Factor VIII deficiency
Factor VIII is a trace plasma glycoprotein involved as a cofactor in the activation of factor X by factor IXa.
A deficiency in factor VIII is caused by a series of multiple genetic transcript mutations in factor VIII synthesis (the FVIII gene (F8) contains 26 exons and spans 186 kb of DNA). This results in reduced levels and activity of factor VIII, leading to abnormal primary thrombocyte plug formations and progressive perivascular bleeding, particularly around highly mobility areas such as joints.
This disease primarily affects male dogs (females are usually heterozygous carriers) and has been reported in the Golden Retriever, Havanese, Weimaraner, German Shepherd, German Short-haired Pointer, Chow Chow, Keeshonden and Irish Setter.
The clinical severity of this condition in dogs is inversely proportional to the circulating factor VIII level in plasma, and severe disease is associated with levels of factor VIII <1% of normal.
Clinical symptoms usually involve a predisposition to developing spontaneous hematomas anywhere on the body surface as well as hemoabdomen, hemothorax and hemarthrosis around joints, resulting in lameness and in rare cases, acute paraplegia due to intraspinal hemorrhage.
Problems often arise after vaccination, as live vaccines effect the number and function of clotting cells for a period of 10 - 14 days after vaccination. There may be excessive bleeding during teething and puppies may suffer from bloody diarrhoea. Dogs with mild deficiencies may only display hemorrhage associated with trauma or surgery.
Diagnosis is usually based on coagulation screening tests for detection of factor VIII levels. Factor VIII-coagulant (FVIII:C) activity < 0.7 IU m/L is consistent with a diagnosis of hemophilia A, although the sensitivity of this assay is only moderate.
Identification of carriers should be done with caution in animals < 6 months of age (as young animals have lower FVIII:C activities than adults). Carriers usually have a normal APTT and ACT.
Treatment of acutely affected dogs requires repeated intravenous injections of fresh frozen cryoprecipitate plasma until bleeding is controlled (usually given at 2 ml/kg).
The experimental use of solulin, a soluble form of thrombomodulin which increases clot lysis time, may be advisable.
Desmopressin has been shown to significantly increased factor VIII levels when administered subcutaneously into dogs but in factor VIII deficient dogs, does not correlate with significant increases in serum factor VIII levels.
Exercise appears to play an important role in improving hemostasis in dogs affected by this condition, although excessive exercise should not be entertained.
Recombinant factor VIII is available as an alternative treatment but is expensive, inconvenient, and complicated by development of antibodies that inhibit FVIII activity within 1 - 2 weeks of therapy.
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