Page 191 - Basic Monitoring in Canine and Feline Emergency Patients

VetBooks.ir PAI-1 Plasminogen PAI-1

XII II, venous
plasmin uPA tPA occlusion

Plasmin
Fibrin
D-
Dimers
TAFI
Fibrin

FDPs
Fibrin

Fig. 9.6. Fibrinolysis with endogenous inhibitors. The same fibrinolysis process as shown in Fig. 9.5 is shown here.
The three major fibrinolysis inhibitors found within the body have been added to the figure to show their sites of
activity. Thrombin activatable fibrinolysis inhibitor (TAFI) is produced in response to thrombin (II) and blocks the ability
of plasmin to recognize a clot by removing signature lysine residues from the surface of the clot. Plasmin activator
inhibitor (PAI-1) will inhibit tissue plasminogen activator (tPA) and urokinase plasminogen activator (uPA) so that
less plasmin is formed. Finally, α-2 antiplasmin (α2AP) directly binds to plasmin to inhibit its activity. FDPs, fibrin
degradation products.

Taken together, fibrinolysis and fibrinolysis inhibi- where coagulation is occurring). When thrombin
tors exquisitely balance the need for a clot with and thrombomodulin bind together, proteins C/S
making the clot too large. are activated and they in turn inactivate factors
V and VIII so that the intrinsic factor tenase com-
plex and the prothrombinase complexes cannot
Anticoagulation
be formed.
The body also has a host of endogenous anticoagu- Heparan sulfate (the endogenous form of hepa-
lants which work to control the formation of the rin) is also bound to the endothelial cell wall and
clot itself (rather than simply breaking down the will work in concert with circulating antithrombin
clot once it forms via fibrinolysis; Fig. 9.7). Tissue to inactivate factor X and thrombin. Other endog-
factor pathway inhibitor will inhibit the initiation enous anticoagulants work to directly inhibit factor
phase of secondary hemostasis by blocking the X (α-1 protease inhibitor) and thrombin (α-2 mac-
activation of Factor X, specifically by inhibiting the roglobulin). Any inhibition of factor X and/or
extrinsic factor tenase complex. Tissue factor path- thrombin will inactivate the prothrombinase com-
way inhibitor is stored in platelets and endothelial plex and/or cleavage of fibrinogen to fibrin.
cells so as to be close to the site of action and is Coagulation is a complex interplay of processes.
released in response to heparin or is bound to lipo- It is important to remember that: (i) all processes
proteins and circulates through the body. (coagulation, fibrinolysis, anticoagulation, and anti-
Additionally, protein C and protein S are endog- fibrinolysis) are occurring simultaneously; (ii) every-
enous anticoagulants affecting mainly the amplifi- thing occurs on a phospholipid bilayer rather than in
cation and propagation phases. When thrombin space; and (iii) thrombin is the only molecule that is
is formed, some of it binds to thrombomodulin procoagulant, anticoagulant, pro-fibrinolytic, and
(which is found on the same endothelial cell surface anti-fibrinolytic all at the same time.

Coagulation 183