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Von
Willebrand’s Disease
Von Willebrand’s,
disease, abbreviated vWD, is not so much a disease as a disorder.
Of all the inherited bleeding disorders in animals and humans (Yes,
humans have vWD.), it is the most prevalent. Many associate vWD
with the Doberman breed, but it has been found in over 50 breeds,
mixed breeds and in cats, pigs, rabbits and humans as well. Yes,
vWD has been reported in Bichons.
When a blood
vessel is torn and bleeding occurs, platelets are called to the area
to clump upon each other thus plugging up the hole and staunching
the bleeding. When the platelets are in place, a series of factors,
factor I, II, III and so on, begin a cascading process to stop the
bleeding and produce “fibrin”, the material scars are made of, to
more permanently seal the vessel. Von Willebrand’s factor (factor
VIII), abbreviated vWF, is made up of several proteins bound
together and is the glue that holds the platelets together. When
factor VIII is low or there is a defect in any of the proteins
making up factor VIII, the fibrin that holds platelets together and
onto the surface of the torn blood vessel does not stabilize the
clot and prolonged bleeding occurs.
Inheritance
Von Willebrand’s
disease occurs as three types. In Type I vWD, the most common form,
all the proteins making up vWF are present and normal but vWF is
present in very low amounts. Type I vWD is thought to be an
autosomal trait with incomplete dominance. Males and females with
one abnormal gene are carriers of vWD trait and on average they will
transmit the abnormal gene to one-half of their offspring. All
offspring who inherit the abnormal gene from either parent are
carriers, but not all offspring will be affected to the same
extent. In most breeds, the presence of one abnormal gene is
sufficient to cause a bleeding tendency from mild to severe.
Animals that inherit the gene for Type I vWD from both parents die
before birth or shortly thereafter. This is the type common in the
Doberman Pinscher, the Shetland sheepdog, the German Shepherd dog,
and the Standard Poodle.
In Type II vWD,
the larger proteins making up vWF factor are abnormal and vWF is low
creating more severe blooding problems than Type I. It is an
autosomal recessive trait and is very rare. Type II is seen in
German short-haired and wire-haired pointers.
In Type III vWD,
von Willebrand’s factor is low or absent and proteins are absent.
All pups die before birth or shortly after. This relatively rare
and severe form is usually seen in Scottish terriers, Chesapeake Bay
retrievers, and Shetland sheepdogs.
Diagnosis
Because the
severity of bleeding is quite variable with vWD, often the disease
is not diagnosed until the dog is three to five years old. The most
common signs of vWD are spontaneous bleeding from the gums or nose,
blood in the urine or gastrointestinal tract (which may cause the
stool to either have blood in it or be black and tarry), or
excessive bleeding after clipping nails. Excessive bleeding may be
noted after tail docking or surgery such as spaying or castration.
Bleeding into joints may also occur causing symptoms similar to
those of arthritis. Prolonged bleeding after estrus (heat) cycles
or after pregnancy may indicate vWD.
Mucosal bleeding
time is a screening test for a potential defect in platelet
function, and is prolonged in dogs with a deficiency in von
Willebrand’s factor. However, the test is non-specific for vWD
because it is also prolonged in dogs with thrombocytopenia or
functional platelet defects. Because a breed commonly affected with
vWD is bleeding excessively doesn’t mean it is vWD. On the reverse,
because a breed is not usually associated with vWD, it cannot be
ruled out as a cause for the bleeding. A blood workup is always in
order and this usually entails general blood work as well as
specific clotting functions.
There are two
tests, Von Willebrand factor antigen (vWF:Ag) test and DNA test,
specific for vWD. The level of vWF in a test plasma sample is
measured and then reported as a percentage compared to standard
control plasma. This testing should be done at an early age since
the disorder often diminishes with age, causing false-negative test
results in older animals. In addition, a dog may test differently
on different days, when blood is drawn from different veins, when
the dog is more excited, or if the dog is pregnant. It may be
necessary to test a dog several times before being comfortable with
the result. This type of testing does not indicate what Type of vWD
is present. A technique called “electrophoreses” is needed to do
this although knowing the Type of vWD is unlikely to change
therapy. The vWF:Ag measurement is used as a predictor of a
dog’s genetic status for the vWD trait. A dog testing in the normal
range (70 – 180%vWF:Ag%) is considered clear of vWD trait, and at
low risk for expressing or transmitting the vWD trait. A dog
testing in the borderline range (50 – 69%vWF:Ag%) cannot be
accurately classified as a carrier or clear of the trait on the
basis of that measurement. This is an overlap region plasma vWF:Ag%,
where some individuals are clear and some carriers of vWD. A dog
testing in the abnormal range
(0 -49%vWD:Ag%)
is considered a carrier of the vWD trait and is at risk for
transmitting abnormal vWF gene to its offspring, and in some
individuals, for expressing an abnormal bleeding tendency. The
vWF:Ag% alone cannot differentiate asymptomatic carriers from
“bleeders” in most breeds.
