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Canine Von Willebrands Disease

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von Willebrands Disease
von Willebrand's Disease (vWD)

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von Willebrand's Disease
(vWD)

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What is von Willebrand's disease?
Von Willebrand's disease (vWD) is a common, usually mild, inherited bleeding disorder in people and in dogs. It is caused by a lack of von Willebrand factor (vWF), which plays an essential role in the blood clotting process.

Normally the body responds to an injury causing bleeding through a complex defence system. This consists of local changes in the damaged blood vessels, activation of blood cells called platelets, and the coagulation process. A reduction in von Willebrand factor leads to abnormal platelet function and prolonged bleeding times. Affected dogs are prone to bleeding episodes such as nose bleeds, and generally experience increased bleeding with trauma or a surgical procedure.

Three forms of the disease are distinguished based on vWF concentration and function. Dogs with Type I vWD (by far the most common) have mild to moderate bleeding abnormalities, depending on the level of vWF. The much rarer types II and III vWD cause severe bleeding disorders.

How is von Willebrand's disease inherited?
The most common form (Type I vWD) is thought to be an autosomal trait with incomplete dominance. This means offspring may inherit the disorder if either parent carries the gene, but not all offspring will be affected to the same extent. Dogs with type I disease have reduced but measurable levels of Von Willebrand factor (1 to 60 per cent). Animals that inherit the gene for type I vWD from both parents (homozygotes) die before birth or shortly thereafter.

Type III vWD is relatively rare. This form is autosomal recessive. Animals are only affected if they inherit the abnormal gene from both parents, who are clinically unaffected carriers. Affected dogs have zero levels of vWF, while carrier parents have 15 to 60 per cent of normal levels.

Type II vWD is very rare. It is an autosomal recessive trait.

Bleeding abnormalities are severe in dogs with Types II and III von Willebrand's disease.

What breeds are affected by von Willebrand's disease?
Type I vWD: This is by far the most common form. The gene for the condition is widespread in the Doberman pinscher population, and is also relatively common in the Scottish terrier and Shetland sheep dog.  There is an increased risk of the disorder in the Golden retriever, standard and miniature poodle, Welsh Pembroke corgi, miniature Schnauzer, basset hound, German shepherd, Rottweilers, Manchester terrier, Keeshond, and standard and miniature dachshund. This disease occurs in most other breeds and in mixed-breed dogs as well.

Type III vWD: rare, occurs in the Scottish terrier, Shetland sheepdog, and very sporadically, in the Chesapeake Bay retriever

Type II: extremely rare, German short-haired pointer 

For many breeds and many disorders, the studies to determine the mode of inheritance or the frequency in the breed have not been carried out, or are inconclusive. We have listed breeds for which there is a general consensus among those investigating in this field and among veterinary practitioners, that the condition is significant in this breed.

What does von Willebrand's disease mean to your dog & you?
Although many dogs are affected by vWD, only a small proportion have severe problems.  Dogs with vWD are prone to nose bleeds, bleeding from the gums, and prolonged bleeding during heat or after whelping. There may be prolonged bleeding from the umbilical cord at birth or when your pup sheds its baby teeth. Excessive bleeding after surgery or trauma is common, and may be the first sign of this condition in your dog. You may see blood in your dog's urine or stool.

Most dogs with vWD can lead normal lives, with occasional bleeding episodes that may go unnoticed or can be treated appropriately. Other illnesses, or physical or emotional stress may worsen bleeding episodes. In affected dogs, it is best to consult your veterinarian before using any over-the-counter medications. Drugs such as aspirin for example, alter the function of platelets, and should be avoided in dogs with bleeding disorders.

How is von Willebrand's disease diagnosed?
Because the severity of bleeding with von Willebrand's disease is quite variable, often the disease is not diagnosed until the dog is 3 to 5 years old. Your veterinarian may suspect vWD because of a history of abnormal bleeding in your dog, such as unexplained nosebleeds, or there may be heavy bleeding during surgery. Stillbirths or pups that die shortly  after birth ("fading puppies'') may be a result of both parents being carriers of the gene for von Willebrand's disease.  

There are specialized tests available to make the diagnosis of von Willebrand's disease. One is a genetic test and the other measures blood levels of von Willebrand factor.

FOR THE VETERINARIAN:
Mucosal bleeding time is the best screening test for a potential defect in platelet function, and is prolonged in dogs with a deficiency in vWF. However the test is non-specific for vWD because it is also prolonged in dogs with thrombocytopenia or functional platelet defects. (Bleeding times are normal in animals with warfarin toxicity, hemophilia A or B, or a deficiency of Factor VII.)

