Biomedical Engineering Reference
In-Depth Information
Activating surface glycoprotein
Kallikrein
HMK
XIIa
XII
XIa
XI
VIIIa
IXa
IX
Xa
X
Figure 12.2 The steps unique to the intrinsic coagulation pathway. Factor XIIa can also convert prekal-
likrein to kallikrein by proteolysis, but this is omitted for the sake of clarity. Full details are given in the main
text. The fi nal steps of the coagulation cascade, which are shared by both extrinsic and intrinsic pathways,
are outlined in Figure 12.3
prekallikrein, yielding kallikrein (which, in turn, can directly activate more XII to XIIa).
factor XI, forming XIa.
Factor XIa, in turn, activates factor IX. Factor IXa then promotes the activation of factor X, but
only when it (i.e. IXa) is associated with factor VIIIa. Factor VIIIa is formed by the direct action
of thrombin on factor VIII. The thrombin will be present at this stage because of prior activation
of the intrinsic pathway.
12.2.2 Terminal steps of coagulation pathway
Both intrinsic and extrinsic pathways generate activated factor X. This protease, in turn, cataly-
ses the proteolytic conversion of prothrombin (factor II) into thrombin (IIa). Thrombin, in turn,
catalyses the proteolytic conversion of fi brinogen (I) into fi brin (Ia). Individual fi brin molecules
aggregate to form a soft clot. Factor XIIIa catalyses the formation of covalent crosslinks between
individual fi brin molecules, forming a hard clot (Figures 12.3 and 12.4).
Prothrombin (factor II) is a 582 amino acid, 72.5 kDa glycoprotein, which represents the cir-
culating zymogen of thrombin (IIa). It contains up to six
-carboxyglutamate residues towards
its N-terminal end, via which it binds several Ca 2 ions. Binding of Ca 2 facilitates prothrombin
binding to factor Xa at the site of vascular injury. The factor Xa complex then proteolytically
γ
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