von Willebrand’s Disease by Antonia Baker
Dobermanns, like many other breeds of dogs are affected by von Willebrand’s disease. This is an inherited bleeding problem that may result in delayed or failed clotting of the blood resulting in ongoing haemorrhage during surgery or if an injury occurs. Potentially, this disease can be fatal in dogs affected by it.
How blood clots (forms a scab) is quite complex. In simple terms, it requires some of the cells in the blood stream as well as a variety of special proteins also found in the blood itself as well as in lining of the blood vessels. When all of these substances interact under the right circumstances blood clots and forms a plug to stop the bleeding.
von Willebrand’s disease is the result of one of these special proteins being present in reduced amounts in the blood. This special protein in called von Willebrand’s factor and is vital in stabilising one of the proteins that causes blood to clot (Factor 8). The severity of the disease is proportional to the lack of von Willebrand’s factor in the blood.
In most cases it is thought that von Willebrand’s is transmitted in an autosomal dominant manner (more on this later). Dogs affected by this disease are more likely to have bleeding from the gums and inside the mouth mainly because blood vessels are close to the skin surface and minor trauma occurs when bones etc are chewed. Dogs may also have excessive bleeding from wounds, either if they have been in a fight or having undergone surgery. Finally, bitches may have excessive bleeding when they in heat and are at greater risk miscarriages if pregnant.
There are many different subtypes of the disease with the most common being type I. All the different subtypes are of little relevance. The thing to remember is that the disease is inherited (and technically should be able to be avoided in matings) and that it can cause significant problems in some dogs.
All species have two types of chromosomes: autosomal and sex chromosomes. To make things very simple lets assume that the sex chromosomes only determine the sex of a dog and the autosomal ones determine everything else i.e. coat colour, height etc.
As discussed in the Genetic Diseases article, every pup (or human) has 2 copies of the same chromosomes – one set from each parent. Therefore, if one of the parent’s has von Willebrand’s disease it will pass it on to the puppies.
If something is inherited in dominant manner than a pup only needs 1 copy of the bad gene to have the disease. The way the think about this that the “dominant” defective gene causing the disease overpowers or “dominates” the normal gene which would normally prevent the disease in the dog. If a disease is inherited in a “recessive” manner, the pup would need 2 bad copies of the gene (one from each parent) to have the disease. If it only got the bad gene from one parent it will be a “carrier” of the disease and could pass it on any pups it has but is not affected by the disease itself.
Diseases that are inherited in a purely dominant manner are easy to breed out because all dogs, regardless of them having 1 or 2 copies of the bad gene, will be affected with the disease which will be evident in their phenotype. That is, only dogs that have 2 normal copies of the gene will be phenotypic ally normal – thus if only these dogs are bred the bad gene will be eliminated from that line of dogs.
Unfortunately, in genetics things are never as simple as they seem. von Willebrand’s disease is inherited in an autosomal dominant manner but it has “incomplete penetrance”. This means that a dog that should genetically have the disease (i.e. genotype) may not actually be affected by it (i.e. phenotype). For this reason it was thought that the disease was actually inherited in a recessive manner rather than a dominant one.
So what is actually going on?
The way to think about von Willebrand’s disease is like having one lock and key ring with 20 identical keys on it. In a normal dog, that has 2 normal copies of the gene, the key ring would have 20 keys that all open the lock (and hence making von Willebrand’s factor every time the lock is opened). The opposite to that would be to say that a dog with 2 bad copies of the gene should have no keys on the key ring to open to lock and hence never make von Willebrand’s factor. However, what actually happens is that although the dog that has 2 diseased genes, there is a small amount of the gene that under some circumstances can make some of the factor. That is, think of a dog with 2 bad copies of the gene as having 1 out of 20 keys that can open the lock. A dog that has 1 good and 1 bad copy of the gene should theoretically be as badly affected as a dog that has 2 bad genes (as the bad gene completely dominates the good one). But, in von Willebrand’s disease a dog with one good and one bad copy of the gene can be thought of as having a key ring with 10 keys that open the lock and therefore producing reduced amounts of von Willebrand’s factor.
Blood tests that check the level of von Willebrand’s have been around for a while. But these are not accurate because it does not tell you anything about genotype. The problem is that different things, including stress, exercise and pregnancy can all cause an increase in von Willebrand’s factor. That is, a dog that normally has very low levels (i.e. 1 matching key) could have moderate levels (5-6 matching keys) under certain circumstances.
For this reason, the same dog can have 2 different test results, which is obviously not correct as their genes don’t change.
The only way to know exactly what your dog’s genotype is to perform a PCR test looking at the DNA (genes). This test will tell you if your dog has 2 normal genes, 2 disease causing mutations or one of each.
Many reasons. Firstly, for your dog’s health. Unfortunately, sometimes mans best friend is attacked by another dog or hit by a car. If you know that your dog has a bleeding problem you can tell the vet, as special drugs and blood products may need to be given. If your dog requires surgery, medication can be given beforehand to make the operation safer and reduced the risk of haemorrhage.
Secondly, if you are thinking of breeding you should get both parents tested so that you are informed about how the puppies are going to be affected. Potential puppy buyers are getting more informed about these sorts of matters. In the US there have been several cases of dog owner’s successfully suing breeders for selling them a dog with a genetic disease that could have been tested for.
Information is power – it allows us to make informed choices.
The genetic DNA test for von Willebrand's disease is a simple kit that involves taking a swab from the inside of the dog’s mouth. The swab is then sent to the US for DNA analysis.
References:
1. Pathological Basis of Disease 5th Ed, Robbins et al. (1995) p256 WB Saunders Publishing Co.
2. Control of Canine Genetic Diseases, GA Padgett, Howell Book House, pp41,46, 1998.
3.von Willebrand disease phenotype and von Willebrand factor marker genotype in Doberman Pinschers. Brookes MB et al (2001) American Journal of Veterinary Research 62(3):364-9.
4. Inheritance of von Willebrand factor deficiency in Doberman Pinschers. Moser J et al. (1996) Journal of American Veterinary Medical Association 209(6): 1103-6.
5.Plasma von Willebrand factor changes during various reproductive cycle stages in mixed-breed dogs with normal von Willebrand factor and in Doberman pinschers with type I von Willebrand’s disease. Moser J et al. (1998) American Journal of Veterinary Research 59(1):111-8.