Hemophilia A

Severely affected puppies bleed from a few weeks of age; littermates have died or been euthanised by seven weeks. Typical signs of a secondary haemostatic defect are large haematomas and bleeding into joints and body cavities rather than petechiae. Reported episodes include spontaneous haematomas of the limbs, head, neck and shoulder, lameness from haemarthrosis, suspected haemothorax with cough and laboured breathing, oral bleeding when teeth are shed, nosebleeds, gum bleeding, melaena and prolonged bleeding after castration, suturing or microchipping, often with blood loss anaemia. Research-colony dogs average about four to six spontaneous bleeds a year. Laboratory findings are a prolonged aPTT with a normal prothrombin time.

Haemophilia A is an inherited deficiency of coagulation factor VIII, a disorder of secondary haemostasis. Activated factor VIII is the cofactor that greatly accelerates the activation of factor X by activated factor IX in the intrinsic pathway. Without it, too little factor Xa, and therefore thrombin, is generated, so fibrinogen is not converted into a stable fibrin clot. In dogs, as in people, severe disease corresponds to factor VIII activity below 1% of normal, and clinical severity is inversely related to the circulating factor VIII level. Causal mutations in dogs include a factor VIII gene inversion (intron 22) in the Chapel Hill research colony and a nonsense point mutation creating a premature stop codon in an Old English Sheepdog.

The factor VIII gene is on the X chromosome, so males are affected and females are usually carriers; an affected male dog sired a litter with five carrier daughters. Haemophilia A and von Willebrand disease are the most common inherited bleeding disorders in dogs. Reported breeds include Irish Setters (founders of a colony kept since 1947), a German Shepherd cross, a Staffordshire Bull Terrier and an Old English Sheepdog; cases can appear without any family history of bleeding. Inherited haemostatic disorders are recognised most often in dogs, are rare in horses and cattle, and occur in cats, which often show no bleeding until surgery such as neutering.

Haemophilia B (factor IX deficiency) is clinically indistinguishable and is separated by factor VIII and IX activity assays. Von Willebrand disease is a primary haemostatic defect with mucosal bleeding and low von Willebrand factor; in haemophilia A von Willebrand factor is normal or high. Anticoagulant rodenticide poisoning should be considered, but haemophilic bleeding does not respond to vitamin K and the prothrombin time is normal. Acquired disorders such as immune-mediated thrombocytopenia, liver disease and disseminated intravascular coagulation are more common in practice, especially in older animals.

Blood coagulation system (intrinsic pathway, factor VIII), joints, subcutaneous and muscle tissue, oral cavity and gums, nasal cavity, thoracic cavity, gastrointestinal tract

Inherited and X-linked: affected males sire carrier daughters. Where a family's factor VIII mutation is known, PCR genotyping can identify affected and carrier offspring.

Untreated, bleeding in severe cases is debilitating and can be fatal. Plasma, cryoprecipitate or canine factor VIII controls episodes, but treatment is lifelong and costly; prophylaxis or gene transfer reduces bleeding frequency without full correction.