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crystallographic structure of a human fibrin fragment with 2 ligands
Mass / length primary structure 3410 = 2 * (831 + 447 + 427) amino acids
Secondary to quaternary structure Heterohexamer 2α + 2β + 2γ
Isoforms α-1, α-2; γ-A, γ-B
Gene name (s) FGA , FGB , FGG
Drug information
ATC code B02 BB01 B02 BC10
Drug class Clotting factor

Cross-linking through thrombin

The fibrinogen is a glycoprotein , which in the liver of vertebrates formed and the blood plasma is distributed. During blood clotting, fibrinogen ( coagulation factor I ) is converted into fibrin by the serine protease thrombin (factor IIa) and calcium (factor IV) , which, as the “substrate for coagulation”, forms the thrombus together with cellular elements of the blood, namely the platelets .

Fibrinogen is composed of three subunits (α, β, γ). Mutations in the FGA - FGB - or FGG - gene can cause fibrinogen; Mutations in FGA can also cause familial type 8 amyloidosis .


Fibrinogen is a protein complex , a hexamer consisting of two α, β and γ subunits. The subunits are connected to one another via disulfide bridges in such a way that the amino terminus of all subunits forms the center of the complex, the so-called E domain, from which the individual monomers lead away as a coiled-coil structure. The carboxyl termini on the outside are called the D domain, so the simplified notation is: D-coil-E-coil-D (see figure).

Heteropolymers can be formed with fibronectin . About one third of the α subunits are phosphorylated .


Platelet aggregation

The activation of platelets leads to a conformational change of the receptor integrin α IIb β 3 , which is then able to bind fibrinogen with high affinity . Cross-linking of the platelets by fibrinogen is the result.

Fibrin synthesis

Fibrinogen is the starting substance for generating the thrombus. It is always dissolved in the blood. In the event of an injury, a cascade-like, multiple feedback process that takes place on the surface of the activated platelets is triggered to activate the procoagulant factors circulating in the plasma, at the end of which the formation of the central enzyme thrombin occurs . This cuts off the D domains of the fibrinogen hexamer (the small-molecule cleavage products are called fibrinopeptide A and  B ). The released fibrin monomers polymerize spontaneously to insoluble fibrin - clot . Only through further covalent cross-linking by means of factor XIIIa does the stable thrombus arise.

Lack of fibrinogen

The normal values ​​for fibrinogen in the human body are between 150 and 450 mg / dl, in pregnancy up to 600 mg / dl for physiological reasons. As an acute phase protein, it can quickly rise to over 1000 mg / dl in inflammatory processes. The fibrinogen determination is carried out in the context of the standard coagulation tests coagulometrically with the determination according to Clauss, derived from the Quick value or in whole blood by thromboelastometry .

Hereditary fibrinogen synthesis disorders

The congenital fibrinogen deficiency (afibrinogenemia or hypofibrinogenemia) is extremely rare (prevalence <1: 1,000,000) and often leads to severe hemorrhagic disorders at birth. The somewhat more frequent abnormal fibrinogen functions (dysfibrinogenemia), on the other hand, are usually clinically normal; Bleeding symptoms only appear here in exceptional cases.

Acquired fibrinogen deficiency

Dilution , loss or consumption are the main causes of an acquired fibrinogen deficiency in everyday clinical practice. In the course of reactive or therapeutic hyperfibrinolysis, the fibrinogen can drop below critical values ​​as a result of increased turnover. Acquired synthesis disorders occur with severe liver disease or asparaginase therapy . Pronounced fibrinogen deficiency can also occur perioperatively (e.g. in cardiac and neurosurgery ), in obstetric complications and in burns and shock conditions with massive blood loss, as can disseminated intravascular coagulation ( DIC ) in sepsis patients .

In the case of massive transfusions, it should be noted that fibrinogen is the first procoagulation factor to fall into the critical range (<100 mg / dl).

Therapy of fibrinogen deficiency

There is sufficient evidence that, in the case of bleeding, it is very important to correct a fibrinogen deficiency or a fibrinogen polymerization disorder as early as possible; this can be done by means of infusions of frozen fresh plasma (GFP), cryoprecipitate (fibrinogen-rich plasma fraction) or fibrinogen concentrates. The plasma concentration of fibrinogen should be increased to the reference range of at least 100 to 150 mg / dl. In the case of hyperfibrinolytic processes, these must first be stopped by using antifibrinolytics .

Individual evidence

  1. PDB  1FZC ; SJ Everse, G. Spraggon, L. Veerapandian, M. Riley, RF Doolittle: Crystal structure of fragment double-D from human fibrin with two different bound ligands . In: Biochemistry . tape 37 , no. June 24 , 1998, pp. 8637-8642 , doi : 10.1021 / bi9804129 , PMID 9628725 .
  2. a b c UniProt P02671 , UniProt P02675 , UniProt P02679
  3. Goldhaber, Colman, Clowes (Eds.): Hemostasis and Thrombosis: Basic Principles and Clinical Practice. Lippincott Williams & Wilkins, 2006, ISBN 0-7817-4996-4 , p. 826.
  4. ^ T. Lang, K. Johanning, H. Metzler, S. Piepenbrock, C. Solomon, N. Rahe-Meyer, KA Tanaka. The effects of fibrinogen levels on thromboelastometric variables in the presence of thrombocytopenia. In: Anesth Analg. 2009; 108, pp. 751-758, PMID 19224779 .
  5. SS Acharya, DM DiMichele. Rare inherited disorders of fibrinogen. In: Haemophilia. 2008; 14, pp. 1151-1158, PMID 16684009 .
  6. Cross-sectional guidelines for therapy with blood components and plasma derivatives. 4th edition. 2009.
  7. D. Fries, P. Innerhofer, W. Schobersberger: Time for changing coagulation management in trauma-related massive bleeding . In: Curr Opin Anaesthesiol . tape 22 , no. 2 , April 2009, p. 267-274 , doi : 10.1097 / ACO.0b013e32832678d9 , PMID 19390253 ( ).

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