pathophysiology
Pathophysiology
of fibrinogen
Fibrinogen is involved in both primary and secondary haemostasis, playing an
important role in platelet aggregation and the establishment of a fibrin network, and
fibrinogen concentrate plays a key role in a range of acute and emergency situations
Marco Ranucci MD FESC
Director of CardioThoracic
and Vascular Anaesthesia
and ICU IRCCS Policlinico
San Donato, Milan, Italy
Fibrinogen (coagulation factor I) is the major
plasma protein coagulation factor. It is
synthesised in liver hepatocytes and its plasma
concentration range is 2.0–4.5g/l. 1
The fibrinogen molecule is a 340 kDa
glycoprotein composed of two sets, each
comprising three peptide chains: Aα, Bβ and γ,
linked by disulphide bridges. 1,2
The role of fibrinogen in the
coagulation system
There are two major mechanisms by which
fibrinogen contributes to the haemostatic process
(Figure 1). The first is triggered by thrombin
(coagulation factor IIa), which cleaves the
fibrinopeptides A and B from the Aα and Bβ
chains. Through this cleavage, fibrinogen is
converted into fibrin monomers. 3 Subsequently,
and through the action of coagulation factor
XIIIa (coagulation factor XIII activated by
thrombin), the fibrin network is stabilised
(fibrin polymerisation) by a cross-linking process
based on transglutaminase reactions between
two γ chains or one γ- and one α-chain. 4
The fibrin network is subsequently lysed by the
fibrinolytic system (through the conversion of
plasminogen into plasmin) with the release of
fibrin degradation products (FDP). Markers of
fibrin formation are the fibrinopeptides
A and B, and of its breakdown, the FDP.
Plasma fibrinogen is present in different
forms, mainly related to the degradation of the
C-terminal region of the α-chains. The two
principal forms are high-molecular weight
Figure 1
The role of fibrinogen as a pro-coagulant factor within the cell-based
coagulation process
FXIIIa
Fibrinopeptides
Fibrinogen
Fibrin polymer
Plasmin
Fibrin monomer
GPIIb/IIIa
Thrombin
Platelet
Platelet
PAR
Thrombin
TF
Endothelial lesion
6
HHE 2018 | hospitalhealthcare.com
FDP