Vascular Endothelium - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 550

9.8.1 Blood Coagulation

Blood hemostasis, i.e., cessation of blood loss from an injured vessel, results
from changes in blood flow pattern, vessel wall, and thrombogenic potential.
Blood coagulation corresponds to the latter component of blood hemostasis. Blood
coagulation begins immediately after an injury has damaged the endothelium.
Plasmatic coagulation factors, or clotting factors, are involved in a complex reaction
cascade to form a fibrin mesh that strengthens the platelet aggregate fixed onto the
evolving, responsive vessel wall matrix.
Upon vascular injury, intracellular materials from damaged cells are released
and thus exposed to blood components. Extracellular RNA can promote blood
coagulation [ 1010 ]. It increases the activation of peptidases of the contact pathway
of blood coagulation, such as factor-XII and -XI. von Willebrand Factor (vWF)
is able to stop bleeding under high flow [ 1011 ]. The reversible unfolding of this
glycoprotein extends its length up to 100

m, thereby yielding a sufficient density
of binding sites for collagen. Moreover, this conformational change occurs in a very
short time. The strong increased probability of bound von Willebrand factor favors
the formation of a mesh for platelet adhesion.
When the blood vessel wall, especially the endothelium, is damaged, blood must
clot to halt bleeding. The coagulation cascade takes place at the site of vessel wall
gap where platelets aggregate (Fig. 9.6 ). Blood clotting involves circulating platelets
that are able to clump. Complete aggregation requires the release of adenosine
diphosphate (ADP) and other mediators from dense granules and stimulation of
P2Y 12 receptors. Among Rab GTPases that regulate vesicular transport during both
endo- and exocytosis (Vol. 1 - Chap. 9. Intracellular Transport), Rab27 regulates the
secretion of dense granules by platelets [ 1012 ].
The hemostatic process depends on stable adhesion and aggregation of platelets
with constituents of the subendothelial matrix at the vessel injury site. Several
clotting factors are required (Table 9.28 ). Endothelial cells synthesize coagulation
factors, von Willebrand factor, and tissue factor that activates FVII.
The coagulation cascade is primed by blood vessel injury to produce a solid fibrin
clot to cover the damaged blood vessel and stop hemorrhage. A blood clot is made
of a branched scaffold of fibrin fibers stabilized by factor-XIIIa, platelet aggregates,
and trapped erythrocytes.
Plasma fibrin precursor — fibrinogen — is converted by cleavage into fibrin.
Fibrin monomers polymerize to form the fibrin clot, a gel generated by a network of
fibers attached by crosslinks. Fibrin clot is associated with aggregation of platelets
to form a plug that blocks the orifice across the blood vessel wall, thereby quickly
restricting blood leakage before stopping bleeding.
The fibrin clot is a viscoelastic polymer. A blood clot needs to have suitable
stiffness to obstruct the mural breach and remodeling capacity to remain degradable
by enzymes to avoid thrombi and emboli. Changes in calcium level and pH can
affect fibrinogen springiness. Fibrin fibers can be strained 180% (2.8-fold extension)
without sustaining permanent lengthening and up to 525% (average 330%) before
rupturing [ 1013 ]. Fibrin fibers are much stiffer for stretching than for flexion. Elastic