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

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Chapter | 10 Hemostasis
proportions as a result of chronic liver failure (i.e. cirrhosis),
suggesting decreased production ( Kerr et al ., 2003 ).
FXI was more notably decreased than the other factors in
chronic liver failure, and FVIII was increased in relation
to the other factors but not in relation to normal patients
( Kerr et al ., 2003 ). The concurrent decreased production
of anticoagulant factors may allow the liver to maintain its
balance between procoagulant and anticoagulant systems,
under stable conditions ( Senzolo et al ., 2006 ).
In some studies of coagulation testing in canine liver
disease, up to 93% of subjects exhibit at least one coagulation
test abnormality ( Badylak et al ., 1983 ). Reports of
the relative frequency of these abnormalities vary, with
some suggesting a higher frequency of prolonged aPTT
( Badylak et al ., 1983 ) and others reporting a higher frequency
of prolonged OSPT ( Badylak and Van Vleet,
1981 ; Toulza et al ., 2006 ). In general, these routine coagulation
tests lack specificity for any given hepatic disease
( Badylak and Van Vleet, 1981 ). Evaluation of specific
factor changes in hepatic disease has demonstrated trends
that may provide more specificity ( Badylak et al ., 1983 ).
For instance, similar to humans, decreased FIX, FX, and
FXI activities have been demonstrated in canine cirrhosis
( Badylak et al ., 1983 ). Coagulation factor trends have also
been identified in canine congenital portosystemic shunts
(CPS). Presurgically there is a decrease in prothrombin,
FV, FVII, and FX, with a concurrent increase in FVIII, and
in the immediate postsurgical period, fibrinogen and FVIII,
FIX, and FXI also decrease ( Kummeling et al ., 2006 ). In
the canine studies, hemorrhagic complications were not
observed; however, more intensive monitoring of potential
bleeding sites in postoperative CPS patients has been
recommended ( Kummeling et al ., 2006 ). In feline studies
of naturally occurring hepatic disease, the frequency
of abnormal coagulation tests varied from 60% to 82%
( Center et al ., 2000 ; Lisciandro et al ., 1998 ). Abnormal
PIVKA and OSPT results were the most frequent coagulation
test abnormalities reported in each study, respectively,
and vitamin K deficiency appeared to be the most common
underlying pathogenesis of the abnormal coagulation tests
( Center et al ., 2000 ; Lisciandro et al ., 1998 ). In the Center
et al . study (2000), only 14% of the cats with liver disease
(representing 23% of those with coagulation test abnormalities)
demonstrated bleeding tendencies. All of the hemorrhagic
signs were associated with clinical procedures (such
as catheterization or venipuncture) rather than spontaneous
episodes ( Center et al ., 2000 ). In the Lisciandro et al . study
(1998), only 1 of 22 cats was reported to exhibit clinically
relevant (and fatal) hemorrhage after a liver biopsy. This
particular patient had coagulation abnormalities consistent
with vitamin K deficiency ( Lisciandro et al ., 1998 ).
Various guidelines exist for prediction of bleeding
based on diagnostic test results in human medicine and
are discussed in Senzolo et al . (2006) . At this time, formal
guidelines have not been developed for domestic animals,
TABLE 10-8 Diseases and Disorders That
Predispose to the Development of Disseminated
Intravascular Coagulation
Condition
Infectious disease/sepsis
Neoplasia
Trauma
Organ damage/failure
Toxic/Immunologic
Etiology
Bacteria, protozoa, fungi,
viruses
Solid tumors, lympho- and
myeloproliferative disease
Tissue damage, burns, fat
embolism
and routine coagulation tests do not appear to consistently
predict the risk of hemorrhage.
4. Disseminated Intravascular Coagulation
Severe pancreatitis, liver failure
Envenomation, transfusion
reactions, immune-mediated
disease
Disseminated intravascular coagulation (DIC) is a potentially
life-threatening hemostatic complication of many serious
clinical diseases and disorders ( Levi, 2004 ). (See Table
10-8 for common precipitating causes in animals.) It is characterized
by systemic activation of the clotting mechanism
that leads to widespread deposition of fibrin in the vascular
tree, to the point of potentially compromising blood flow to
tissues and causing ischemic damage and even organ failure.
Concurrently, platelet and clotting factor supply becomes
depleted as a result of widespread thrombus formation, and
subsequent hemorrhage may occur. Although it may seem
paradoxical and complicates management, a patient with
DIC can be presented with clinical signs of both thrombosis
and bleeding simultaneously.
The pathogenesis of DIC varies with the underlying
primary disease process, and much of the understanding of
how the process develops comes from human and animal
sepsis models. It appears that either a systemic inflammatory
response or release of procoagulant materials into the
vascular space can activate coagulation on a widespread
basis ( Levi, 2004 ). The simultaneous development of
increased thrombin generation, suppressed anticoagulant
mechanisms, impaired fibrinolysis, and activation of the
inflammatory response provide all the factors necessary for
the syndrome to occur ( Franchini et al ., 2006 ).
Cell membrane components of organisms (such as endotoxin
and lipopolysaccharide) or bacterial exotoxins cause a
generalized inflammatory response resulting in elaboration
of proinflammatory cytokines that can activate endothelial
cells directly (Slofstra, 2003). Excessive generation of