Biomedical Engineering Reference
In-Depth Information
Fig. 3.2.
Cell-based model:
Amplification phase
of blood coagulation
Amplification
This is a transition stage towards the final burst of Thrombin (Fig. 3.2). FIXa pro-
duced in the previous step can dissociate and diffuse to platelets that keep accumu-
lating at the wound site. It is not affected by TFPI and (differently from FXa) only
very slowly by AT-III, so it becomes available to platelets. The small amount of
Thrombin produced in the previous stage activates FV to FVa on platelets surfaces
and breaks the complex FVIII-vWF, at the same time activating FVIII to FVIIIa. The
free vWF acts as a cross link for activated platelets in the presence of stress. A sim-
ilar action is performed by fibrinogen. One more activation performed by Thrombin
is the one of FXI
12
to FXIa, stimulating further production of FIXa. These events
trigger the main phase of coagulation. Platelets are now activated.
Propagation
The now available FVIIIa and FIXa readily produce the
Tenase
complex FVIIIa-
FIXa, whose main task is to provide FXa on the platelets surface. We recall that
FXa (having the key role of producing the
Prothrombinase
complex together with
FVa), present in the early stage of the process, cannot diffuse and therefore it has
to be produced effectively within the growing thrombus. Factor Va, produced by
Thrombin in the amplification stage, binds to FXa (as it did in the initiation stage),
so that Prothrombinase produces more Thrombin, which in turn creates more FVa.
Thus all the key ingredients enter a highly positive feedback process (about 95 % of
Thrombin is produced during this stage [51]), see Fig. 3.3.
The abundance of Thrombin makes the final step of the Fibrin network formation
practically immediate. Platelets keep binding among themselves thanks to the vWF
liberated (as long as sufficient shear stress is present at the periphery of the clot) and
they bind to Fibrin too (the resulting forces acting on Fibrin lead to a mechanical
contraction of the clot). The Fibrin network progressively entraps all blood con-
stituents. A further consolidation of the clot is induced by FXIIIa, also produced by
12
A large debate is going on the origin and the functions of FXI [56, 83].
