Biomedical Engineering Reference
In-Depth Information
Fig. 7.5
Sketch of the
thrombin concentration vs.
time
400
300
200
100
0
300
600
900
Time (sec)
thrombin production rate shown in the sketch in Fig
7.5
(for experimental evidence
of this behavior, see, e.g., [
40
,
161
,
186
]).
Besides continuing actions (Thr. 1-3), thrombin performs two more important
tasks:
•
(Thr. 4) transition from FI (
fibrinogen
) to polymer FIa (
fibrin
),
•
(Thr. 5) activation of FXIII.
Fibrinogen polymerization occurs at a high rate. From now on the fibrin
network traps blood constituents and we may say that the clot progression is
fibrin
dominated
. Fibrin generation is just the first step of the network production, which
results from the aggregation of polymer chains into fibers [
79
]. The role of FXIIIa is
to
consolidate
the fibrin network by forming cross links among fibers. Clots lacking
cross links
are unstable, as proved by the fact that a nontrivial bleeding disorder is
associated with deficiency of FXIII.
A further remark is about the fact that, while FVa is effectively inactivated by
APC (Activated Protein C) when not included in the prothrombinase complex, it
appears to be protected from this action if combined with FXa. Protection of FVa
fromAPCexertedbyFXawasestablishedin[
181
,
243
].
4.
Termination
(Fig.
7.7
)
As we have said several times, the biological processes of clot formation and dis-
solution are the result of an unbalance between contrasting elements which happen
to be first in one direction and then in the opposite. If starting and accelerating the
growth of a thrombus is important for arresting bleeding, terminating it is absolutely
essential to prevent vessel occlusion. We have seen how thrombin helps in confining
clotting. By means of the very same reaction it actually starts the termination
mechanism:
•
(Thr. 6) The thrombin-TM complex activates PC.
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