Doberman in field

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, like hemophilia A, is 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. 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 the production of fibrin (the material scars are made of) to more permanently seal the vessel. Von Willebrand's factor acts as the 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.

See a short video depicting the normal blood clotting system.

When there is something wrong with a body's von Willebrand's factor, platelets do not stick together properly and inappropriate, prolonged wound bleeding occurs.  Bleeding can be noted in association with minor injury or surgery but can also manifest as spontaneous bleeding, especially recurring nose bleeds, bloody urine, and/or black tarry diarrhea.

Types of Von Willebrand's Disease

There are three types of von Willebrand's disease.

Type I
In Type I von Willebrand's disease, 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.

Type II
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 German Wire-Haired Pointers.

Type III
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 it have been found in over 50 breeds, as well as in cats and humans. Unlike the genetics of Hemophilia A in humans, which is reviewed in detail in virtually every high school biology class as an example of a classic 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.

Testing for Von Willebrand's Factor

Knowing a dog's von Willebrand's status is important clinically when there is concern about a patient's ability to clot, and it’s also important before breeding.  With breeding, it is important to identify genetic carriers of von Willebrand's. A carrier of von Willebrand's should under no circumstances be bred to another carrier as this is likely to create affected dogs, so members of the classically affected breeds should be screened. There is great controversy as to whether carriers should even be bred at all, as this will potentially create more carriers.

Classically, testing for this 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 percent.

Normal is considered to be 70-180 percent.

Borderline is considered to be 50-69 percent.

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 the dog has and further testing by a technique called electrophoresis is needed to do this if you are interested. Knowing the type of von Willebrand's disease is unlikely to change therapy, thus, further testing is not commonly done.

DNA Testing

DNA testing is currently available for many von Willebrand's breeds. At present, there are many DNA testing labs throughout the U.S. and Europe that can test for von Willebrand's disease. Typically, the pet owner receives a test kit that can be used at home and instructions on how to collect a cheek swab from the dog's mouth.  Results should indicate if the patient is clear, affected, or if the patient is a carrier.

Testing Clotting Ability Prior to Planned Surgery

A simple screening test often done before surgery is a buccal bleeding time. A small wound is created in the mouth using a spring-loaded blade created just for this purpose (a Symplate device or Surgicutt device). The time required for clotting to occur is measured and should be under four minutes or so if platelet function is normal. 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 there are too many toenail variables to create a standardized test. That said, there are some issues with buccal bleeding time as well. Even though the spring load is standardized, as is the length and sharpness of the instrument, there is still some subjectivity in positioning the device, as well as some patient variables (red blood cell concentration, blood viscosity, etc.) that can influence results.

In a perfect world, a platelet function analyzer is used to measure what is called a collagen/ADP closure time. This is the most accurate measurement of how well platelets adhere and form clots, but this technology is not readily available to most small animal hospitals at this time.

Suddenly Symptoms?

You 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.

It is possible for borderline dogs to show signs of bleeding later on. For example, a dog with borderline von Willebrand's factor might become hypothyroid later in life, and this hormonal change could be just enough to make the bleeding disorder clinically evident. This is not a common scenario with hypothyroidism, but it has been reported. 

Treatment of the Affected Dog

When hemorrhage is occurring or is anticipated, as with a planned surgical procedure, the best treatment is the 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 activation period, the use of DDAVP shortens the bleeding time for approximately 2 hours after the DDAVP injection. This is very helpful in preparing for surgery but not something useful on a day-to-day basis.

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 have 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 it is a special concern for at-risk breeds. If you have questions, your veterinarian’s office will be happy to answer them.