Specific diagnosis of vWD requires either genetic testing in those breeds in which it is available, or vWF measurement. The genetic test is performed by submitting a sample (such as a mucosal scraping) to a genetic testing laboratory. The   results are reliable at any age. Measurement of vWF:Ag levels is done by electroimmunoassay or enzyme-linked immunoabsorbent assay (ELISA). Samples for testing must be submitted to the diagnostic laboratory very fresh in a citrate tube (within 1 to 2 hours of collection). Where this isn't possible, the blood sample should be separated immediately after collection and the plasma submitted frozen. It is best to check with your diagnostic laboratory for shipping instructions. VWF levels vary between breeds and with respect to age.

Because of the possible link with hypothyroidism,  thyroid status should be evaluated.

How is von Willebrand's disease treated?
This condition cannot be cured but it can be managed. Your veterinarian will discuss this with you when the diagnosis is made.

You will likely be able to control mild bleeding yourself by applying prolonged pressure. In other circumstances, veterinary care such as cautery or sutures may be required. Severe bleeding episodes are treated by administering a source of von Willebrand factor through a transfusion. If your dog requires surgery, your veterinarian may recommend a transfusion pre-operatively as a precaution, depending on the severity of the bleeding disorder, and the type of surgery.

Thyroid supplements may help to control bleeding, if your veterinarian determines that your dog is hypothyroid.

FOR THE VETERINARIAN:
Exogenous vWF may be supplied through administration of fresh whole blood, fresh or fresh-frozen plasma, or cryoprecipitate (treatment of choice).

Where possible, avoid the use of drugs that have been known to cause thrombocytopenia or otherwise affect platelets. Such drugs include NSAIDs (aspirin, phenylbutazone, ibuprofen, indomethacin), some antibiotics (penicillin, sulfonamides, ampicillin, chloramphenical), antihistamines, phenothiazines, theophylline,heparin, and estrogen.

Some studies have shown that thyroid supplementation in euthyroid dogs can reduce bleeding, but other studies have contradicted this.

Genetic counselling
The trait for von Willebrand's disease is widespread, particularly in Doberman pinschers but also in several other breeds. An accurate genetic test has been developed for the Doberman pinscher, Scottish terrier, Shetland sheepdog, Manchester terrier, poodle, and Pembroke Welsh corgi. Testing can reliably identify dogs with vWD, dogs that are carriers, or dogs that are clear (see reference below for information on testing). 

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. These dogs have reduced levels of vWF (25 to 60 per cent) but do not have bleeding problems. Levels vary with age and between breeds. Where a bleeding disorder has been identified, breeders are advised to test breeding stock. Dogs with von Willebrand's disease and those who are carriers should not be used for breeding.

Where to find more information?
deGopegui, R.R. and Feldman, B.F. 1998.Acquired and inherited platelet dysfunction in small animals.Compendium on Continuing Education for the Practicing Veterinarian 20:1039.
Brooks, M. 1996. Emergency management of canine von Willebrand's disease. A.C.V.I.M. Proceedings of the 14th Annual Vet. Medical Forum.34.
http://www.vetgen.com  - information on genetic testing available

Copyright © 1998 Canine Inherited Disorders Database. All rights reserved.
reprinted with kind permission from:-
 Alice Crook, DVM,Coordinator, Sir James Dunn Animal Welfare Centre, Atlantic Veterinary College,University of Prince Edward Island, 550 University Ave.Charlottetown, PEI C1A 4P3
http://www.upei.ca/cidd

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THE PET HEALTH LIBRARY

By Wendy C. Brooks, DVM, DipABVP
Educational Director, VeterinaryPartner.com 
http://www.VeterinaryPartner.com

Von Willebrand's Disease

Most people are familiar with hemophilia A, an inherited blood clotting defect in human beings affecting only male children. Most people, however, are not as familiar with von Willebrand's disease and hear of it for the first time when they ask questions about breeding their dog. Von Willebrand's disease is also an inherited blood clotting defect and breeds at high risk should be screened before being allowed to breed.

What Is von Willebrand's Factor?
Von Willebrand's factor is a glycoprotein produced both by platelets (the blood cells involved in clotting) and by the cells lining blood vessels. It is made up of several smaller proteins bound together and von Willebrand's disease results when there is a defect in any of these proteins. When a blood vessel tears and bleeding occurs, platelets are called to the area to clump upon each other thus plugging up the hole and staunching the bleeding. While the platelets are in place, a cascade of blood clotting factors activates ultimately leading to production of "fibrin," the material scars are made from, to more permanently seal the vessel. Von Willebrand's factor acts as glue holding the platelets together and holding them onto the surface of the torn blood vessel. Von Willebrand's factor also serves to stabilize "clotting factor VIII," one of the proteins involved in forming the fibrin clot.

When there is something wrong with one's von Willebrand's factor, platelets to do not stick together properly and inappropriate prolonged wound bleeding occurs.

