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Coagulopathies: Why DNA test your dog

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Bleeding abnormalities  (coagulopathies) in dogs can occur for a variety of reasons: Infection, organ failure, toxins—or they can be caused by an inherited abnormality in the coagulation pathway. Although some breeds are known to have a higher incidence of blood disorders, coagulopathies can affect breeds of all types and sizes—from Doberman Pinschers to Shetland Sheepdogs,...

Coagulopathies: Why DNA test your dog

Bleeding abnormalities  (coagulopathies) in dogs can occur for a variety of reasons: Infection, organ failure, toxins—or they can be caused by an inherited abnormality in the coagulation pathway. Although some breeds are known to have a higher incidence of blood disorders, coagulopathies can affect breeds of all types and sizes—from Doberman Pinschers to Shetland Sheepdogs, Boxers to German Shepherd Dogs—and they can be extremely complex.

To help you stay ahead of any issues, we asked our veterinary geneticists to do a deep dive into the causes, diagnostic tests, and treatments for canine coagulopathies, as well as the genetic variants Embark can test for with just one cheek swab. It’s an easy, non-invasive and cost-effective way to determine if your dog is at risk for a specific coagulopathy—so you and your veterinarian can focus on monitoring and a potential treatment plan. Let’s dive in.

What’s normal: The stages of hemostasis

Hemostasis, the term that refers to stopping the flow of blood after blood vessel damage, has a primary and secondary stage. 

  • Formation: Primary hemostasis involves the formation of a platelet plug (platelet cells are one part of the blood’s ability to clot properly). 
  • Stabilization: Secondary hemostasis involves the stabilization of the platelet plug with fibrin (mesh-like strands) and other agents. This stage also includes fibrinolysis, which refers to the eventual breakdown of the clot to allow completion of healing and renewal of normal blood flow. If this breakdown is too rapid, abnormal bleeding can occur. 

What’s abnormal: Bleeding disorder types

Bleeding issues can occur at either stage. Primary hemostatic disorders, which often are visible as bruising or small dark spots on the skin or gums, occur when platelets fail to properly form the plug. Secondary hemostatic disorders, which may manifest as a large hematoma, or bleeding into a body cavity such as the abdomen or joints, occur when clot stabilization fails for reasons including a deficiency of one or more coagulation factors. Both types may be hereditary or acquired.

Primary hemostatic disorders

Causes: Platelet plug formation failure may be due to a low platelet count (thrombocytopenia), poor platelet function (thrombopathia), or a von Willebrand Factor abnormality.

    • Low platelet count may be due to non-genetic factors such as autoimmune disease, infections (often transmitted by ticks), and bone marrow abnormalities including estrogen toxicity (typically from exposure to human medications). A genetic condition, Cyclic Hematopoiesis of Gray Collies is characterized by recurring fluctuations in the number of circulating platelets and other blood cells. Embark is further exploring “Gray Collie Syndrome”, and we would appreciate the submission of blood work from any clinically affected dogs. Please email breeders@embarkvet.com with submissions.
    • Poor platelet function may be hereditary or caused by non-genetic factors like kidney disease or non-steroidal anti-inflammatory medications.
    • von Willebrand Disease (vWD), which affects Dobermans and other breeds, is an inherited coagulopathy caused by reduced or non-functional von Willebrand Factor (vWF), a blood protein needed to control bleeding at the site of injury by impacting platelet function. vWD can take one of 3 forms:
      • Type I is associated with a low level of vWF and variable bleeding. It occurs in Doberman Pinschers, Pembroke Welsh Corgis, Poodles, Bernese Mountain Dogs, and other breeds. A genetic variant test is available for some forms. 
      • Type II is associated with a low concentration of vWF with an abnormal structure and tends to cause severe bleeding. There is a genetic variant test applicable for German Shorthaired Pointers and German Wirehaired Pointers. 
      • Type III is associated with markedly reduced (or absent levels) of vWF and severe bleeding. There are known genetic variants in several breeds such as Scottish Terriers, Shetland Sheepdogs, and Dutch Kooikers.

Clinical signs: Primary hemostatic disorders impact the skin or mucous membranes and may be noted by an owner or veterinarian as ecchymoses (bruising), petechiae (small dark spots), epistaxis (nose bleeds), frank red blood in vomit, the stool, or urine, or as black digested blood in the stool, also called melena.

Diagnosis & testing: Diagnosing a primary hemostatic disorder may require a combination of genetic screening, a physical examination, history, and veterinary tests. Tests for primary hemostatic disorders may include the following; see all the variants Embark tests for here.

