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.
Breeds routinely tested are Doberman Pinscher, Golden Retriever, Shetland Sheepdog, Rottweiler, Miniature Schnauzer, German Shepherd, German Short-Haired Pointer, Standard Poodle, and Scottish Terrier.
What is Von Willebrand’s Factor?
Von Willebrand’s factor is a protein complex 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 one 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 of, to more permanently seal the vessel. Von Willebrand’s factor acts as glue holding the platelets together and holds 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 only in very small 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, leaving only the smaller proteins to do the job. 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, 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 than 100%).
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%, although 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.
At the time of this writing, DNA testing is currently available for 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.
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.
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.
Borderline dogs often show signs of bleeding later on. For example, sometimes a dog with borderline von Willebrand’s factor will show a slight drop in platelet function 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 by transfusion. Pure von Willebrand’s factor cannot be purchased from a blood bank but a blood product called cryoprecipitate, which is particularly rich in von Willebrand’s factor, can be. 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. After a 30 minute onset period, the use of DDAVP shortens the bleeding time for approximately 2 hours after the after DDAVP injection.
There are two considerations with von Willebrand’s disease: screening breeding animals so that this genetic disorder is not passed on, and identifying and treating affected animals. If you own a member of one of the “at risk” breeds, consider having a screening test, especially if you are considering a major surgery. If you plan to breed your pet, von Willebrand’s testing is a good idea regardless of the breed but is a special concern for the “at risk” breeds. If you have questions, your veterinarian’s office will be happy to answer them or use the Ask A Vet feature on Veterinary Partner’s home page.