Hemophilia A (F8 gene, Old English Sheepdog)

Hemophilia A is the most common inherited bleeding disorder in dogs. When a mutation occurs in the F8 gene, which produces clotting factor VIII, the blood clotting process is altered increasing the risk of uncontrolled bleeding.

Symptoms

Since the F8 gene is located on the X sex chromosome, females carrying one copy of an F8 mutation usually show no symptoms, whereas males do show signs. The severity depends on the levels of residual clotting activity. When factor VIII activity is less than 5%, symptoms usually appear after birth and are more severe. There is spontaneous bleeding into joints and leakage of blood into the body cavity which can be lethal. Prolonged bleeding from the umbilical cord, gums during teething and after surgery is also observed. Dogs with factor VIII activity of 5% to 10% usually do not bleed spontaneously, but bleed more than normal after injury or surgery.

Disease Management

Treatment of hemophilia A focuses on controlling symptoms and preventing severe bleeding. Treatment requires repeated transfusions of whole blood or plasma until the bleeding has been controlled. If you suspect your dog may have hemophilia A, it is important 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. Deficiency of vitamin K, which is also part of the clotting process, can worsen a clotting defect. In an English shepherd dog that had suffered multiple bleeding episodes in the first few months of life, Lozier et al. identified a mutation in the F8 gene encoding coagulation factor VIII, which causes severe hemophilia A. This mutation, called c.177, is called the clotting factor VIII mutation. This mutation, called c.1786C>T, produces a premature stop codon in the protein.

Most affected breeds

Boxer
Cocker Spaniel
German Shepherd Dog
German Shorthaired Pointer
Golden Retriever
Irish Setter
Malinois
Miniature Schnauzer
Old English Sheepdog
Poodle
Rhodesian Ridgeback
Siberian Husky
Weimaraner

Bibliography

Lozier JN, Kloos MT, Merricks EP,et al. Severe Hemophilia A in a Male Old English Sheep Dog with a C→T Transition that Created a Premature Stop Codon in Factor VIII. Comp Med. 2016;66(5):405-411.