Canine von Willebrand's Disease is an inherited deficiency in one of the clotting factors of the blood. It is similar to haemophilia in some respects, but may appear in either male or female. "Carriers" may show no overt symptoms of the disease, but their progeny can have severe bleeding problems. Dogs affected with vWD may have symptoms varying from very mild to severe or lethal. These bleeding problems include prolonged bleeding from toenails cut too short, hemorrhage from even minor surgical procedures, lameness, hematomas, stillbirths or early death of newborn puppies, intestinal bleeding, and so on. The bleeding primarily involves mucosal surfaces (gastrointestinal tract, nose- bleeds, blood in the urine, vaginal or penile bleeding) and is aggravated by stress situations (other physiological, pathological, emotional or hormonal conditions).

Selected recent references:-

Meyers, K., Wardrop, K.J., and Meinkoth, J., " Canine vWD: Pathobiology, diagnosis, and short-term treatment", Compendium on Continuing Education for the Practicing Veterinarian, 1992, Vol 14(1), pp.13-23

Stokol, T. & Parry, B.W., "Canine von Willebrand Disease: a review", Australian Vet. Practitioner,1992, Vol 23 (2), pp. 94 - 103 

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The mutation itself has some interesting aspects. For one thing, precisely the same mutation has occurred in some human patients with vWD. It is a little unusual to see mutations be identical across species. This shows how closely we are related to our canine brethren! Second, the mutation is of a type such that completely normal von Willebrand's factor (vWF) is made about 5-10% of the time. Technically, the mutation is called a splice site mutation, with alternative splicing occurring about 90-95% of the time. That jargon won't mean much to the average breeder or owner, but let me explain what is happening in layperson language. It may be useful to understand the mutation to a certain extent, because its nature explains why it was so confusing to understand for a long time, and it also explains why affected Dobermans have a milder disease than, say, affected Scotties.

To try to understand the effects of this mutation, let's use an analogy common to general experience. Imagine that a freight train is supposed to go from point A to point B following a railroad track. There is a point where a sidetrack goes to point C. However, normally the train never goes to point C, because the switch to point C, connecting the track up to the main track, is never thrown. Then the switch breaks (this is the mutation) such that the lock holding the switch from connecting the track to point C is no longer effective. The switch can now jiggle back and forth, sending some trains to point B, and others to point C. As freight trains rumble towards the switch, 95% of the time it jiggles over and causes the train to end up at point C. This is useless because point C ends at a cliff. The trains rumble over the cliff and are never heard from again. A minority of the time, maybe about 5%, the switch jiggles the other way and the trains end up at their normal destination. So, only 5% of the freight is delivered.

This is exactly what happens in the Doberman affected animal. These animals have two doses (two trains in the above example) of the mutated gene. Each gene is capable of making 5-10% of normal vWF (that is, going down the main track to point B), because the normal splice site is used a little. The 90-95% of the time the mutated splice site is used (going down the side track to point C), no useful vWF is produced. Since each of the two mutated genes is producing 5-10% of normal vWF the affected Doberman ends up with twice that, or 10-20% of normal vWF in their blood.

So, one of the mysteries of Doberman vWD that has puzzled scientists for years, how affected dogs can end up with a small amount of completely normal vWF, is cleared up by understanding this type of mutation. A second mystery is also cleared up. Doberman owners and breeders have had their dogs tested for vWF for years using the protein assay of vWF, and have often discovered low values in dogs without a bleeding history, even at surgery. The reason is, such dogs have 10-20% of normal vWF. If the bleeding stress isn't too great, the 10-20% of normal vWF that is present can prevent undue bleeding. Part of the time uneventful surgery fits that criterion, and unusual bleeding does not occur.

I hasten to add that this should not be taken to mean that vWD in the Doberman is clinically harmless. The literature is full of reports of Doberman's bleeding and dying from vWD. There are a number of factors, known and unknown, which will affect the clinical outcome in a given case. First coagulation factors, such as vWF, are consumed during blood clotting. The more the bleeding, from injury or surgery, the more the consumption, and the more likely the limited supply of vWF in an affected Doberman will be used up, leading to renewed bleeding, now from vWF deficiency. Second there is also variation in the amount of vWF in affected Dobermans. A dog with a 5% value is at greater risk than one with 15%. Of course, other factors, such as other coagulation and tissue factors that we aren't measuring, will certainly vary from one affected dog to another, and change the risk of bleeding up or down in a given situation.

Another mystery about Doberman vWD that we now understand better is the actual frequency of vWD in Dobermans. Dobermans have been said to have a 70% plus frequency of this disease, but that is not correct. It's more on the order of 35% affected, with an additional large group being carriers, but free of any bleeding risk. The disease is an "autosomal recessive", which means that affected animals have two doses of the mutated gene, and a mild to moderate risk of bleeding, for reasons explained earlier. Based on very preliminary data, we believe the mutant gene has a frequency of about 0.6 (60% of the genes are mutant) which translates into about 36% of all Dobermans being homozygous affected (two doses of the abnormal gene and at risk for bleeding), 48% being carriers (one abnormal and one normal gene, no risk of bleeding), and 16% being homozygous clear (two doses of the normal gene). If the gene frequency turns out to be closer to 0.5, the frequencies for affected will be 25%, carriers 50%, and clear 25%. Of course, our small sample comes from a limited region of the country. The gene frequencies may vary some in different parts of the country, but the bottom line will remain the same. This is a very common disease and a very common mutant gene.

Carriers of the mutant vWD gene are at no risk of bleeding from vWD, but of course, will transmit the mutant gene to their offspring 50% of the time. Roughly, the ranges of vWF factor levels are 5 to 20% for affected, 30-100% for carriers, and 50-130% for homozygous normal. Note the major overlap between carriers and normals for vWF levels. This overlap accounts for the extreme unreliability of the vWF assay in trying to identify Doberman carriers of vWD.