Von Willebrand’s Disease

Von Willebrand’s Disease in Italian Greyhounds

Linda Layne, Nancy Gress-Hall & Lonnell Crawford

 

What is von Willebrand’s disease?
Von Willebrand’s disease (vWD) is the most common inherited bleeding disorder in dogs. Affected dogs have a defective form of a protein that helps platelets form clots. This protein is called von Willebrand’s Factor (vWF). Due to the ineffectiveness of their vWF, affected dogs may have excessive bleeding upon injury or emotional stress.

Not Knowing
As conscientious breeders, we began our breeding programs with what we believed to be healthy dogs free of genetic diseases. Little did we know, a potentially lethal recessive gene for vWD was present in the background of our Italian Greyhounds.

How We Found Out
We recently learned that a puppy from our bloodlines had suffered unexplained bleeding after scratching at its ear. The owner had her tested and the puppy was determined to have vWD. In retrospect, several incidences of bleeding in our own dogs became focused in a new light. What veterinarians had believed to be sensitive stomachs (gastro-intestinal upsets) colitis, or gastro-enteritis turned out to be possible symptoms of vWD. Recently, one of the older affected dogs died after an episode of intestinal bleeding.

What Are The Symptoms?
Symptoms of vWD can include any of the following:
• Hemorrhagic diarrhea (bloody stools)
• Hematuria (blood in the urine)
• Recurrent shifting lameness from bleeding in the joints
• Bleeding from gums, noses, ears, vagina or penis
• Prolonged bleeding when nails are trimmed too short
• Prolonged estrus, excessive or lengthy bleeding after whelping
• Still births with evidence of hemorrhage (puppies will exhibit excessive cord bleeding or may have a blue color in the abdominal area
• Hematomas or blood blisters resulting from minor injury
• Severe bleeding from even minor surgery

Affected dogs may have a history of routine surgery (spay or neuter) with no complications, but then later in life have bleeding episodes.

What Did We Do?
It was discussed and decided among us that it was imperative to begin vWD testing immediately. We submitted blood samples from all our dogs to be tested for the level of vWF. We were saddened and dismayed to learn that several of our dogs had very low levels of vWF, which indicated that they were affected with the disease.

In an effort to find some good in this situation, we submitted DNA from all the affected dogs to VetGen, a DNA testing laboratory. VetGen currently has DNA tests for two types of vWD known to affect 10 different breeds of dogs. It was our hope that our DNA samples might lead to the identification of a specific genetic marker for vWD in Italian Greyhounds. None of the known DNA tests are applicable to IG’s but work in this area is ongoing.

What Can You Do?
IG breeders and owners can help reduce or eliminate this disease by testing their breeding stock and related dogs. Any dogs that are determined to have vWF level of 25% or less (compared to a normal dog) can aid in the search for a DNA marker.

If you have vWD tested your dogs, share that information with the fancy. Submit test results to the IGCA’s pedigree database. 

A Little More About von Willebrand’s Disease

Teri Dickinson DVM

Von Willebrand’s disease (vWD) was first recognized in humans, but is now known to be the most common inherited bleeding disorder in dogs.

Von Willebrand’s disease is caused by the production of defective von Willebrand’s factor (vWF) a protein used in the blood clotting process. While all vWD is due to insufficient amounts of normal vWF, three types of vWD are known to exist.

Type I is the most common form of vWF, affecting Bernese Mountain Dogs, Doberman Pinschers, Kerry Blue Terriers, Manchester Terriers, Pembroke Welsh Corgis, Poodles and Papillons. Many other breeds including IGs have vWD which clinically appears to be Type I but this has yet to be proven with DNA testing.

Dogs affected with Type I vWD have a mutation which allows normal vWF to be produced part of the time, so even dogs with two copies of the defective gene (affected dogs) have some minimal amount of normal vWF. Carriers, which have one normal gene and one affected gene, have a moderate amount of normal vWF and dogs which are clear have two normal genes and have normal levels of vWF.

Despite the fact that many Type I affected dogs have very low levels of normal vWF, not all exhibit signs of bleeding. Conversely, carriers may have moderate levels of vWF and still exhibit prolonged bleeding times. More information about Type I vWD can be found at http://www.vetgen.com/vwddobs.html.

Type II vWD affects German wire and short haired pointers. Type IIII vWD occurs in Shelties and Scottish Terriers. Dogs affected with Type III vWD have very little normal vWF and the disease is often fatal. More information about Type III vWD can be found at http://www.vetgen.com/sheltvwd.html.

