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 (HMW) and
low-molecular weight (LMW) fibrinogen.
They act differently in terms of fibrin
network characteristics and wound
healing. HMW fibrinogen produces
a fibrin clot with thick fibres and limited
fibre density, whereas the LMW
fibrinogen produces clots with thin fibres
at higher density. 5 The low-density clots
produced by HMW fibrinogen promote
angiogenesis in wound healing at a better
rate than high-density clots.
A second very important role of
Figure 1 The role of fibrinogen as a pro-coagulant factor within the cell-based
coagulation process
FXIIIa
Fibrinopeptides
Fibrinogen
Fibrin polymer Plasmin
Platelet FDP
Fibrin monomer
GPIIb/IIIa
Thrombin
Platelet
PAR
Thrombin
TF
Endothelial lesion
6
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