432
Chapter 12
along intact endothelium in both directions? One important
reason involves the ability of the adjacent undamaged endo-
thelial cells to synthesize and release the eicosanoid known as
prostacyclin
(also termed prostaglandin I
2
,
PGI
2
), which is
a profound inhibitor of platelet aggregation. Thus, whereas
platelets possess the enzymes that produce thromboxane A
2
from arachidonic acid, normal endothelial cells contain a dif-
ferent enzyme that converts intermediates formed from ara-
chidonic acid not to thromboxane A
2
, but to prostacyclin
(
Figure 12–73
). In addition to prostacyclin, the adjacent
endothelial cells also release
nitric oxide,
which is not only a
vasodilator (Section C) but also an inhibitor of platelet adhe-
sion, activation, and aggregation.
To reiterate, the platelet plug is built up very rapidly and
is the primary mechanism used to seal breaks in vessel walls.
In the following section, we will see that platelets are also
essential for the next, more slowly occurring hemostatic event:
blood coagulation.
Blood Coagulation: Clot Formation
Blood coagulation,
or
clotting,
is the transformation of
blood into a solid gel called a
clot
or
thrombus
and consist-
ing mainly of a protein polymer known as
brin.
Clotting
occurs locally around the original platelet plug and is the
dominant hemostatic defense. Its function is to support and
reinforce the platelet plug and to solidify blood that remains
in the wound channel.
Figure 12–74
summarizes, in very simplifi ed form, the
events leading to clotting. These events, like platelet aggregation,
are initiated when injury to a vessel disrupts the endothelium
PGI
2
PGI
2
NO
PGI
2
NO
PGI
2
Collagen
Blood vessel
Platelet plug
TXA
2
Figure 12–73
Prostacyclin (PGI
2
) and nitric oxide (NO), both produced by endothelial cells, inhibit platelet aggregation and therefore prevent the spread of
platelet aggregation from a damaged site. TXA
2
= thromboxane A
2
.
Stabilized fibrin
Loose fibrin
XIIIa
XIII
Thrombin
Fibrinogen
Prothrombin
Enzyme
Inactive plasma protein
Enzyme
Inactive plasma protein
Cascade of plasma
enzyme activations
(requires activated
platelets, plasma
cofactors, and Ca
2+
)
+
Vessel damage
Exposure of blood
to subendothelial tissue
Figure 12–74
Simplifi ed diagram of the clotting pathway. The pathway
leading to thrombin is denoted by two enzyme activations,
but the story is actually much more complex (as Figure
12–76 will show). Note that thrombin has three different
effects—generation of fi
brin, activation of factor XIII, and
positive feedback on the cascade leading to itself.
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