exon sustains an alternative splicing that encodes for 2 proteins: the first one is the chain Aα precursor of 644 amino acids, the second is an 866 amino acids polypeptide called isoform alpha-E (extended). Gene FGB has 8 exons and 7 intronic regions and encodes for a 491 amino acids polypeptide. Finally, FGG has 10 exons and 9 intronic regions and encodes for 2 isoforms by alternative splicing of exon 10, a predominant one of 437 amino acids and an alternative one of 453 amino acids.


Protein Amino acids Percentage


Early time course of the acute phase protein response in man. 1983

Acute Phase Proteins

CRP and fibrinogen mRNA synthesis is upregulated by IL-6 through STAT3 activation

All molecules involved in STAT3 signaling have the same Trp %

protein synthesis


post-translational modifications

The 3 primitive chains have a signal peptide of 19, 30 and 26 amino acids, respectively, that enables the translocation to rough endoplasmic reticulum where a signal peptidase removes it allowing the forming of 625, 461 and 411 amino acid mature chains.
The six chains assembly to form the esameric protein via an elaborate process that provides the initial dimeric association of Aα-γ and Bβ-γ polypeptides; subsequently there is the association of the trimeric intermediate protein Aα-Bβ-γ and finally the forming of the esameric protein (Aα-Bβ-γ) 2 . The forming of 12 intrachain disulfuric bridges and 17 interchain disulfuric bridges stabilizes the tertiary structure.
After the assembling, fibrinogen has a linear array of 3 nodules held together by a very thin thread, the central node is called E-domain, and consists of the association of the six N-terminal domains; E-domain is joined with the 2 lateral nodules called D-domain (the C-terminal domain of the Bβ and γ chains) by two coiled-coil regions that are the 3 chains Aα, Bβ and γ, that have a secondary α-helix structure, wrapped on themselves.


Fibrinogen, called Coagulation Factor I, is a proenzimatic protein excreted by parenchimal hepatic cells. In circle, it’s converted into fibrin by thrombin to synthesize the soluble clot, that will be transformed into definitive clot by the XIII coagulation factor with the presence of Ca ++ ions.
Moreover, fibrinogen is also a cofactor of the platelet’s aggregation, in fact during the coagulation process it’s used by activated platelets as molecular bridge to form platelet’s aggregates.


Fibrinogen Disorders


Quantitative Fibrinogen Disorders

The quantitative fibrinogen disorders belong to CID, Coagulation Inherited Disease, with a prevalence of 1-2:1.000.000 and depend on the presence of mutations that affect the fibrinogen genes. Afibrinogenaemia is a recessive autosomal disorder due to the presence of homozygous mutations o 2 mutations that affect the 3 genes in the same chromosome (phenomenon called “complex heterozygosis”). The patients affected have functional protein levels not registrable, extremely low or not registrable immunoreactive protein levels and can incur hemorrhagic episodes with variable severity.
Hypofibrinogenaemia is the state of heterozygosis of Afibrinogenaemia, and it is therefore a dominant autosomal disorder. The patients affected have a functional and immunoreactive protein level of fibrinogen under the minimum normal level, that is 160 mg/dl. Normally they are asymptomatic, but can incur hemorrhagic episodes.

Qualitative Fibrinogen Disorders

These disorders are defined by the presence of an abnormal variant of plasmatic fibrinogen (Dysfibrinogenaemia), usually associated with normal antigenic levels of protein, but in some cases they could present a reduction of the circulating protein (Hypo/Dysfibrinogenaemia).
The hereditary dysfibrinogenaemia is generally associated with an hereditary dominant autosomal pattern, with many heterozygous patients for the mutation causing the disease.


High levels of fibrinogen could be due to hepatic hepatitis, atherosclerosis, rheumatoid arthritis, hepatic cirrhosis, viral hepatitis, gout, pregnancy, myocardial infarction, renal failure, multiple myeloma, oral contraceptive, traumas and burns.
Lower levels of fibrinogen could be due to prostate cancer, hemorrhagic events, phosphoric intoxication, acute infections, liver failure and use of anticoagulants.

2017-08-03T14:51:08 - Gianpiero Pescarmona

Uncoordinated expression of fibrinogen compared with thrombospondin and von Willebrand factor in maturing human megakaryocytes. 1989

  • The localization of three known alpha-granule proteins, thrombospondin (TSP), von Willebrand factor (vWF), and fibrinogen (Fg) has been studied in human megakaryocytes (MK) by immunofluorescence and immunoelectron microscopy. For this study, highly purified populations of MK were prepared from human bone marrow either by counterflow centrifugal elutriation or by cell culture from normal subjects and from two patients with megakaryoblastic leukemia. In normal bone marrow immature MK, TSP, and vWF were observed in the Golgi-associated vesicles and in small immature alpha-granules; in mature MK, they were found in the matrix of the mature large alpha-granules. Surprisingly, Fg was detected neither in the Golgi area, nor in the small precursors of alpha-granules; it was only found in the mature alpha-granules but this labeling was generally weaker than in blood platelets. In order to confirm these differences between the expression of Fg and vWF or TSP additional studies were performed on cultured maturing MK: immunofluorescent and ultrastructural immunogold labeling confirmed that vWF appeared early in the maturation while the same immature MK were negative for Fg. In the late maturation stage, the three proteins were detected in the alpha-granules. In order to know whether Fg was lately synthesized or endocytosed from the outside medium, normal MK were grown in the presence of either normal or afibrinogenemic plasma, and normal serum. Fg was detected only in the alpha-granules of MK grown in normal plasma. Similar results were observed with malignant MK, whose maturation was independent of the culture conditions. In conclusion, this study brings immunocytochemical evidence that vWF and TSP are synthesized by immature MK, whereas Fg appears later in the MK alpha-granules and its expression is dependent of the presence of an exogenous Fg source.
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