Hemophilia B (F9 gene, Lhasa Apso)

Hemophilia B or factor IX deficiency is a genetic disease that affects the ability of the blood to clot properly when there is an injury or surgical intervention. In dogs, this condition is less common than hemophilia A.

Symptoms

Dogs affected by hemophilia may suffer spontaneous hemorrhages that are usually quite prolonged. Prolonged hemorrhages may also occur after surgery or muscle or joint injury. Muscle and joint hemorrhages can result in swelling and lameness, while acute blood loss can result in hypovolemic shock. Since the F9 gene is located on the X sex chromosome, females carrying one copy of an F9 mutation usually show no symptoms, while males do show signs. The severity depends on the levels of residual clotting activity. Affected animals have very low circulating levels of factor IX and carrier females have levels reduced to about half of normal (40-60%).

Disease Management

Treatment of hemophilia B focuses on controlling symptoms and preventing severe bleeding. Repeated transfusions of whole blood or plasma are required until the bleeding is controlled. If you suspect your dog may have hemophilia B, it is crucial to take him to a veterinarian for proper diagnosis and treatment.

Genetic basis

This disease follows an X-linked recessive mode of inheritance. Recessive X-linked inheritance means that female dogs must receive two copies of the mutation or pathogenic variant (one from each parent) to develop the disease, whereas males need only one copy of the mutated gene or variant from the dam to develop the disease. Male dogs usually show symptoms of the disease. Each male puppy born to a mother carrying the mutation has a 50% chance of inheriting the mutation and thus the risk of developing the disease. Bitches that do not carry the mutation are not at increased risk of having affected puppies. Breeding between dogs carrying genetic variants that can cause disease, even if they do not show symptoms, is not recommended.

Technical report

The clotting process involves many different proteins, and deficiency of any of these proteins can cause bleeding disorders, such as deficiencies of factor II (prothrombin), factor VII, factor VIII, and factor IX. Vitamin K deficiency, which is also part of the clotting process, can worsen a clotting defect. Like hemophilia A, hemophilia B is an X-linked recessive disease that has been described in at least 26 breeds of dogs. Factor IX deficiency in Lhasa Apso breed dogs is caused by a complex mutation, called c.548_553delinsT, which results in a premature stop codon. resulting in no functional factor IX being produced.

Most affected breeds

Airedale Terrier
Cairn Terrier
German Wirehaired Pointer
Hovawart
Labrador Retriever
Lhasa Apso
Newfoundland
Rhodesian Ridgeback

Bibliography

Dodds WJ. One Health: Animal Models of Heritable Human Bleeding Diseases. Animals (Basel). 2022 Dec 26;13(1):87.

Mauser AE, Whitlark J, Whitney KM, Lothrop CD Jr. A deletion mutation causes hemophilia B in Lhasa Apso dogs. Blood. 1996 Nov 1;88(9):3451-5.