Clinical Biochemistry of Domestic Animals (Sixth Edition) - UMK ...

II. Mechanisms of Hemostasis
297
FIGURE 10-2 Major components of pro- and
anticoagulant systems. Black lines represent activation
reactions, and red lines represent inhibitory
reactions. Abbreviations: APC, activated protein
C; AT, antithrombin; PC, protein C; PS, phosphatidylserine;
TF, tissue factor; TFPI, tissue factor
pathway inhibitor; TM, thrombomodulin; vWF, von
Willebrand factor.
by strong stimulation of GPIV/FcR γ chain receptors, and
that PECAM-1 does not inhibit GCPR signaling ( Patil
et al ., 2001 ). Consequently, when endothelial damage is
severe enough to expose high concentrations of collagen
and to locally generate thrombin, PECAM-1 will not be an
effective inhibitor of thrombus formation.
C. Coagulation Proteins, Complexes, and
Thrombin Activation
1. Overview
Bleeding from a vessel may be transiently arrested by vasospasm
and platelet plug formation, but the formation of a
thrombus eventually occurs and provides a permanent clot
while repair occurs. The soluble plasma coagulation proteins
are required for formation of the thrombus. Most of
these proteins are made in the liver, but other cells, including
endothelial cells and platelets, are important sources of
additional coagulation factors. Most coagulation proteins
circulate in plasma as inactive zymogens, but when provided
with the appropriate catalyst, they become activated
in a cascade-like manner to ultimately produce thrombin
and then fibrin ( Fig. 10-2 ). Along with a phospholipid surface
provided by activated platelets and calcium as a cofactor,
this series of enzymatic reactions result in cross-linked
fibrin deposition within the platelet plug. Most coagulation
proteins have a Roman numeral designation, which is
followed with an “ a ” when referring to the activated form
(e.g., FVII is the inactive zymogen, whereas FVIIa is the
activated protein). All coagulation proteins additionally
may be referred to by a common or alternate name ( Table
10-5 ). Specific details of the characteristics of individual
factors can be found elsewhere ( Dodds, 1997 ), but details
TABLE 10-5 Coagulation Factors
Traditional
Designation
Factor I
Factor II
Factor III
Factor V
Factor VII
Factor VIII
Factor IX
Factor X
Factor XI
Factor XII
Factor XIII
Prekallikrein
Alternate Name(s)
Fibrinogen
Prothrombin
Tissue factor
Proaccelerin, accelerator globulin
Proconvertin
Antihemophiliac factor
Christmas factor
Stuart factor
Plasma thromboplastin antecedent
Hageman factor
Fibrin stabilizing factor
Fletcher factor
on groups of proteins and how they contribute to blood clot
formation are provided in Section II.C.2.
2. Complexes of the Procoagulant System
a. Tissue Factor-FVIIa Complex
Currently, a single pathway, the tissue factor (TF) pathway,
formerly known as the extrinsic pathway, is considered to be
predominant in the initiation of thrombin formation (see Fig.
10-2 ). TF is a lipid-dependent transmembrane glycoprotein