Coagulation
Coagulation is a complex process by which
blood forms clots. It is an important part of
hemostasis (the cessation of blood loss from
a damaged vessel), wherein a damaged blood
vessel wall is covered by a platelet and fibrin-
containing clot to stop bleeding and begin re-
pair of the damaged vessel. Disorders of co-
agulation can lead to an increased risk of
bleeding
(hemorrhage)
or
clotting
(thrombosis).
Coagulation
is
highly
conserved
throughout biology; in all mammals, coagula-
tion involves both a cellular (platelet) and a
protein (coagulation factor) component. The
system in humans has been the most extens-
ively researched and, therefore, the best-
understood.
Coagulation begins almost instantly after
an injury to the blood vessel has damaged the
endothelium (lining of the vessel). Platelets
immediately form a plug at the site of injury;
this is called primary hemostasis. Secondary
hemostasis occurs simultaneously: Proteins
in the blood plasma, called coagulation
factors or clotting factors, respond in a com-
plex cascade to form fibrin strands, which
strengthen the platelet plug.[1]
Physiology
Platelet activation
Damage to blood vessel walls exposes
subendothelium proteins, most notably colla-
gen, present under the endothelium. Circu-
lating platelets bind collagen with surface
collagen-specific glycoprotein Ia/IIa recept-
ors. The adhesion is strengthened further by
the large, multimeric circulating proteins von
Willebrand factor (vWF), which forms links
between the platelets glycoprotein Ib/IX/V
and the collagen fibrils. This adhesion activ-
ates the platelets.
Activated platelets release the contents of
stored granules into the blood plasma. The
granules include ADP, serotonin, platelet-ac-
tivating factor (PAF), vWF, platelet factor 4,
and thromboxane A2 (TXA2), which, in turn,
activate additional platelets. The granules’
contents
activate
a Gq-linked
protein
receptor cascade, resulting in increased cal-
cium concentration in the platelets’ cytosol.
The calcium activates protein kinase C,
w