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German Shorthair Pointer
Chesapeake Bay Retriever
129Sv/C57Bl/6J or any



Shetland Sheepdog






Numerous breeds
Scottish Terrier
Dutch Kooiker
RIIIS/J
breed
Table 1.

Species














Mouse








Dog

Pig

Review Article              979



despite a 50-fold excess of molecules of vWf in plasma
compared with FVIII. In type 2 vWd, the level of FVIII
is usually normal except in a particular variant (type
2N) which presents a defective binding of vWf to FVIII
due to point mutations in the vWf gene.
As  a  result  of  the  decrease  of  FVIII  in  vWd,  the
activated partial thromboplastin time may be abnormal.
This assay detects abnormalities in the amplification of
the coagulation cascade, and if the FVIII level is sub-
stantially decreased, the clotting time measured by that
test  is  prolonged.  In  contrast,  assays  such  as  the
prothrombin time, which detects abnormalities in the
extrinsic coagulation pathway, is not affected.



Porcine vWd

A bleeding disorder was described in swine in 1941 by
Hogan  and  colleagues  [39].  Further  studies  demon-
strated  the  similarities  with  human  vWd  such  as  the
prolonged  bleeding  time  and  a  low  FVIII  concentra-
tion,  making  the  vWd  pigs  the  oldest  known  animal
model of a human bleeding diathesis [40–43]. The pig is
a good model of hemorrhagic disorders since its clotting
and platelet characteristics resemble those of humans.
In normal pigs the level of vWf is close to the human
level. Using human plasma as a reference (100%), the
vWf:Ag level in pigs is about 100%, whereas in other
animals such as cow, sheep or goat the levels of vWf:Ag
reach 600–1200% [44].



Clinical evaluation
Bleeding time, measured by ear incision, is prolonged to
more than 10 min in affected pigs, compared with about
2 min in normal pigs [45]. The FVIII level is decreased
to about 30% of wild-type levels (table 1). Interestingly,
pigs have a much higher concentration of various coag-
ulation factors (FV, FVIII, FIX, FXI and FXII) com-
pared with humans. Indeed, the FVIII level in a normal
pig is about 700% compared with human FVIII levels
[45]. The platelet counts were normal in vWd pigs, and
ADP-induced aggregation was not different from that
of  normal  pig  platelets.  Assessments  of  vWf:Ag  and
vWf:RCoF revealed values at the limit of detectability
for the affected pigs, reinforcing the diagnosis of type 3,
severe vWd [43].



Genetic analysis
An extensive study showed that the disease was trans-
mitted as an autosomal recessive trait [46]. The bleeder
swine are homozygous for the defect, whereas the carri-
ers  are  heterozygous.  The  latter  are  usually  asymp-
tomatic, which renders difficult the evaluation of their
980                C. V. Denis and D. D. Wagner



status. Indeed, they don’t have a bleeding tendency and
their FVIII levels are usually normal. However, their
vWf:Ag  and  vWf:RCoF  are  reduced  to  30–40%  of
normal  [43].  It  is  of  interest  to  note  that  in  pigs,  as
opposed to humans, the level of FVIII does not follow
the vWf:Ag very closely. The homozygous pigs are not
totally deficient in vWf. Low, but significant amounts of