  • Genetic tests
    • Macrothrombocytopenia (TUBB1): Embark provides genetic variant testing for Macrothrombocytopenia (large platelets in low numbers), a hereditary condition with  a causative genetic variant that affects Cairn and Norfolk Terriers. While platelet numbers appear low on blood counts, affected dogs are usually asymptomatic. This test can help rule in or rule out a genetic cause of low platelet number. A different variant also exists in the Cavalier King Charles Spaniel. If you have a CKCS with blood work that shows Macrothrombocytopenia, please let us know at breeders@embarkvet.com
    • von Willebrand Disease: Embark tests for this disorder across a variety of breeds. Genetic screening provides valuable non-changing insight, since plasma (blood) vWF levels fluctuate daily in normal, healthy dogs, and may be exaggerated during pregnancy or heat in bitches and in any dog with a systemic illness.
    • P2Y12 Platelet Disorder: Embark tests for this receptor platelet disorder in Greater Swiss Mountain Dogs. Interestingly, P2Y12 is the same receptor targeted by platelet inhibiting drugs in people at risk for cardiovascular disease; thus, spontaneous bleeding is not expected unless there are other contributing factors such as survergy or trauma.
    • Glanzmann’s Thrombasthenia (ITGA2B): Embark tests for this disorder of platelet aggregation in Otterhounds.
    • Thrombopathias: Embark tests for these disorders of platelet function in American Eskimo Dogs, Basset Hounds, and Newfoundlands, and symptoms can range from mild to severe.  
  • Non-genetic tests
    • Complete blood count (CBC): Platelet number and size are reviewed by machine and under a microscope in a veterinary hospital or outside laboratory to identify abnormalities. 
    • Buccal mucosal bleeding time (BMBT): Veterinarians test platelet function with a BMBT; this is often performed secondary to a known genetic risk for von Willebrand Disease (vWD).
    • Von Willebrand Factor antigen assay (vWF:Ag): This test, which is performed at an outside lab, measures the concentration of vWF in a blood sample and compares it to a standard. (In general, the most severely affected dogs have a marked reduction in plasma vWF:Ag with values of <15%). This test should be performed secondary to a genetic risk for von Willebrand Disease.

Treatment: Primary hemostatic disorders are generally treated by lifestyle management and risk mitigation.

Depending on the underlying cause, your vet may also prescribe or administer medication such as antibiotics, immunosuppressive drugs, immunomodulators, StablePlate Rx, or blood products such as platelet-rich plasma, fresh plasma, or cryoprecipitate. A dog with Type I vWD may also be prescribed desmopressin acetate (DDAVP), which stimulates release of vWF from stores, increases vWF:Ag values, and decreases the BMBT for up to 4 hours. (DDAVP does not work in dogs with Type III vWD as they lack these stores of vWF, and not all dogs with Type I vWD will respond to the drug.)

Secondary hemostatic disorders

Causes: Secondary hemostatic abnormalities, or failure of the platelet plug to stabilize, can have genetic or non-genetic causes.

  • Genetic causes: The most common inherited defect of secondary hemostasis is hemophilia—a group of coagulation factor deficiencies that may cause dogs to bleed spontaneously. Embark tests for genetic variants known to cause Factor VIII deficiency in Boxers and German Shepherd Dogs, Factor IX deficiency in Cairn Terriers and Rhodesian Ridgebacks, and Factor VII deficiency in several breeds. Here is more information about some of those factor deficiencies and other causes of secondary hemostatic disorders:
    • Factor VIII deficiency (Hemophilia A): Factor VIII has a recessive X-linked mode of inheritance, making it more common to be clinically expressed in males. (Males have only one X chromosome and thus they either have a normal copy of the gene or the variant: If they have the variant, they will be considered at risk.) Females have two X chromosomes and typically must inherit two abnormal copies to be at risk from the variant.  Learn more. The severity of clinical signs range from mild to severe, depending on the degree of  deficiency in Factor VIII. The condition may even go unrecognized unless excessive bleeding occurs due to surgery or trauma.
    • Factor VII deficiency: This deficiency, which has been recognized in Beagles, Miniature Schnauzers, Alaskan Malamutes, Boxers, and Bulldogs, is not usually accompanied by detectable bleeding but affected individuals may have bruising or bleeding following surgery or postpartum. The genetic variant that causes Factor VII deficiency, is not X-linked (it is autosomal recessive), and there may also be breed-dependent penetrance of the genetic variant.
    • Prekallikrein deficiency (KLKB1): A causative genetic variant is known to occur in Shih Tzus. This deficiency creates abnormally long clotting times on a laboratory coagulation test (aPTT), but is not associated with clinical bleeding tendencies. Embark’s genetic variant testing can help determine if this is a benign cause of a prolonged aPTT.
    • Platelet Factor X Receptor deficiency (TMEM16F): Interestingly, while Scott Syndrome in German Shepherds is a defect in platelet function, it leads to impaired secondary hemostasis.
  • Non-genetic causes. These include liver dysfunction, toxicity from rodenticides that reduce active vitamin K (which is required for factors II, VII, IX, and X to be properly synthesized in the liver), and medication such as heparin and warfarin.