DNA testing is
currently available for, at the time of this writing, 11 breeds
through a company called VetGen. A swab of the inside of the
patient’s mouth is all that is required to determine whether the dog
is clear, a carrier, or affected. The VetGen test is 100% accurate
for vWD in Scottish Terriers but their accuracy for other breeds has
not been published. This test can be done while pups are still in
the whelping box thus determining those clear of the abnormal gene
and those that are carriers.
Different breeds
exhibit different variations of the disease, and some individual
animals appear to “acquire” vWD. Sometimes a dog with borderline
vWF will have a slight drop in platelet function as occurs with
vaccination or with treatment with a non-steroidal anti-inflammatory
drug, hormones and certain antibiotics, and will experience
inappropriate bruising or bleeding transiently. This is something
that might be seen later in life. In some dogs, abnormal bleeding is
only seen after surgery or trauma. Concurrent stress conditions
such as viral and bacterial infections, hormonal fluctuations
associated with heat cycles or pregnancy, and endocrine disorders
causing deficiencies of steroid or thyroid hormone can all
exacerbate signs of hemorrhage in dogs affected with vWD.
Researchers also believe vWD may be caused by an autoimmune
disorder, (http://www.bichonhealth.org/HealthInfo/Hemolytic.asp) in which the body’s own immune system
attacks the blood system. Exactly what triggers “acquired” vWD is
not known. A genetic factor may increase the risk of developing
it.
Management
Von Willebrand’s
disease cannot be cured but it can be managed. Applying prolonged
pressure to a wound is likely to control mild bleeding. In other
circumstances, veterinary care such as cautery or sutures may be
required. When hemorrhage is occurring or is anticipated (as with a
planned surgical procedure), the treatment of choice is transfusion
of cryoprecipitate which is rich in von Willebrand’s factor.
Complete plasma is the next best choice and is much more available
than cryoprecipitate. Where possible, avoid the use of drugs that
have been known to cause thrombocytopenia (http://www.bichonhealth.org/HealthInfo/Thrombocytopenia.asp) or otherwise
affect platelets. Such drugs include non-steroidal
anti-inflammatory drugs (aspirin, Rimadyl, phenylbutazone,
ibuprofen, indomethacin), some antibiotics (penicillin,
sulfonamides, ampicillin, chloramphenical), antihistamines,
phenothiazines, theophylline, heparin, and estrogen.
Some studies have
been done which suggest a drug called desmopressin acetate (DDAVP)
may help dogs with bleeding episode. The drug can be administered
transnasally (into the nose) to increase clotting. There is still
some controversy over whether this treatment is effective.
Some studies have
shown hypothyroid dogs with vWD have benefited from thyroid
supplementation, but other studies have contradicted this showing
increased bleeding.
Summary
The good news is
with genetic testing, affected carriers can be eliminated from a
breeding program. In breeds where specific genetic tests are not
yet available, carriers of the trait can still be identified through
the blood test for von Willebrand factor. The link between vWD and
autoimmune disorders is yet to be discovered. Until then, breeders
and owners should be ever mindful of effects of vaccines, drugs and
outside chemicals on the immune system.
For Bichon Frise
breeders, the likelihood of vWD is rare. However, the possibility
is very real, therefore any bleeding disorder in a Bichon Frise
should be thoroughly investigated. If vWD is suspected, the owner
of the sire, dam and all genetic relatives should be notified with
the hope that all would be tested. It is the responsibility of all
breeders to protect against all inherited diseases.
http://en.wikipedia.org/wiki/Cryoprecipitate
http://www.ggc.org/glossary.htm
http://www.moonstruckmeadows.com/vonWillebrands.htm
http://www.upei.ca/~cidd/Diseases/clinical%20pathology/von%20Willebrand's%20disease.htm
http://www.angelfire.com/nc/meisenhaus/vwd.html
http://www.peteducation.com/article.cfm?cls=2&cat=1614&articleid=488
http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/10608.htm&word=Von%2cWillabrand%2cdisease
http://www.veterinarypartner.com/Content.plx?P=A&S=0&C=0&A=1637
http://healthlink.uhseast.com/library/healthguide/en-us/support/topic.asp?hwid=uh1407
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