Hemophilia

Liaison: Jan Young

Hemophilia is a disease of the clotting system of the blood and is the most common bleeding disorder in cats and dogs. The clotting mechanism is a cascade of events, each event dependent on a different protein factor. There are two primary types of hemophilia: hemophilia A and hemophilia B. Hemophilia A is a deficiency of factor VIII; hemophilia B is a deficiency of factor IX. Hemophilia A is more common and its severity is dependent on the level of factor VIII activity. Hemophilia B is more rare but is often more severe.

Hemophilia is transmitted by X-linked inheritance, a type of inheritance where the abnormal gene is carried on the X chromosome. This means it is transmitted by mothers to sons through the X chromosome. Thus the disease shows up mostly in males because they have only one X chromosome. Since females have two X chromosomes (and only one is typically affected) they show fewer signs of the disease but are carriers and may pass the disease on to their sons. It is more common in some breeds than others, and the Samoyed is listed on several websites as one of these breeds. However, the original source of this information is unclear, and the disease has not been described in Samoyeds in the scientific literature. It is a relatively rare disease in Samoyeds.

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There are more than a dozen proteins involved in the clotting mechanism. Hemophilia A and B are only two of the bleeding disorders that may be seen in dogs, there are at least five others that have been reported in one or more breeds, including a deficiency of von Willebrand Factor. The other bleeding disorders are also inherited, but not X-linked. They have not been reported in Samoyeds.

This paper is a good review of canine bleeding disorders:

Brooks M. 1999. A review of canine inherited bleeding disorders: Biochemical and Molecular Strategies for Disease Characterization and Carrier Detection. Journal of Heredity 90: 112-118. 2 bones

Figure 1 in this paper has a diagram of the canine clotting mechanism cascade showing all of the factors involved:

Nichols TC et al 2009. Protein Replacement Therapy and Gene Transfer in Canine Models of Hemophilia A, Hemophilia B, von Willebrand Disease, and Factor Vii Deficiency. ILAR Journal 50: 144-167. 3 bones

Signs and Symptoms

Depending on the severity of the disease, signs range from few, if any, to severe problems with bleeding. In mild cases there may only be problems with surgery or with trauma. In more severe cases there can be spontaneous bleeding under the skin, into joints or internally.

First signs may be prolonged bleeding with loss of baby teeth, swelling and lameness of a joint following very mild trauma, bloody diarrhea, and hematomas (lumps under the skin caused by local bleeding) often following vaccinations. Prolonged and/or recurrent bleeding into joints and muscles is common in more severe cases and can result in permanent lameness and deformity. In very severe cases the dog may bleed to death at a very young age.

Causes

As noted above, hemophilia A and B are X-linked inherited defects.

Risk Factors

Related family members with the disease.

Diagnostic Tests

If a dog appears to have a bleeding disorder based on an exam and history, the first step is typically a panel of special bleeding tests (coagulation panel) to evaluate the blood’s ability to clot in a test tube. Results of these tests can help determine which of the many factors in the clotting cascade might be low/missing.

Once the coagulation profile is determined, specific assays are available for the levels of factor VIII, factor IX, and some other factors. These tests can confirm that a dog has a specific bleeding disorder, but it cannot rule out a carrier state because carriers may have normal levels.

Genetic (DNA) tests for the carrier state of Hemophilia B, factor VII deficiency and von Willebrand’s disease (another clotting disorder) are available from Embark for certain breeds, but not for Samoyeds.

Embark

Treatment Guidelines

Note: Treatment of animals should only be performed by a licensed veterinarian. Veterinarians should consult the current literature and current pharmacological formularies before initiating any treatment protocol.

Mild cases may require no treatment.

More severe cases may require periodic blood or plasma transfusions. These may need to be repeated frequently during episodes of bleeding until the bleeding has stopped. A problem with transfusions is they may become ineffective because of the development of antibodies against the factor, rendering it ineffective.

Gene transfer (gene therapy) is a process where a normal gene for a factor is inserted into an animal’s cells so that the animal can make the missing factor. Research has been ongoing for many years, mostly with disappointment. In recent years, however, it has been more promising. Although there have been canine cures described, I was unable to find any evidence that it is being used in canines for anything other than research purposes. It could have the same problem with development of antibodies as plasma transfusions. I suspect that this treatment is prohibitively expensive.