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

IV. Disorders of Hemostasis
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of gestation; however, values return to normal by 7 to 14
days postpartum ( Moser et al ., 1998 ). This change is more
notable in normal dogs but does also occur in type I vWD
patients ( Moser et al ., 1998 ). It has been suggested that
this may be a result of rapidly dividing endothelial cells in
a highly vascular placenta ( Moser et al ., 1998 ). In contrast,
there is no significant change in vWF concentration during
the estrus cycle ( Moser et al ., 1998 ). Age can also have
an effect on the vWF concentration, with younger puppies
generally having lower concentrations that gradually
approach mean adult values by 11 weeks of age ( Mansell
and Parry, 1992 ).
In humans, patient response to desmopressin has a positive
correlation with the level of platelet vWF ( Ewenstein,
1997 ). Vasopressin stimulates V2 vasopressin receptors,
resulting in the release of intracellular stores of vWF ( Brooks,
2000 ). A study involving normal dogs and Doberman pinschers
with vWD was conducted in order to assess the effect
of exercise, DDAVP, and epinephrine on vWF concentration
and FVIII activity ( Meyers et al ., 1990a ). The vWF-deficient
dogs were unable to sustain intense exercise for longer than
30 min, whereas the normal dogs were able to complete a
10 km run in 40 min. An increase in FVIII activity was noted
in the normal dogs that was related to the intensity of exercise
and increased blood lactate concentrations, although the
basis for the increase was not clear. vWF increased in these
dogs to a greater extent than FVIII. There was no significant
change in FVIII or vWF concentration in the vWD-positive
dogs. Although their level of exercise was less than that of the
normal dogs, the equivalent exercise was sufficient to cause
an increase in vWF:Ag concentration of 30% in the normal
dogs. The increase in vWF:Ag and FVIII concentrations after
infusion of DDAVP in normal dogs is less than observed in
humans, and some dogs react poorly to this therapy ( Meyers
et al ., 1990a ). In the Meyers et al . study, the vWF:Ag concentration
increased in normal dogs after treatment with DDAVP.
Although the increase noted in the vWF-deficient dogs was
less than 0.1 U/ml, bleeding time decreased in three of six of
these dogs. This finding suggested that DDAVP may induce
the release of the high-molecular-weight (and therefore more
active) forms of vWF; however, Callan et al . (2005) confirmed
through multimer analysis that DDAVP produces an
increase in all multimer sizes. Finally, whereas the vWF:Ag
concentration increased 30 min after administration of epinephrine
in the normal dogs, there was no change in FVIII
activity, nor were there changes in either factor in the vWFdeficient
dogs. Breed variations have also been noted, for
example Airedale terriers tend to have decreased concentrations
of vWF compared to control dogs, yet a history of
bleeding is rare ( Thomas, 1996 ).
2. Platelet Number
Typical clinical signs of thrombocytopenia include petechiae
and ecchymoses, bleeding from mucosal surfaces, and
cutaneous bruising. As mentioned (see Section IV.A.1.a),
with the exception of petechiae, these signs are similar to
those noted in patients with vWD.
Greyhounds and Cavalier King Charles spaniels
(CKCS) have been shown to have lower platelet numbers
when compared to other breeds, without apparent consequence
( Cowan et al ., 2004 ; Sullivan et al ., 1994 ). In addition
to decreased platelet numbers, in 51% of the CKCS
studied, 33% exhibited macrothrombocytes ( Cowan et al .,
2004 ). In fact, the platelet counts in those dogs with macrothrombocytes
were significantly lower than in CKCS
dogs with normal-sized platelets ( Cowan et al ., 2004 ).
The apparent connection between platelet size and number
in these dogs is not surprising based on the association
between platelet mass and TPO concentration (see Section
II.B.1). Although, as mentioned, this platelet anomaly is
benign, there is a decreased platelet aggregation response
to ADP in CKCS ( Cowan et al ., 2004 ).
3. Platelet Function
As noted previously (see Section II.B.2), the GPIIb-IIIa
integrin is essential for platelet aggregation. A deficiency
of this integrin results in thrombasthenic thrombopathia,
also known as Glanzmann’s thrombasthenia. This deficiency
has been identified in humans, dogs (otterhounds
and Great Pyrenees), and horses. Clinical signs of bleeding
in affected canine patients are generally recognized
before 1 year of age and include mucosal hemorrhage,
melena, hematuria, cutaneous ecchymoses, and excessive
surgical bleeding ( Boudreaux and Catalfamo, 2001 ). In
platelet aggregation studies, affected platelets will undergo
shape change but fail to aggregate normally. Abnormal in
vitro clot retraction is also typical of this disease and has
been used as a screening tool; however, this test is not reliable
for identification of carrier animals ( Boudreaux and
Catalfamo, 2001 ). Documentation of decreased or absent
membrane GPIIb-IIIa through flow cytometry or electrophoretic
studies provides a definitive diagnosis. Thus far,
two genetic defects have been identified in Great Pyrenees
dogs, and a single defect in otterhounds ( Boudreaux and
Catalfamo, 2001 ; Lipscomb et al ., 2000 ). Similar to the
dog, equine cases also present with mucosal bleeding,
and they have markedly impaired platelet aggregation and
markedly decreased clot retraction ( Livesey et al ., 2005 ).
A single genetic defect has been identified in the horse and
was consistent between two affected horses of different
breeds ( Christopherson et al ., 2006 ).
Platelet storage pool defects, specifically a deficiency
of dense granules and their contents, result in thrombopathia
in Chediak-Higashi syndrome (CHS). In both cattle
and humans affected with this disease, compared to unaffected
individuals, platelet aggregation was decreased in
response to collagen; concentrations of serotonin, ATP,
and ADP were decreased; and the ratio of ATP:ADP was
abnormally increased ( Bell et al ., 1976 ). Similarly, in CHS
cats, platelet aggregation required considerably higher