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Factor VIII Deficiency or Haemophilia A in the Canine

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Haemophillia is a condition where the blood cannot clot properly after an injury.  It is one of the few sex-linked traits in dogs and is most common in males.  Unfortunately many dogs die before diagnosis.  Signs of thecondition include prolonged bleeding (particularly with the loss of baby teeth in puppies), bleeding under the skin and lameness, which is caused by bleeding into the muscle or joints.

Hemophilia A (Factor VIII: C Deficiency, Classic Hemophilia)

The most common of the severe inherited coagulopathies, hemophilia A occurs in humans, dogs, horses, sheep, cattle and cats. Mild, moderate, and severe forms of hemophilia have been recognized in humans and dogs, whereas the equine defect is usually severe and the feline defect tends to be mild. The canine disease has been reported in nearly every pure breed of dogs and in mongrels, but is most common in German shepherds worldwide having descended from the obligatory carrier progeny of an influential hemophilic stud. Smaller breeds tend to be less severely affected than larger breeds.

Hemophilia is an X chromosome-linked recessive trait in humans and other animals so usually females are asymptomatic carriers and males are affected.  Affected males are hemizygous for the trait, whereas carrier females are heterozygous and affected females (the product of a hemizygous and heterozygous mating) are homozygotes. This disease results in males from a very low concentration of clotting factor VIII:C, whereas carrier females have amounts of factor VIII:C of about 40-60% of normal.  Rarely, in highly inbred families, a carrier female mated with an affected male can produce affected female offspring. In affected puppies, prolonged bleeding is seen from the umbilical vessels after birth, from the gingiva during tooth eruption, and after surgery such as tail docking, dewclaw removal, or ear cropping. Hemarthrosis accompanied by intermittent lameness, spontaneous hematoma formation, and hemorrhagic body cavity effusions also are common clinical findings in dogs with <5% of normal Factor VIII activity. Animals with 5-10% of normal activity often do not bleed spontaneously but exhibit prolonged bleeding after trauma or surgery. Affected cats and, sometimes, small dogs may show prolonged bleeding after surgery or trauma but rarely bleed spontaneously, probably because of their agility and light weight. Affected animals usually have very low concentrations of Factor VIII (<10%) and prolonged ACT and APTT. Von Willebrand’s factor (Factor VIII-related antigen) concentrations are normal or greater than normal. Carrier animals have intermediate concentrations of Factor VIII (40-60%), and results of coagulation screening tests are usually normal.

Care should be taken in diagnosis if animals are <6 mo old because of possible low production of coagulation factors by an immature liver. Usually, results of coagulation screening tests are normal in carrier animals. Treatment of bleeding diatheses requires repeated transfusions of fresh whole blood, fresh plasma, or fresh-frozen plasma concentrates (6-10 mL/kg) 2-3 times/day until bleeding has been controlled. Plasma is preferable to whole blood because of the possible sensitization of the animal to RBC antigens.



ciddlogoa

Factor VIII deficiency or haemophilia A in the Canine

related terms:
 hemophilia A (factor VIII deficiency), hemophilia B (factor IX deficiency, Christmas disease)
http://www.upei.ca/cidd

What is hemophilia?
Hemophilia is a bleeding disorder of varying severity that is due to a deficiency in specific clotting factors. Normally the body responds to an injury that causes bleeding through a complex defence system. This consists of local changes in the damaged blood vessels, activation of blood cells called platelets, and the coagulation (clotting) process. Most inherited bleeding disorders are the result of abnormal platelet function or a deficiency in one or more of the factors involved in the blood clotting system.

Hemophilia is the most common inherited coagulation factor deficiency. Hemophilia A is a result of a deficiency of factor VIII, and hemophilia B of factor IX. Hemophilia A is more common than hemophilia B, and varies in severity depending on the level of factor VIII activity. Hemophilia B  is often a severe bleeding disorder.

How is hemophilia inherited?
Hemophilia is an X-linked,recessive disorder.  It is one of the few sex-linked traits in dogs. Because males have only 1 X chromosome, a male dog is either affected or clear of the defect. Females, with 2 X chromosomes, may be affected (abnormal gene on both chromosomes), clear, or a carrier with no clinical signs (one gene affected). In effect, the disease is carried by females but affects mostly males.

What breeds are affected by hemophilia?
The disease occurs in many different breeds and in mixed breed dogs as well. The German shepherd is the breed most commonly affected.

