Page 187 - Basic Monitoring in Canine and Feline Emergency Patients

Aggregation
VetBooks.ir Initiation Activation Platelet vWF GpIIb/IIIa vWF Platelet GPIIb/IIIa

Platelet Platelet Platelet
Platelet

GPIIb/IIIa GPVI GPIb/V/IX GpIIb/IIIa GpVI GPIb/V/IX GpIIb/IIIa GpVI

Collagen Collagen Collagen GPIb/V/IX
TF vWF TF vWF TF vWF

Damaged endothelial surface
Fig. 9.2. The stages of platelet plug formation. Initiation occurs when exposed collagen/subendothelial factors and
von Willebrand’s factor (vWF) on the endothelial surface interacts with platelet surface glycoprotein receptors GPIIb/
IIIa, GPIb/V/IX, and GPVI on the cell surface. Activation then involves a change in platelet shape from discoid to round
with pseudopods. Additionally, the activity of various enzymes and mediators released from the platelet granules (see
the text for more information) leads to a change in the signaling milieu on the platelet’s surface. Finally, aggregation
describes the connection of various activated platelets with each other to form a platelet plug. Typically, aggregation is
facilitated by GPIIb/IIIa expressed on the surface of each activated platelet with vWF released from the alpha granules
of the activated platelets. TF = tissue factor; GP = glycoprotein; vWF = von Willebrand’s factor.

membrane a procoagulant surface and provide vari- require carboxylation by vitamin K to become fully
ous types of cellular signaling. Activation of platelets activated. Secondary coagulation is triggered by the
also causes the expression of various glycoproteins same tissue damage that causes platelet adhesion.
including p-selectin and CD40 ligand on the cell Damaged endothelial walls expose tissue factor (TF)
surface and activates the GPIIb/IIIa integrin. The as well as collagen, subendothelial factors, and vWF.
GPIIb/IIIa integrin is the primary surface glycopro- While TF is expressed in endothelial tissues constitu-
tein that attaches to other platelets in the presence of tively, increased amounts of TF are found in inflam-
vWF and causes adhesion (aggregation) of platelets. matory conditions. Additionally, TF is found on
Typically, aggregation also occurs in the presence of monocytes and platelets, especially under pro-
fibrinogen either released from alpha granules or inflammatory conditions, providing a more mobile
created by the secondary coagulation cascade. surface upon which secondary coagulation can
In summary, damaged endothelium has the abil- occur. In more recent literature, microparticles have
ity to grab and hold onto platelets that are passing been described which are blebs of cell membranes
by (adhesion). These platelets in turn become acti- from platelets, monocytes, or other (especially
vated: changing shape, altering the charge on the inflammatory) cells. These microparticles are essen-
cell surface, and releasing their granule contents to tially small traveling pieces of cell membrane that
allow them to aggregate with other platelets and express TF on their surfaces. Microparticles are sig-
create the platelet plug. However, this does not nificant because they provide a possible mechanism
occur by itself but in tandem and simultaneously for the formation of thrombi in tissues distant from
with the secondary coagulation cascade. sites of endothelial damage and are likely a large
player in systemic inflammatory illnesses like sepsis.
The initial phase of the secondary coagulation
Secondary hemostasis
cascade is known as the initiation phase (see Fig.
The secondary coagulation cascade is mediated by 9.3). The goal of the initiation phase is to make a
clotting factors. These clotting factors are produced very small amount of thrombin (factor II) through
by the liver and certain factors (II, VII, IX, and X) two steps. The first step of initiation is to take

Coagulation 179