Biomedical Engineering Reference
In-Depth Information
We hope that this long list has not been too tedious. We believe it can be
very useful not only for understanding the rest of the paper, but also as a kind of
glossary to move around in the field of blood coagulation. Having introduced all the
characters, let us now see how they play the game.
7.4
The Cell-Based Model for Secondary Hemostasis
During the last decade it became apparent that the
Cascade
(or
Wa t e r f a l l
) model
for secondary hemostasis elaborated during the 1960s and long considered the
correct explanation of the complex blood coagulation process was in need of a
deep revision. In Sect.
7.6
we will illustrate both the model and the reasons for its
final rejection. The model that took its place is known as the
Cell-Based Model
and has its roots in many papers (see [
56
,
67
,
106
,
160
,
161
,
206
,
216
,
219
]and
the literature quoted therein). The very synthetic exposition in [
22
] is interesting
because it contains some details not frequently recalled elsewhere.
According to the cell-based model, the fibrin production process goes through
four steps (
initiation, amplification, propagation, termination
). Fibrinolysis goes in
parallel and becomes visible over a longer time scale. The necessity of having two
separate time scales comes from the fact that the clot has to be formed soon, but
it has to dissolve slowly. Indeed it has to stay in position long enough to allow
wound healing (at least partial) and it must not break into pieces which would be
dangerously released in the bloodstream.
7.4.1
Secondary Hemostasis
1.
Initiation
(Fig.
7.3
)
Once the tissue factor has become exposed to blood at the injury site, the complex
FVII-TF is readily formed, and the tiny amount of FVIIa which normally circulates
in blood gives rise to the FVIIa-TF complex.
45
The latter activates FVII-TF and (
at a low rate
) FIX, FX. Now we have a small
amount of FIXa, FXa (in turn able to activate more of the complex FVII-TF). In
particular, at this stage, a small quantity of FVa is produced as the result of the action
of FXa on FV. The ability of FXa to activate FV has been proved long ago (in [
176
],
see also [
82
]). Though the main activator of FV is thrombin and the activation rate by
FXa is orders of magnitude less, the production of FVa even in very small quantity
45
Some FVIIa can reach TF in nonvascular tissues even in the absence of a lesion [
279
], thus
making FIXa and FXa accidentally available. However, coagulation does not start because it
requires, for instance, the intervention of platelets, which are not available out of the bloodstream.
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