Biomedical Engineering Reference
In-Depth Information
17.5.3 P
LATELET
A
DHESION
AND
A
CTIVATION
Platelets are responsible for the formation of the initial plug in damaged vessels, subsequently cata-
lyzing thrombus formation at that site.
5,17
Platelets normally fl ow along with the blood, until at a site
of vessel damage the underlying extracellular matrix is exposed. Collagen and von Willebrand fac-
tor (vWF) are exposed and the platelets contain receptors for these proteins on their surface. Revers-
ible binding of vWF to the platelet membrane glycoprotein GP1b-V-IX or integrin-αIIbβ3 will slow
down the platelets, causing them to roll over the damaged vessel wall. Now the platelets can bind to
collagen via the collagen receptors GP-VI and integrin α2β1. GP-VI is the main receptor on platelets
for collagen binding. Additionally, binding of collagen to integrin α2β1 has been demonstrated to
result in activation of the platelets. The surface of activated platelets becomes enriched with nega-
tive charge by the active translocation of phosphatidyl serine from the inner leafl et of the membrane
to the outer leafl et, resulting in an increased negative charge on the outer surface.
5,48
This negatively
charged surface is an excellent substratum for the propagation of the coagulation response. The for-
mation and activity of the protein complexes that form FXa and thrombin are highly dependent on
this negatively charged lipid surface for effi cient activity. Furthermore, upon activation of platelets,
these will excrete several chemical signals (adenosine diphosphate (ADP), thromboxane A2) that
will induce further platelet adhesion (platelet aggregation) and activation. Activated integrin αIIbβ3
can bind to fi brinogen and act as a link between platelets, resulting in aggregation.
17,49
Apart from binding to the subendothelial layers upon vessel damage, platelets also bind to
synthetic surfaces. The binding and subsequent activation of platelets is accompanied by a marked
change in morphology that can be easily monitored by electron microscopy (Figure 17.8).
50
The
platelets have a round morphology directly after binding the surface. Then they form spike like
extrusion from the main cell body, resulting in a dendritic cell shape. The platelets will start
FS
R
D
S
FS
FIGURE 17.8
Adhered and activated platelets on a polyurethane sheet. Different stages of platelet activation
can be observed. Round, freshly adhered (R), dendritic (D), spreading (S), and fully spread (FS). The scale
bar represents 10 μm.
