Biomedical Engineering Reference
In-Depth Information
Fig. 3.5.
Cell-based model:
Termination phase
of blood coagulation
3.2.4 Fibrinolysis
Clots respond to an immediate need and persist for the time needed to healing the
wound, i.e. repairing the injured tissues, which is another complicated process that
will not be dealt with here. However they cause an alteration of the natural blood flow
and they have to be removed. Their elimination must be gradual, without delivering
in the blood stream fragments that may cause embolism. Thus demolishing a blood
clot is a delicate and important operation that has its own chemical machinery. A clot
must incorporate some fibrinolytic element already during the growth process. Very
much like coagulation, fibrinolysis proceeds through activation of (not numbered)
factors, which have in turn their own inhibitors. Here is a list of the intervening
substances:
•
Plasminogen
(secreted by the liver);
•
Plasmin
(activated plasminogen): it is responsible for the dissolution of Fibrin;
•
tissue Plasminogen Activator (tPA)
;
•
urokinase(uPA)
;
•
Plasmin Activator Inhibitor 1 and 2 (PAI-1, PAI-2)
;
•
antiplasmins
(plasmin inhibitors):
α
2antiplasmin
and
α
2macroglobulin
;
•
Thrombin Activatable Fibrinolysis Inhibitor (TAFI)
.
Plasminogen is converted to plasmin by tPA and urokinase. It binds to Fibrin during
the clotting process, so its activation can immediately prompt fibrinolysis in situ.
However, activators are slowly emitted at the injury site, so that plasmin is produced
in a progressive way and the clot regression takes place at a low speed. Embedding
of plasminogen in the clot body is necessary to prevent the action of inhibitors at
a too early stage. Plasmin itself is able to stimulate the production of more tPa and
urokinase, so here too we have a positive feedback. The action of TAFI is to protect
Fibrin. During the first stage of fibrinolysis the Fibrin fragments may recombine,
slowing down the process (an intriguing aspect from the point of view of mathema-
tical modelling) (Fig. 3.6).
Remark 2.
We have mentioned that the clotting process is linked to the fluid dynami-
cal problem via the shear stress exerted by blood. In [85] it has been suggested that
one more coupling of the chemistry with the flow can be created by convection,
