Biomedical Engineering Reference
In-Depth Information
in coagulation, including both the extrinsic and intrinsic pathways, and the poten-
tial to utilize the broad base of experimental data to refine modeling approaches
and extend them to clinically novel areas such as DIC presents both an opportunity
and a challenge.
The basic procedure described in our previous studies with the trypsin system
was used for modeling blood coagulation [9]. The system to be modeled needs to
first be described in terms of interactions and stoichiometry, and then experimental
kinetic observations are required to refine the initial model to a final working
model. The first step in applying this procedure required the delineation of the pro-
cess from vascular injury through clot formation. Extrinsic blood coagulation is ini-
tiated by vascular injury, which exposes tissue factor to the bloodstream. This
exposure results in activation of the extrinsic pathway, which is shown as the bold
set of reactions in Figure 11.11. Once thrombin is produced by the initial cascade of
zymogen activation reactions, it then participates in many feedback reactions,
including activation of the intrinsic pathway, which can supplement the extrinsic
pathway (Figure 11.12). The extrinsic and intrinsic pathways cooperate to produce
cross-linked fibrin (i.e., the blood clot) from fibrin, thus effecting repair of the
injury.
The initial SAN representation of the coagulation system is presented in Figure
11.13 [10]. The figure shows five pathway segments that combine to yield the repre-
sentation of the entire system. The segments include (1) initiation, (2) Factor
VIII-Factor IX complex formation, (3) Factor V-Factor X complex formation, (4)
Contact activation (intrinsic) pathway
Damaged surface
Tissue factor
(extrinsic) pathway
Trauma
TFPI
XIIa
XII
VII
VIIa
IXa
XI
VIII
Tissue factor
Trauma
IX
XIa
VIIIa
Antithrombin
X
X
Xa
Va
Thrombin
(IIa)
Prothrombin
(II)
Common
pathway
V
Fibrinogen (I)
Fibrin (Ia)
Active protein C
XIIIa
XIII
Protein S
Cross-linked
fibrin clot
Protein C +
thrombomodulin
Figure 11.11
Blood coagulation cascade, showing intrinsic and extrinsic pathways. (Courtesy of
Wikipedia.)
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