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Congenital Platelet Function Disorders |  |
| Congenital disorders of platelet function affect platelet adhesion, aggregation, or secretion. They can be either intrinsic or extrinsic to platelets. Testing of intrinsic platelet function requires careful handling of samples and specialized equipment that is not routinely available in diagnostic laboratories; therefore, the incidence of intrinsic functional defects in platelets is not known accurately. However, if a bleeding disorder (especially mucosal bleeding or superficial
petechiation) exists in an animal that has not received any medication and that has normal coagulation screening test results, platelet concentration, and von Willebrand’s factor concentration, then an intrinsic platelet defect should be suspected. |
| Congenital Intrinsic Platelet Function Disorders: |
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Chédiak-Higashi syndrome (
Inherited Leukocytic Disorders) is an autosomal recessive disorder characterized by abnormal granule formation in leukocytes, melanocytes, and platelets. The defect appears to be in microtubule formation; therefore, granules, which are abnormally large but reduced in number, are evident in numerous types of cells. Diluted coat color results from the defect in the melanocytes. Leukocytes may have decreased functional ability to phagocytize
and kill organisms (an inconsistent finding in animals), and platelets have decreased aggregation and release reactions. Platelets are almost devoid of dense granules and have markedly decreased storage quantities of adenosine diphosphate and serotonin. Prolonged bleeding in affected blue smoke Persian cats occurs after venipuncture or surgery. The syndrome has been diagnosed in mink, cattle, and beige mice with similar bleeding tendencies. |
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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. Specific
diagnosis of this disorder requires specialized platelet function testing. Results of the clot retraction test are usually normal. |
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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. |
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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. |
| There is no specific treatment for any of the intrinsic platelet function disorders. In instances of severe hemorrhaging, fresh platelet-rich plasma can be administered. Whole blood may be administered if the affected animal is anemic. |
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| Congenital Extrinsic Platelet Function Disorders: |
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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. In the more common inheritance pattern of autosomal dominant with incomplete penetrance, homozygotes and heterozygotes
can have variable bleeding tendencies. 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. Von Willebrand’s factor circulates as a complex with coagulation Factor VIII (also called Factor VIII-coagulant) and mediates platelet adhesion to subendothelial surfaces—the first step in clot formation. Defective or deficient
von Willebrand’s factor mimics disorders caused by thrombocytopenia or intrinsic platelet defects. Von Willebrand’s disease should be suspected in animals with bleeding disorders that have normal results on coagulation screening tests and adequate platelet concentrations. Occasionally, affected animals may have decreased Factor VIII-coagulant and therefore have prolonged APTT and ACT. Quantitative tests of von Willebrand’s factor are diagnostic. Drugs known to interfere with
normal platelet function should be avoided in animals with suspected disease. Transfusion of fresh whole blood or fresh plasma (6-10 mL/kg) is effective in alleviating a bleeding episode. |
| Concomitant hemostatic abnormalities may exacerbate von Willebrand’s disease. Hypothyroidism (
Hypothyroidism) previously had been thought to be associated with von Willebrand’s disease; both conditions are prevalent in many of the same breeds of dogs, eg, Doberman Pinschers and Golden Retrievers. In one study, administration of thyroid supplementation to hypothyroid dogs without deficiency of von Willebrand’s factor did not increase von Willebrand’s factor
activity; in fact, in most of the tested dogs, the activity actually decreased. Therefore, administration of levothyroxine as a treatment of von Willebrand’s disease cannot be recommended and may even exacerbate the disease. |
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