Biomedical Engineering Reference
In-Depth Information
thrombus
). Platelets-vWF adhesion is by no means a simple phenomenon. It is me-
diated by mechanical stress and occurs in two steps. We have mentioned the two
platelets membrane receptors GPIb and GPIIb-IIIa, which both have a complex in-
ternal structure that will not be described here. In the high stress conditions present
at the vessel wall
11
the receptors of the first class have a large adhesion rate to vWF
(at some specific site: we omit such details), but they also have a large dissociation
rate. This results in a relatively slow motion of platelets over the wound site. The
receptors of the second class have a much lower combination rate, but their binding
to vWF is irreversible. The persistence time of platelets over the wound site is di-
lated by the GPIb-vWF interaction and this permits an efficient intervention of the
GPIIb-IIIa receptors. It must be remarked that the role of shear stress is of crucial
importance in activating the interaction between platelets and vWF. This is true also
in a later phase in which the same kind of bonds are established and have a key role
in the formation of the clot. Platelets cross binds are also provided by fibrinogen.
The above description is extremely concise. A basic reference is [40], which fo-
cuses on the role of receptors not only in the binding action, but also on the regulation
of the platelets cytoskeleton and on their mechanical behaviour. A particularly inter-
esting aspect is platelets “rolling” along the blood vessel wall. While the rolling of
WBCs (which possess a spheroidal shape) was described already in 1839 [94], only
much later [46] the mechanism of leukocyte tethering to walls was explained. That
platelets also exhibit rolling followed by tethering “when required” was only estab-
lished in 1995, [27]. Platelets are naturally more concentrated in the periphery of
blood vessels in a regime of laminar flow [91], however their discoidal shape is not
best suited for rolling. Indeed, as soon as platelets become exposed to fixed vWF
they experience a rapid morphological conversion, assuming the shape of “spiny
spheres”, which greatly favors rolling. This and the subsequent morphological mod-
ifications require cytoskeleton remodelling in which both the receptors-vWF inter-
action and the shear stress play a role. As a matter of fact, it has been observed that
such modifications occur very slowly under low stress conditions.
3.2.3 The cell-based model for the blood clot formation (secondary
hemostasis)
A blood coagulation model that was widely accepted for almost forty years is the
one that became known as the
Cascade model
, because it recognized for the first
time that clotting was the result of cascades of chemical reactions. Its origin can be
traced in two papers appeared independently in 1964 ([18, 48]). The model was char-
acterized by an
intrinsic pathway
(originated in the blood stream) and an
extrinsic
pathway
(initiated at the wound site), both merging into a
common pathway
.Itwas
11
Roughly speaking, a strain rate of 1000 s
−
1
is considered to fully activate the adhesion process.
m there can be strain rates in the range 500-5000 s
−
1
[88].
Stenosis (lumen reduction) due to atherosclerotic plaques can raise strain rate beyond 10000 s
−
1
.
Of course translating strain rate into shear stress requires a rheological model for blood. This is a
delicate and controversial matter to which we will return later on. Here we just point out that, in
view of the relevance of stress, the size of the vessel generally plays an important role.
In arterioles in the range of 10-50
μ