In every breed for which the genetics has been defined, vWD is inherited as a simple (autosomal) recessive. This means that an affected dog has two copies of the defective gene, and that both of its parents are either carriers or are affected. Carriers have one normal gene and one affected, while unaffected (clear) dogs have two copies of the normal gene.

Historically, the only way to diagnose vWD was to test a blood sample for the presence of vWF. Recently the DNA mutations which cause vWD in several breeds have been identified and accurate tests for the presence of the abnormal gene exist for use in those breeds. For breeds where no DNA test exists, the vWF test is still used.

Von Willebrand’s factor testing is usually done by comparing a pool of normal dogs von Willebrand’s factor levels with the patient’s levels and the result is given as a percentage.  Blood from a number of apparently normal dogs is tested for the amount of (vWF) and their average level is considered to be the “100%” level. Then the lab assigns a range that is considered a normal result.

Historically, vWF test results were interpreted in a manner similar to this:

Normal Range 70 – 180%
Borderline Range 50 – 69%
Abnormal Range 0 – 49%

Dogs testing in the normal range were generally considered clear of vWD, and at low risk for expressing or transmitting the vWD gene.

Dogs testing in the borderline range could not be accurately classified as affected, carrier or clear of vWD on the basis of that measurement. This is an overlap region where some individuals are clear, some are carriers and some are affected with vWD.

Dogs testing in the abnormal range were generally considered affected with vWD and at risk for transmitting an abnormal vWF gene to their offspring, and in some individuals for expressing an abnormal bleeding tendency.

Now that clear, carrier and affected status can be accurately determined by DNA testing in some breeds, comparisons of the results of the vWF test to the results of the DNA test can be conducted. As published on the VetGen web site http://www.vetgen.com/correlat.html, DNA testing reveals that unless the vWF levels are extremely low, or extremely high, that vWF levels do not accurately indicate affected, carrier or clear status.

In addition, published works reveal that in any given dog, vWF results can vary from hour to hour and day to day and that factors such as stress, estrus or other illness may impact the results.

So… what does this mean? If vWF testing isn’t 100% accurate, why do it? In short, because, at present, its all we have. Levels less than 20 or 25% indicate very little normal vWF is being produced and that the dog is probably affected and at risk for bleeding. Very high values, those greater than 100% probably indicate that the dog is free of the disease. Dogs testing in any other range should be evaluated in light of the whole picture. What is the status of the dogs parents and littermates? Has the dog ever exhibited any bleeding tendencies? What are the results of repeated vWF level tests? All of these questions may provide insight to an individual dogs status.

As IG breeders begin testing more regularly for vWD, its likely that many affected and carrier dogs will be detected. In Doberman Pinschers, the gene is widespread. Only about 20% of the dogs are clear (unaffected). About 50% are carriers and another 30% are affected.

If the incidence in IGs is similar, we clearly can’t afford to cull every affected or carrier dog from our breeding programs. On the other hand, we can’t afford to ignore this problem. Until a DNA test becomes available, it’s important to remember that vWF testing is not as accurate as using a DNA test to determine clear, carrier or affected status.

Dogs testing less than 25% are generally accepted as affected and in the absence of a DNA test, probably should not be bred. Owners should inform any veterinarians treating the dog that it is affected with vWF, particularly if any surgery is contemplated. Prior to surgery, the production of vWF can be stimulated by administration of a substance known as DDAVP and if excessive bleeding occurs, administration of blood clotting factors may be necessary.

Dogs that test in the range of 80% and higher can probably be considered clear, at least until a DNA test becomes available.

So, what do you do if your dog tests in the range that indicates that it is a carrier? First, don’t panic. Remember that this dog might be prone to prolonged bleeding and be sure your veterinarian is aware of the dogs status. As for the breeding future of the dog, take a good hard look at the individual. Is this a dog with a lot to contribute to the breed? Is it otherwise healthy? What is the vWD status of the prospective mate? Considering the possibility that a DNA test might exist in the future could this breeding be postponed?

Reducing the incidence of the vWF gene is an important goal for IG breeders. However, like most purebred dogs, IGs have a relatively limited gene pool, and excessive culling can reduce genetic diversity. Make breeding decisions with the best interests of the breed in mind. No one ever said that breeding dogs responsibly would be easy.