Clinical signs: As noted above, secondary hemostatic disorders can cause minimal clinical signs or severe bleeding. Spontaneous hematomas under the skin, blood in the joints, and blood in body cavities such as the lungs or abdomen, are common manifestations in affected dogs, particularly those with severe deficiencies.

Diagnosis & testing: Secondary hemostatic disorders are diagnosed based on a combination of genetic tests, veterinary physical exams, and other specialized laboratory testing that may include:

Genetic tests: Embark tests for variants known to cause secondary hemostatic abnormalities including Factor VIII deficiency, Factor VII deficiency, and Prekallikrein deficiency (KLKB1). To see the complete list of genetic variants for which Embark tests, click here.

Non-genetic tests

    • PT (prothrombin time): This test evaluates factors II, VII, IX, and X, which are not only vitamin-K dependent but also have the shortest half-lives. This test can be performed  in a veterinary hospital or outside lab.  
    • aPTT (activated partial thromboplastin time): This test evaluates factor XII, and it is not prolonged until there is < 25% factor function. As previously noted, the aPTT will be increased in dogs at risk from the KLKB1 variant. This test can also be performed in the veterinary hospital or at an outside laboratory.
    • Specific factor analyses: These tests measure the amount of specific factors such as VII and VIII. These almost always require analysis at a laboratory located outside of the veterinary hospital.
    • Blood chemistry: These tests provide a basic evaluation of liver and kidney function as well as protein levels. Specialized blood or urine testing may be indicated based on basic chemistry results.

Treatment: Treatment options depend on the underlying cause. Vitamin K administration may aid in mitigating issues with factors II, VII, IX, and X which are common in rodenticide toxicities. Fresh or fresh frozen plasma or cryoprecipitate may also be used to provide different coagulation factors or other clot stabilizers.

As mentioned, when clots break down too fast or too soon, bleeding can occur. This often manifests as delayed bleeding after a surgical procedure and is known to occur in Greyhounds 36-72 hours post-operatively. Aminocaproic acid, which stabilizes clots, may be given to Greyhounds prior to surgery.

Other causes of excessive bleeding

Illnesses such as cancers, acute pancreatitis, gastric dilatation and volvulus (bloat or GDV), sepsis, snakebites, and hypo/hyperthermia can all lead to excessive bleeding by depleting proteins and platelets involved in blood clotting. While not an independent disease, this type of excessive bleeding is often referred to as disseminated intravascular coagulopathy (DIC) and is a serious veterinary emergency.

What’s next

Identifying and managing hemostatic abnormalities in dogs is complex: There are a wide range of tests that can aid in a diagnosis, and genetic testing and research are valuable pieces of the puzzle. As a science-driven company that enables research, Embark is committed to doing more.

We encourage breeders and owners to keep us in the loop by filling out our surveys to provide us with any diagnosis of a coagulopathy. And we make it possible for you to contribute to ongoing research. With every Embark-tested dog that is opted into research, new data are added to our database. These massive data resources uniquely position Embark to better understand the genetic causes of primary and secondary hemostatic disorders so we can empower breeders to avoid producing at risk puppies. Together with our breeders, breed clubs, scientists, and our research partner the Cornell University College of Veterinary Medicine, we can continue to make discoveries that improve the lives of dogs. Learn about all our research projects here.

For more information about blood disorders, visit:

https://eclinpath.com/hemostasis/disorders/inherited-coagulation/

https://www.vet.cornell.edu/animal-health-diagnostic-center/laboratories/comparative-coagulation/clinical-topics

 

Lisa Peterson Contributor

Award-winning writer, journalist, and podcast host, Lisa Peterson, is a canine subject matter expert and Senior Content Strategist, Breeder/Veterinarian at Embark Veterinary. She served as the American Kennel Club director of communications and club communications for 10 years before becoming a Westminster Kennel Club public relations consultant from 2016 to 2021. Lisa began owning, breeding, and handling Norwegian Elkhounds more than 35 years ago, and today is an AKC judge and AKC Breeder of Merit.

Read more about Lisa Peterson

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