For many breeds and many disorders, the studies to determine the frequency in the breed have not been carried out. We have only listed breeds for which there is a strong consensus among those investigating in this field and among veterinary practitioners, that the condition is significant in this breed.

What does hemophilia mean to your dog & you?
Dogs with mild forms of hemophilia may experience few or no signs, and may never require treatment until/unless surgery or trauma is followed by excessive bleeding.

Where hemophilia is more severe, you may see signs of a problem at a fairly early age. Your pup may have prolonged bleeding associated with the loss of baby teeth, or unexplained areas of bleeding under the skin. Bleeding into muscles or joints will often cause lameness.

Once the condition is diagnosed, your veterinarian will discuss ways to manage this lifelong problem. These include being alert for signs of bleeding episodes in your dog, and tips on housing and maintenance so as to minimize risks of bleeding. Periodic blood transfusions will generally be required.

Unfortunately, dogs with severe hemophilia often die or are euthanized because of recurrent or uncontrollable bleeding problems.

How is hemophilia diagnosed?
The clinical signs associated with hemophilia vary widely, based on the severity of the bleeding disorder and where in the body the bleeding occurs. Because this is a sex-linked disorder, dogs with hemophilia are almost always male. Affected dogs are commonly brought to the veterinarian for problems such as bloody diarrhea that is difficult to control, areas of bleeding under the skin, or lameness (due to bleeding into muscles or joints).   Bleeding under the skin or into the muscle may occur after routine vaccination, or there may be prolonged or severe bleeding at surgery (such as when your dog is neutered.) Other less common problems include respiratory difficulties due to bleeding into the chest or around airways, or  weakness, paralysis, or even sudden death due to bleeding into the brain or spinal cord.

Once a bleeding disorder is suspected, specialized laboratory tests are carried out to diagnose the specific disorder. If your pup is diagnosed with hemophilia, it is important that you inform the breeder so that he or she can have your dog's parents tested. (The mother is likely a carrier and the father free of the defect.)   

For the veterinarian:

CLINICAL: Signs are highly variable and often non-specific: unthriftiness, acute blood loss anemia, unexplained sub-cutaneous masses, hematomas (often at injection sites), refractory bloody diarrhea. Other signs depend on the local physiologic impact of hemorrhage:  for example bleeding into the brain or around nerve trunks will cause neurologic signs, and bleeding around airways or into the pleural cavity will cause respiratory signs. Lameness is commonly associated with hemorrhage into muscles or joints, especially in larger breeds.

LABORATORY: normal PT (prothrombin time) and prolonged aPTT (activated partial thromboplastin time); definitive diagnosis requires a specific assay for factors VIII and IX. Factor activity will be markedly decreased. Specific factor assays are also required to screen for female carriers (heterozygotes), who usually have about 40 to 60% of normal factor activity. Consult your diagnostic laboratory for specific information about sample collection and submission.

How is hemophilia treated?
There is no cure for this disorder. Mildly affected dogs may never require treatment, or only after surgery or trauma.

With more severe hemophilia, your dog will require periodic transfusions when bleeding occurs, to replace the deficient coagulation factor activity. Strict cage rest is important along with transfusion, to decrease further hemorrhage.

For the veterinarian:
Administer fresh plasma, fresh frozen plasma, or cryoprecipitate (factor VIII) or cryosupernatant (factor IX) plasma. Transfused factors have a relatively short half-life so plasma may need to be transfused every 8 to 12 hours until the bleeding stops. Fresh whole blood may be used but it must be carefully cross-matched to prevent future transfusion reactions.

Breeding advice
Because hemophilia is a sex-linked recessive trait and the carrier state can be detected by testing, this disorder can be controlled. German shepherd females and females from lines of other breeds where hemophilia has been diagnosed, should be tested for the carrier state. Males used for breeding should be screened for the disorder.

FOR MORE INFORMATION ABOUT THIS DISORDER, PLEASE SEE YOUR VETERINARIAN.

Resources
Brooks,M. 1998. Hereditary bleeding disorders. ACVIM-Proceedings of the 16th Annual Veterinary Medical Forum: 424-426.

Copyright © 1998 Canine Inherited Disorders Database. All rights reserved.
This database is funded jointly by the Animal Welfare Unit at the Atlantic Veterinary College, University of Prince Edward Island, and the Canadian Veterinary Medical Association.

Permission to reprint is granted  by
Alice Crook, DVM Coordinator, Sir James Dunn Animal Welfare Centre
Atlantic Veterinary College University of Prince Edward Island


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