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

Chapter 10
Hemostasis
Patricia Gentry
Department of Biomedical Sciences
Ontario Veterinary College
University of Guelph
Guelph, Ontario, Canada
Hilary Burgess
Department of Pathobiology
Ontario Veterinary College
University of Guelph
Guelph, Ontario, Canada
Darren Wood
Department of Pathobiology
Ontario Veterinary College
University of Guelph
Guelph, Ontario, Canada
I. INTRODUCTION
II. MECHANISMS OF HEMOSTASIS
A. Role of Vascular Endothelium
B. Platelets
C. Coagulation Proteins, Complexes, and Thrombin
Activation
D. Fibrinolysis
III. LABORATORY ASSESSMENT OF HEMOSTASIS
A. Quality Control and Reagent Variation
B. Routine Testing of Hemostasis
C. Additional Assays
IV. DISORDERS OF HEMOSTASIS
A. Hereditary Disorders
B. Acquired Disorders
V. BEYOND HEMOSTASIS: INTERACTIONS WITH
INFLAMMATION
REFERENCES
I. INTRODUCTION
The maintenance of blood fluidity occurs through the
process of finely balancing hemorrhage and clotting.
Hemostasis, which is the process of arresting the escape of
blood from the vascular system, is integral to survival in
animals, is regulated by a series of orchestrated events, and
is dependent on the vessels through which blood flows,
as well as numerous proteins (coagulation factors, inhibitors,
and fibrinolytic proteins) and cells (platelets, endothelial
cells, and monocytes predominantly). Other systems
in the body are also closely related to blood clotting and
influenced by the activation of hemostasis such as the
innate immune system (complement and phagocytes) and
the inflammatory response (the kinin system and the cells
important for hemostasis). The stepwise process that takes
place to minimize blood loss and repair the injury includes
(1) initial vasospasm, (2) platelet activation and plug formation,
(3) assembly and activation of the coagulation cascade
factors, (4) fibrin clot formation at the site of injury,
and (5) dissolution of the clot and vascular repair. Each of
these processes is described in more detail in the discussion
that follows.
Numerous reviews are available that describe the hemostatic
process in detail ( Crawley et al ., 2007 ; Hoffman
and Monroe, 2007 ; Hopper and Bateman, 2005 ; Sere and
Hackeng, 2003 ). The goals of this chapter are to review the
comparative biochemistry of hemostasis and to describe
how the dramatic variations in blood clotting in different
species impact laboratory testing, response to therapeutic
agents, downstream effects on other body systems, and the
array of diseases that can occur.
II . MECHANISMS OF HEMOSTASIS
A. Role of Vascular Endothelium
Endothelial cells that line the lumen of blood vessels are
the principal components of the vessel wall that contribute
to maintenance of the fluid state of blood during health and
the formation of clots during vascular compromise. Besides
serving as a direct barrier between blood and tissue, these
cells are actively involved in the regulation of hemostasis,
inflammation, host defense, and numerous metabolic reactions.
The phenotype of endothelial cells varies throughout
the body, so the importance of these functions in different
parts of the vascular system also varies. The endothelium
exhibits plasticity with respect to hemostasis in that
it is the balance of pro- and antithrombotic mediators that
determine whether normal blood flow, hemorrhage, or
clot formation occurs ( Table 10-1 ). Unregulated or widespread
activation of endothelial cells can have drastic consequences,
as observed with disseminated intravascular
coagulation (DIC).
Clinical Biochemistry of Domestic Animals, 6th Edition 287
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