Fibrinogen

Fibrinogen is a glycoprotein that is synthesized in the liver of vertebrates and into the blood plasma. Fibrinogen ( clotting factor I) in blood clotting by the serine protease thrombin ( factor IIa), and calcium ( Factor IV ) is converted to fibrin, which forms the "substrate to the clotting " along with cellular elements of blood, namely platelets, the thrombus.

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

  • 3.1 Hereditary Fibrinogensynthesestörungen
  • 3.2 Acquired Fibrinogenmangelzustände
  • 3.3 Treatment of Fibrinogenmangels

Structure

Fibrinogen is a protein complex, one composed of two α -, β - and γ - subunits hexamer. The subunits are linked via disulfide bridges to each other such that the amino terminus of all the subunits forming the center of the complex, the so-called E- domain of the lead away the individual monomers as a coiled-coil structure. The carboxyl termini on the outside are called D- domain, so that the simplified notation is D -coil -E -coil -D ( see figure).

It can heteropolymers are formed with fibronectin. About one- third of the α - subunits are phosphorylated.

Function

Platelet aggregation

The activation of platelets leads to a conformational change of the receptor integrin aIIbb3 who is able to bind fibrinogen then with high affinity. A cross-linking of platelets by fibrinogen is the result.

Fibrin synthesis

Fibrinogen is the starting material for the production of the thrombus. It is constantly present dissolved in the blood. With an injury, a cascade-like, multiple -feedback and expiring on the surface of activated platelets, the process of activation of circulating plasma procoagulant factors is triggered at the end of the formation of the central enzyme thrombin is. This cuts the D- domains of the hexamer from ( the small-molecule cleavage products are called fibrinopeptide A and B). The released fibrin monomers spontaneously polymerize to insoluble fibrin clot. Only by further covalent cross-linking by factor XIIIa gives the stable thrombus.

Fibrinogen

The standard values ​​for fibrinogen are in the human body between 150 and 450 mg / dl in pregnancy physiologically limited to 600 mg / dl. As an acute phase protein in inflammatory processes, it can quickly rise to over 1000 mg / dl. The fibrinogen coagulometrically done within the framework of standard clotting tests with the determination according to Clauss, derived from the prothrombin time or in whole blood by thromboelastometry.

Hereditary Fibrinogensynthesestörungen

Extremely rare (prevalence < 1:1,000,000 ) is the congenital fibrinogen deficiency ( afibrinogenemia or Hypofibrinogenamie ), often leading at birth in severe hemorrhagic disorders. The somewhat more frequent abnormal Fibrinogenfunktionen ( Dysfibrinogenämien ), however, are usually clinically silent; Bleeding symptoms occur here only in exceptional cases.

Acquired Fibrinogenmangelzustände

Dilution, loss or consumption are the main causes of acquired fibrinogen deficiency in clinical practice. As part of a reactive or therapeutic fibrinolysis fibrinogen may drop below critical levels due to increased sales. Acquired synthesis disturbances occur in severe liver disease or a asparaginase. Also perioperatively (eg in cardiac surgery and neurosurgery ), obstetric complications and burns and shock states with massive blood loss may lead to pronounced Fibrinogenmangelzuständen, as well as disseminated intravascular coagulation ( DIC) in sepsis patients.

With massive transfusions should be noted that fibrinogen was the first Prokoagulationsfaktor in the critical region decreases (<100 mg / dl).

Therapy of Fibrinogenmangels

There is ample evidence that bleeding at the earliest possible correction of a Fibrinogenmangels or a fibrinogen Polymerisationsstörung is very important; this can be done by means of infusions of fresh frozen plasma ( CFP), cryoprecipitate ( fibrinogen-rich plasma fraction ) or fibrinogen concentrates. The plasma concentration of fibrinogen should in this case be raised to the reference area of at least 100 to 150 mg / dl. In hyperfibrinolytic processes they must first be stopped by application of antifibrinolytic drugs.

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