Vascular Endothelium - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 555

and coagulation factor-XII (Hageman factor). 134 Coagulation factor-XII cleaves
into 2 fragments, one is fixed on the wound edge for molecule adhesion, the
other becomes a peptidase that activates coagulation factor-XI. In turn, coagulation
factor-XIa becomes a peptidase that initiates an activation cascade (Fig. 9.6 ) until
fibrinogen is transformed into fibrin to form a clot. More precisely, coagulation
factor-XII is activated (coagulation factor-XIIa). Activated coagulation factor-
XIIa subsequently converts coagulation factor-XI; coagulation factor-XIa activates
FIX (coagulation factor-IXa). Reacting platelet surface phospholipids accelerate
intrinsic coagulation.
In addition to coagulation factor-XII, thrombin, the final enzyme of the
coagulation cascade, also activates factor-XI (feedback activation). Coagulation
factor-V serves as a cofactor in the activation of coagulation factor-XI by
thrombin [ 1022 ]. Coagulation factor-XI specifically interacts with both coagulation
factor-V and activated coagulation factor-V via multiple binding sites, but not other
cofactors of coagulation, such as activated clotting factor-VIII, high-molecular-
weight kininogen, or protein-S. Depletion of plasma coagulation factor-V and
activated protein-C lower the activation of the intrinsic pathway by thrombin
in plasma.

Extrinsic Pathway

In the extrinsic pathway, coagulation factor-VII is activated in the presence of
calcium by tissue factor (TF), also called platelet tissue factor, coagulation factor-
III, thrombokinase, tissue thromboplastin, or CD142, on plasma membrane surface
or released tissue factor from cell membranes during injury. 135 This glycoproteic
activator resides in the subendothelial layer and in adventitia of blood vessel walls
as well as in platelets and leukocytes. Endothelial cells do not produce tissue factor
when they are not exposed to cytokines such as tumor-necrosis factor-

α

.
Unlike other peptidases that act in the blood coagulation cascade and circulate
as non-functional precursors, tissue factor is a functional initiator when expressed
on cell surfaces. This transmembrane protein possesses an extracellular region that
binds factor-VII and cytoplasmic domain. Binding of coagulation factor-VIIa to
tissue factor can prime signaling for angiogenesis and apoptosis. The activity of the
FVIIa-TF complex is precluded by tissue factor pathway inhibitor via a quaternary
complex TF-FVIIa-FXa-TFPI [ 1023 ].

134 In vitro, activation of the intrinsic pathway can be initiated by coagulation factor-XII on
negatively charged surfaces.
135 In fact, thromboplastin is the combination of both phospholipids and tissue factor that both
trigger the extrinsic pathway. Hence, thromboplastin is an incorrect synonym for tissue factor.