Biomedical Engineering Reference
In-Depth Information
the clotting process has been determined experimentally by suppressing it in mice
and observing the correspondingly induced bleeding disorder.
Among the many factors that will be mentioned later, we want to point out imme-
diately the importance of FII (
Prothrombin
), FIIa (
Thrombin
), FI (
Fibrinogen
), FIa
(
Fibrin
). Thrombin performs various different actions of fundamental importance
that will be discussed in detail. In particular, in the most active stage of the process,
it acts on Fibrinogen, changing it to a form which polymerizes rapidly, eventually
giving rise to the Fibrin network which makes the skeleton of the gel trapping the
various blood component (i.e. the clot).
von Willebrand Factor (vWF)
This factor deserves a special attention because of its multiple roles. It bears the
name of the Finnish physician Erik von Willebrand, who first described (1926) a
bleeding disorder (today called von Willebrand disease), distinguishing it from the
ones known at that time. The disease was later associated with the deficiency of
the factor now bearing his name. vWF is a massive multimer (a chain of identical
elements, not as numerous as in a polymer, it can be an oligomer) which is present in
different lengths and is sensitive to shear stress, in the sense that stretched molecules
are more active. The largest variety resides in the endothelium of blood vessels wall.
vWF also circulates in the blood (one of the largest circulating proteins), associated
in a
complex
(see below) with FVIII (the vWF bound in the complex is not active).
It intervenes in the so called
primary hemostasis
(Sect. 3.2.2) and during the main
phase of clotting, because it binds with platelets in the presence of a sufficiently high
stress (hence it brings a coupling of the biochemistry with the mechanics).
The vast majority of vWF is secreted in the endothelial cells, and a small per-
centage is stored in cytoplasmic granules (Weibel-Palade bodies) of many cells. We
have seen that it is also contained in the granules of platelets and that it is secreted
after their activation. The circulating FVIII-vWF complex is dissociated during the
fastest phase of the coagulation process, thus providing an intense source of both
factors in a free state.
A very detailed analysis of the structure and of the functions of vWF can be found
in the excellent paper [78]. Another more concise and equally recommendable read-
ing is [76].
Tissue Factor (TF)
Also known as
Thromboplastin
(or FIII), TF is expressed by cells which are normally
not in contact with blood. It is known (see e.g. [19])
7
that it is also produced by some
WBCs (more precisely by
monocytes
) for instance as a consequence of inflamma-
tory processes. Today there is a general consensus on the fact that clot formation is
initiated by the exposure of TF to blood at the injury site. See also the section on
Deep Vein Thrombosis (Sect. 3.3.3).
7
TF production by monocytes is not a recent discovery. See e.g. [34].
