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Coagulation Corner

Animals and Coagulation

Lions and Tigers and Bears, oh MY!

When I was a new tech, we had gotten a blood sample on a beached whale.  We performed a CBC and differential, it was loaded with eosinophils.  I remember the conversation when we gave the results, we were asked if that was normal.  Of course we had no idea what was normal for a whale.  Ever wonder what coagulation results are on animals?  Multispecies testing is fairly widespread.  Animals are used in safety testing for drugs, so it is important to understand what is normal to know what is abnormal.

It has been well established that coagulation data differ based on instrumentation and reagents.  Animal coagulation values differ from human values, even though they still have some of the same coagulation disorders.

For example:
Dogs present with hemophilia, FVII def., vWF disease, and  prekallikrein def.  Cats present with hemophilia, and FXII def.  While Horses can have hemophilia and pigs can have a Lupus anticoagulant.

Some of the disorders are manifested differently, for example bleeding occurs in animals with a prekallikrein deficiency, but not in humans.

Animals in relation to humans have shorter clotting times for the PT and APTT due to having higher factor concentrations.

Coagulation factors are produced in the liver.  Concentrations of factors are at different levels.

The APTT or PT (or both) are prolonged in 50-66% of dogs with liver disease, meaning that the factor activity is <30% of normal. Coagulation tests are often performed before liver biopsy. Severe hepatic diseases can also lead to disseminated intravascular coagulation. Fibrinogen, an acute phase reactant, and von Willebrand’s factor, which is produced extrahepatically, can be increased in liver disease.

Factor Deficiencies:
Factor VIII deficiency and factor IX deficiency are severe defects usually recognized as spontaneous hemorrhages before 10 weeks of age. Both are sex-linked recessive defects; males are clinically affected, whereas females are carriers and clinically normal.

• Von Willebrand disease is an autosomal defect , and both males and females are affected clinically. It is the most common inherited coagulation defect with high prevalence in many breeds.
• Factor X deficiency has been detected mostly in American cocker spaniels. It manifests as stillborn puppies or neonatal deaths related to internal hemorrhage. It is an autosomal defect with a severe defect in homozygotes, whereas heterozygotes may be clinically normal or have only a mild bleeding tendency.
• Factor XI deficiency is a rare defect described in English springer spaniels and a few dogs of other breeds. This autosomal defect is mild with bleeding after surgery or injury.
• Factor XII deficiency is fairly common in cats but is rarely detected because no bleeding tendency is associated with the defect.

In Disseminated intravascular coagulation (DIC) the syndrome is characterized by massive activation and consumption of coagulation proteins, fibrinolytic proteins, and platelets. This is the same in animals.  Death is caused by extensive microthrombosis or circulatory failure, leading to single or multiple organ failure. If the animal survives the acute DIC event, a chronic form of DIC can exist. Compensatory production of coagulation proteins and platelets by the liver and bone marrow, respectively, can alter the results of coagulation screening tests such that they may be within reference ranges or even shortened, and platelet concentrations may be normal. However, DIC can usually be identified by the presence of at least 3 abnormal coagulation test results. Horses, even in fulminant DIC, most often have hyperfibrinogenemia because their liver can produce much fibrinogen. Treatment should be directed toward correcting the underlying problem. Supportive care is essential. Administration of balanced electrolyte solutions to maintain effective circulating volume is imperative. Administration of heparin is controversial and should be accompanied by administration of plasma to assure adequate antithrombin III activity.

Platelets:
Platelet disorders affect platelet adhesion, aggregation or secretion. Horse platelets are the most responsive to ADP, whereas sheep are the most responsive to Ristocetin. Different responses suggest:

1. Structural differences  which include the composition of the platelet membrane as well as specific receptors to certain agonists.
2. Agonists that activate pathways with distinct signaling.

Regarding platelet activating factor (PAF) animal species platelets react distinctly different.  It appears that sheep and humans have a similar specific membrane receptor accounting for them having a similar response in comparison to other species. Platelet aggregation has been found to be steeper in rats compared to does dependent assays of other species. Bovine platelets respond only to ADP, collagen and thrombin and responses were significantly lower than human responses. While canines are significantly higher than humans.

Canine thrombopathia has been described in Basset Hounds. Affected dogs have epistaxis, petechiation, and gingival bleeding. Results of studies suggest that inheritance is autosomal with variable penetrance. Platelets have abnormal fibrinogen receptor exposure and impaired dense granule release. Basset Hounds with mucosal bleeding and petechiation and normal concentrations of platelets and von Willebrand’s factor should be suspected of having thrombopathia.

Bovine thrombopathia is an autosomally inherited platelet function defect seen in Simmental cattle. Bleeding can be mild to severe in affected cattle and is exacerbated by trauma or surgery. Platelets have impaired aggregation responses.

Thrombasthenic thrombopathia has been diagnosed in Otterhounds. It is autosomally transmitted. Affected dogs have prolonged bleeding times and form hematomas at sites of venipuncture or injury. Numerous (30-80% of all platelets), bizarre, giant platelets are seen on blood smears. Membrane glycoproteins II and III are reduced. Blood from affected dogs does not have normal clot retraction, and the platelets do not aggregate normally after stimulation with ADP, collagen, or thrombin.

Von Willebrand’s disease is caused by a defective or deficient von Willebrand’s factor (also called Factor VIII-related antigen). It is the most common inherited bleeding disorder in dogs (reported in nearly all breeds and in mixed breeds) and has also been reported in cats, rabbits, and pigs. The disorder is relatively frequent (10-70% prevalence) in several breeds of dogs: Doberman Pinschers, German Shepherds, Golden Retrievers, Miniature Schnauzers, Pembroke Welsh Corgis, Shetland Sheepdogs, Basset Hounds, Scottish Terriers, Standard Poodles, and Standard Manchester Terriers. Two modes of inheritance are known. In the less common autosomal recessive pattern of inheritance, homozygosity is usually fatal, and heterozygosity results in asymptomatic carriers.  Affected animals may have gingival bleeding, epistaxis, and hematuria. Some puppies may bleed excessively only after injection, venipuncture, or surgery, such as tail docking, ear cropping, and dewclaw removal.

So, as you can see many disorders for animals are similar to humans but may manifest itself differently in animals.  My dog had lupus when it was a puppy, it is just a self limiting viral disorder, she had lesions in her ears.  She is 13 now and has never had any reoccurrence of the disorder.  Understanding how disorders present and how platelets react in animals is important in treatment and in performing studies involving multispecies.

Donna Castellone

About the Author

Donna Castellone,
MS, MT(ASCP)SH
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