Bioguard Corporation
Canine Factor VII (FVII) deficiency is an autosomal recessive genetic disorder that leads to a mild to moderate blood clotting problem in affected dogs. Puppies with the condition may exhibit symptoms such as nosebleeds (epistaxis) and gum bleeding, while adult dogs are more prone to bruising and skin issues like dermatitis. Though bleeding episodes tend to decrease in severity as the dog matures, the disorder still causes ongoing issues throughout the animal’s life. FVII deficiency was first identified in the Migluo breed. Most dogs are diagnosed when they visit a veterinarian due to accidental injury, spontaneous bleeding, genetic screening, or blood tests.
Pathogenesis
Hemostasis is achieved through a series of events known as the coagulation cascade, which involves two interconnected pathways: the intrinsic and extrinsic pathways. The intrinsic pathway is triggered by spontaneous internal damage to the blood vessel lining, while the extrinsic pathway is activated in response to external trauma.
Factor VII (FVII) is a vitamin K-dependent glycoprotein produced in the liver and released into the bloodstream as a single-chain zymogen. Once activated, FVII plays a crucial role in initiating coagulation. Following vascular injury, FVII, along with tissue factor (TF) and calcium, activates factors IX and X, leading to thrombin production. A deficiency in FVII impairs blood clotting, resulting in excessive bleeding during injuries or surgeries.
Diagnosis
- The Buccal Mucosal Bleeding Time (BMBT) is the most commonly used test for measuring bleeding time in small animals. To perform the BMBT, the upper lip is folded back and secured with a gauze strip around the maxilla or both the maxilla and mandible. A small incision is made in the mucosa above the premolars, avoiding areas with visibly engorged vessels. Blood from the incision is gently blotted using filter paper placed near the incision without touching it. A stopwatch starts when the incision is made and stops when no blood crescent forms on the filter paper. To reduce variability, the same person should perform the BMBT whenever possible.
- Activated Partial Thromboplastin Time (APTT) measures the overall speed of blood clot formation through the intrinsic and common coagulation pathways. It assesses the activity of factors XII, XI, IX, VIII, X, V, II, I, as well as prekallikrein (PK) and high molecular weight kininogen (HK).
- Prothrombin Time (PT) is used to evaluate the extrinsic and common pathways of coagulation by measuring factors VII, X, V, II, and I.
- Factor VII deficiency is suspected when a dog presents with a prolonged PT and normal BMBT and APTT. Genetic testing can also identify affected dogs or carriers, especially in certain breeds.
Breeds at Risk
Canine Factor VII deficiency has been documented in several breeds, including the Beagle, Airedale, Alaskan Klee Kai, American Foxhound, Finnish Hound, German Wirehaired Pointer, Giant Schnauzer, Irish Water Spaniel, Japanese Spitz, Miniature Schnauzer, Papillon/Phalene, Sealyham Terrier, Scottish Deerhound, and Welsh Springer Spaniel.
Management
There is currently no cure for Factor VII deficiency. However, clinical symptoms can be managed through transfusions with fresh plasma or blood, or by administering recombinant activated human FVII. These treatments provide only temporary relief. Fortunately, dogs with mild to moderate FVII deficiency typically lead normal lives.
References
Callan MB, Aljamali MN, Margaritis P, Griot-Wenk ME, Pollak ES, Werner P, Giger U, High KA. A novel missense mutation responsible for factor VII deficiency in research Beagle colonies. J Thromb Haemost. 2006 Dec; 4(12):2616-22.
Carlstrom LP, Jens JK, Dobyns ME, Passage M, Dickson PI, Ellinwood NM. Inadvertent propagation of factor VII deficiency in a canine mucopolysaccharidosis type I research breeding colony. Comp Med. 2009 Aug;59(4):378-82.
Donner J, Kaukonen M, Anderson H, Moller F, Kyostila K, Sankari S, Hytonen M, Giger U, Lohi H. Genetic Panel Screening of Nearly 100 Mutations Reveals New Insights into the Breed Distribution of Risk Variants for Canine Hereditary Disorders. PLoS One. 2016 Aug 15;11(8):e0161005.
Kaae JA, Callan MB, Brooks MB. Hereditary factor VII deficiency in the Alaskan Klee Kai dog. J Vet Intern Med. 2007 Sep-Oct;21(5):976-81.
