Genetic basis - Caused by mutations in the F8 gene located on the X chromosome, which encodes coagulation Factor VIII critical for blood clotting. Two specific missense mutations identified in German Shepherds: c.98G>A mutation (also called HEMA-1) causing a nonsense mutation (Trp33Stop). c.1643G>A mutation (HEMA-2) causing amino acid substitution (C548Y) in the A2 domain of Factor VIII. The condition follows an X-linked recessive inheritance, primarily affecting males with one X chromosome carrying the mutation. Females are carriers if heterozygous.
Pathophysiology - Mutation results in lack or severely reduced activity of Factor VIII, impairing the coagulation cascade. This leads to inability to form stable blood clots, causing excessive bleeding with trauma or spontaneous hemorrhages.
Complications - Clinical signs include prolonged bleeding, spontaneous hematomas, joint hemorrhages (hemarthrosis), nosebleeds, and bruising. Severe bleeding can cause life-threatening complications. Affected dogs may show signs early in life or after surgery/injury.
Why This Matters to Breeders and Vets - Prevents production of puppies with a severe bleeding disorder, improving breed health and welfare. Aids veterinarians in early diagnosis, treatment, and owner counseling. Understanding X-linked inheritance is crucial for breeding decisions. Helps maintain healthy German Shepherd populations by managing genetic risks.