Page 337 - Essential Haematology

Chapter 24 Platelets, blood coagulation and haemostasis / 323

ase after vascular injury, with plasma factor VIIa. Fibrinogen
TF is the sole initiator of thrombin generation and
Fibrinopeptide

fibrin formation. It is expressed on fibroblasts of the release Thrombin
adventitia and small muscle of the vessel wall and
in the blood stream on microparticles, and on other Fibrin monomer
non - vascular cells. One to two per cent of the total Hydrogen XIII
factor VII circulates in the activated form, but does bonding
not express proteolytic activity unless bound to TF. Fibrin polymer
The factor VIIa - tissue factor (extrinsic factor Xase)

complex activates both factor IX and factor X. Th e Transamidase XIIIa
bonding
factor Xa, in the absence of its cofactor, forms small
amounts of thrombin from prothrombin. Th is is Cross-linked

insufficient to initiate signifi cant fi brin polymeriza- fibrin

tion. Amplification is needed and this is discussed
next.
Figure 24.10 The formation and stabilization of fi brin.

Amplifi cation
The initiation pathway or extrinsic Xase is rapidly Fibrinogen has a MW of 340 000 and consists

inactivated by tissue factor pathway inhibitor of two identical subunits, each containing three
(TFPI) which forms a quaternary complex with dissimilar polypeptide chains ( α , β and γ ) which
VIIa, TF and Xa. Thrombin generation is now are linked by disulphide bonds. After cleavage

dependent on the traditional intrinsic pathway. by thrombin of small fibrinopeptides A and B from

Factor VIII and V are converted to VIIIa and Va by the α and β chains, fibrin monomer consists of
the small amounts of thrombin generated during three paired α , β and γ chains which rapidly
initiation. In this amplification phase the intrinsic polymerise.

Xase formed by IXa and VIIIa on phospholipid Some of the properties of the coagulation factors
2 +

surface in the presence of Ca activates suffi cient are listed in Table 24.2 . The activity of factors II,
Xa which then in combination with Va, PL and VII, IX and X is dependent upon vitamin K which
2 +
Ca forms the prothrombinase complex and results is responsible for carboxylation of a number of ter-
in the explosive generation of thrombin which acts minal glutamic acid residues on each of these mol-
on fibrinogen to form the fi brin clot. ecules (see Fig. 26.8 ).

Factor XI does not seem to have a role in Although factor VIII and V cofactors are not
the physiological initiation of coagulation. It has protease enzymes, they circulate in a precursor form
a supplementary role in the activation of factor that requires limited cleavage by thrombin for
IX (see above) and may be important at major expression of full cofactor activity.
sites of trauma or at operations and potentially
causes excess bleeding in factor XI defi cient
individuals. Endothelial c ells

Thrombin hydrolyses fibrinogen, releasing fi bri-

nopeptides A and B to form fibrin monomers (Fig. The endothelial cell has an active role in the main-

24.10 ). Fibrin monomers link spontaneously by tenance of vascular integrity. This cell provides

hydrogen bonds to form a loose insoluble fi brin the basement membrane that normally separates
polymer. Factor XIII is also activated by thrombin collagen, elastin and fibronectin of the subendothe-

together with calcium. Activated factor XIII stabi- lial connective tissue from the circulating blood

lizes the fibrin polymers with the formation of cova- (Fig. 24.8 ). Loss or damage to the endothelium
lent bond cross - links. results in both haemorrhage and activation of the