Types of Von Willebrand's Disease
There are three types of von Willebrand's disease. In Type I, all the proteins making up von Willebrand's factor are present but they are present in very low amounts. This is the type common in the Doberman pinscher, the Shetland sheepdog, the German Shepherd dog, and the Standard Poodle. In Type II, the larger proteins making up von Willebrand's factor are completely absent. This creates more severe bleeding episodes and represents the type of von Willebrand's disease usually seen in German short-haired and wire-haired pointers. In Type III von Willebrand's, there is simply no von Willebrand's factor at all. This is the most severe form and is usually seen in Scottish terriers, Chesapeake Bay retrievers, and Shetland sheepdogs. Von Willebrand's disease is not limited to the breeds listed here; forms of von Willebrand's disease have been found in over 50 breeds and in cats and humans as well.

Unlike the genetics of Hemophilia A in humans, which is reviewed in detail in virtually every high school biology class as a sex-linked recessive trait, von Willebrand's disease is not as simple. Males and females are equally affected and the inheritance seems to be recessive but complicated.

Diagnosis of Von Willebrand's Disease: Blood Testing and DNA Testing
Classically, testing for von Willebrand's disease is accomplished by measuring von Willebrand's factor in a blood sample. The amount of factor in the patient's serum is compared to that found in "normal" dogs. The patient's results are compared to the normal and expressed in a percentage (thus it is possible for a patient to have greater than100% as their result).

Normal is considered to be 70% to 180%.

Borderline is considered to be 50% to 69%.

Abnormal (affected or genetic carrier) is considered to be less than 49%.

Though these results in part depend on the laboratory running the test. Dogs in the abnormal group are at risk for bleeding and should definitely not be bred. 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, so 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 von Willebrand's disease is present, and further testing by a technique called electrophoresis is needed to do this if one is interested. Knowing the type of von Willebrand's disease is unlikely to change therapy, thus testing is not commonly done.

DNA testing is currently available for, at the time of this writing, 11 breeds through a company called VetGen (www.vetgen.com). 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 validity of genetic test has not been independently published and remains controversial.

A simple screening test often done before a surgery is a bleeding time. A small wound is created in the mouth using a spring-loaded blade created just for this purpose (a Symplate Device). The time required for clotting to occur is measured and should be under 4 minutes or so. The patient is generally under anesthesia at this point. The test has previously been accomplished by clipping a toenail short and inducing bleeding but this technique has largely been abandoned as it cannot be standardized. Bleeding times are tests of platelet function in general and are not specific for von Willebrand's disease.

Suddenly Symptoms?
One would expect a congenital disease like von Willebrand's disease to manifest in puppyhood and in fact this is usually so. Von Willebrand's disease is usually detected when there is unexpected hemorrhage during a spay or neuter or when screening tests are done in anticipation of surgery on a member of a von Willebrand's breed. Sometimes a dog with borderline von Willebrand's factor will have a slight drop in platelet function as occurs with vaccination or with treatment with a non-steroidal anti-inflammatory drug, and will experience inappropriate bruising or bleeding transiently. This is something that might be seen later in life.

Treatment of the Affected Dog
When hemorrhage is occurring or is anticipated (as with a planned surgical procedure), the best treatment is administration of von Willebrand's factor. Pure von Willebrand's factor cannot be purchased by a blood product called cryoprecipitate that is particularly rich in von Willebrand's factor is the best transfusion choice. Complete plasma is the next best choice and is much more available than cryoprecipitate. Administration of cryoprecipitate improves bleeding time for approximately 4 hours after administration.

A hormone called DDAVP (or desmopressin acetate) can be helpful as its use seems to cause a sudden release of von Willebrand's factor into the bloodstream. There may be other helpful blood clotting benefits to this treatment as in dogs the release of von Willebrand's factor is not as great as it is in humans but despite this the bleeding time is still shortened for approximately 2 hours after the 30 minute onset period after DDAVP injection.

One of the most important lessons to learn regarding von Willebrand's disease is not to breed
untested members of von Willebrand's breeds
(and one could argue for the testing of any dog to be bred).

Breeds routinely tested are Doberman Pinscher, Golden Retriever, Shetland Sheepdog, Rottweiler, Schnauzer, German Shepherd Dog, German Short-Haired Pointer, Standard Poodle, and Scottish Terrier.
Copyright 2004 - 2007 by the Veterinary Information Network, Inc. All rights reserved.
This work was originally published by Veterinary Information Network, Inc. (VIN)
and is republished with VIN's permission.

vWD


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The above information is simply informational. It's intent is not to replace the advice of a veterinarian nor to assist you in making a diagnosis of your pet. Please consult with your own veterinarian for confirmation of any diagnosis. Your pets life may depend on it.