Nancy McDonald, BSN, RN
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.
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.
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, (www.bichonhealth.org/HealthInfo/Hemolytic.htm) 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.
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 (www.bichonhealth.org/HealthInfo/Thrombocytopenia.htm) 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.
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.