HPE CSL Managing Perioperative Bleeding handbook - Page 6

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 hospitalpharmacyeurope.com