Many times, if you are familiar with a condition in humans, you are also largely familiar with it in dogs.
Hemophilia in dogs falls into this category.
Hemophilia is a blood disorder with a genetic and hereditary basis that causes issues with blood clotting.
There are two main types, both with X-linked recessive inheritance:
- Hemophilia A in dogs: A mutation in the F8 gene that causes a deficiency in coagulation factor VIII.
- Hemophilia B in dogs (Christmas disease): A mutation in the F9 gene, which causes a deficiency in coagulation factor IX.
The difference between hemophilia A and B in dogs lies in the affected gene.
Since these disorders are linked to the X chromosome, the mutated gene is often transmitted by the mother, who is asymptomatic. There would be a 50% chance that male offspring would develop the disease, while female offspring would be carriers instead.
They are usually inherited, but there have been cases of the disease arising due to a spontaneous mutation in the affected individual.
These are the two most common genetic disorders associated with severe bleeding after Von Willebrand disease.
Yes, although it’s a common mistake, Von Willebrand disease is not classified as hemophilia.
Unlike hemophilia, it is not transmitted via the X chromosome; it is autosomal recessive, so the risk is the same for males and females. Hemophilia is more common in males than in females.
Additionally, Von Willebrand disease is a milder condition. It does not affect the coagulation cascade but rather the ability of platelets to adhere and aggregate to form plugs during bleeding.
One way to distinguish between them is by considering the difference in severity. If symptoms include pain or stiffness in muscles and joints, it could be due to internal bleeding, which is common in hemophilia but not in Von Willebrand disease.
The altered gene is the VWF gene, and animals can go their entire lives without showing symptoms or experiencing complications. We will talk about this in more detail another day.
Managing hemophilia in dogs is challenging. There is no cure yet, although gene therapy projects are currently in development.
The only established treatment is the transfusion of fresh frozen plasma or cryoprecipitate to provide the coagulation factor that the dog naturally lacks.
Cryoprecipitate does not contain factor IX, so this method would only work for hemophilia A. Similarly, serum is a less effective treatment for hemophilia A than for hemophilia B.
That’s why it’s important to distinguish between the two.
Laboratory synthesis of coagulation factors has also been tested. In the case of hemophilia A, short-term results have been satisfactory.
Recovery and the severity of the condition vary among affected dogs. The deficiency of coagulation factors depends on the type of mutation they have.
Of course, breeding dogs that have or are carriers of the mutated genes for any type of hemophilia is a terrible idea and should always be avoided.
The coagulation cascade and hemophilia symptoms in dogs
The coagulation cascade begins with two different pathways, the intrinsic and extrinsic, which converge into a common pathway. It’s literal, that’s what it’s called.
The extrinsic pathway is named as such because coagulation begins due to factor III, or tissue factor, which is found in certain cell types. Under normal conditions, it is hidden.
However, when there is an injury and rupture of blood vessels, the tissue factor (mainly from fibroblasts) comes into contact with the blood and coagulation begins.
The intrinsic pathway is slower but is necessary for the amplification and regulation of coagulation. It’s called that because, unlike the previous one, all the components involved are present in the blood from the start.
Factors VIII and IX, responsible for hemophilia A and B respectively, are part of the intrinsic pathway. Factor IX requires factor VIII as a cofactor during the cascade to reach the final common pathway.
For this reason, if a coagulation test were done following the extrinsic and final pathway, a hemophilia patient would have normal times. Patients are able to coagulate blood, but less efficiently than a healthy individual.
A case is considered very severe when the amount and/or activity of either factor is below 1% compared to a healthy individual.
The symptoms of hemophilia in dogs include excessive bleeding, bruising, joint pain, nosebleeds, anemia, and weakness.
Hemophilia A, factor VIII
This is the most common type of hemophilia in dogs, and it can occur in all breeds. However, it is especially common in the German Shepherd (caused by two independent mutations), followed by other breeds such as the Doberman Pinscher and the Labrador Retriever.
The disease tends to be more severe in large breeds than in small ones.
The definitive diagnosis is made by measuring the coagulating ability of factor VIII, to rule out other problems in the cascade.
The F8 gene is very similar between humans and dogs, and the resulting protein has key functional regions that are identical in both species. This allows research in either species to be greatly beneficial for the other.
One of the common mutations is the inversion in intron 22. This same mutation has been found in almost half (approximately 40%) of humans with severe hemophilia A.
Hemophilia B, factor IX
Less common than hemophilia A, there are approximately 25 dog breeds where this condition has been reported.
Perhaps the breed most studied for this condition, and therefore most associated with it, is the Lhasa Apso.
Just like hemophilia A, large breeds have a harder time.
The protein resulting from the F9 gene has an 86% similarity to the human version when comparing amino acid sequences.
There are genetic variants of the disease that are specific to certain breeds. That is, the mutation responsible has only been detected in that breed. This happens in both types of hemophilia and is important to keep in mind.
A test designed to detect hemophilia in a Miniature Schnauzer often will not recognize the condition in an Irish Setter, because the same disease caused by a different mutation would not be detected by those tests.
That’s why many genetic tests for diseases in dogs specify the breed or genetic variant they detect. One of them, and subjectively speaking the most reliable, is the Koko genetic test for dogs.