Glanzmann Thrombasthenia Great Pyrenees Type (GT)

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Acronyms: GT
Gene: ITGA2B
Mutation: Insertion
Mode of inheritance: Autosomal recessive
Breeds: Pyrenean Mountain Dog

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Product Description

Glanzmann Thrombasthenia Great Pyrenees type (GT)

Glanzmann Thrombasthenia Great Pyrenees type (GT) is a form of thrombasthenia,a bleeding disorder affecting the Great Pyrenees dog. Glanzmann Thrombasthenia is affecting also Otterhound breed and disorder with similar symptoms but different genetic cause has been identified in Finnish Spitz and Basset Hound. Glanzmann Thrombasthenia has been reported also in humans and horses. The defect was for the first time described by Edward Glanzmann in 1918, but biochemical basis and genetic mutation for the defect was not known until late 20th century. GT can be divided into three groups, which differ among each other in the quantity of the specific platelet membrane glycoproteins known as αIIb  and b3, or collectively as the fibrinogen receptor. In this way, GT can be divided into type I, type II and variant GT. Type I is characterized by severe quantitative deficiency, type II by moderate quantitative deficiency and variant by relatively normal quantity but reduced function.

Platelets are also known as thrombocytes and their main function is prevention of bleeding by clumping or clotting blood vessel injuries.  In healthy platelet integrin αIIb b3 integrin is required, which is abundant in healthy platelets. This integrin binds fibrinogen (factor I), a glycoprotein required for formation of blood clots. Other than platelet aggregation, αIIb b3 integrin has other roles, such as transmembrane signaling and uptake of fibrinogen for storage in platelets.

Symptoms and Characteristics

GT is a bleeding disorder, or coagulopathy, in which platelets contain defective or low levels of αIIb b3. Low levels of this glycoprotein disable binding of fibrinogen and consequentially platelet aggregation cannot occur. The first time that type I GT was diagnosed in a dog, conclusion was based on results provided from platelet function studies, flow cytometry, immunoblots and autoradiography of two-dimensional gel electrophoresis.

The disorder in dogs is characterized by prolonged bleeding time and formation of hematomas at sites of injury. Other manifestation of the disease includes purpura, epistaxis, gingival hemorrhae with trauma associated with chewing rawhide and petechial hemorrhages on buccal mucosa and sporadically on the abdomen. Affected dog appears to be smaller than what is common for the breed, due to enhanced iron demands during growth. However, providing oral iron was shown to be ineffective in preventing iron deficiency until the dog’s iron demands required for growth had diminished. Epistaxis and melena are common among affected dogs. The dog will have also prolonged clotting times post-operatively. When observing blood smears of an affected dog, 30% to 80% of all platelets are seen as bizarre and giant.

While establishing a diagnosis of Glanzmann Thrombasthenia, other common bleeding causes are being taken in consideration as well, such as Von Willebrand’s disease, anticoagulant rodenticides, aplastic pancytopenia, hemangiosarcoma and Waldenström’s macroglobulinemia.

Genetics

Glanzmann Thrombasthenia Great Pyrenees type (GT) is caused by a mutation in the gene encoding for platelet glycoprotein subunit αIIb. The GT disorder is inherited in an autosomal recessive manner.  Healthy parents of an affected puppy are obligate heterozygotes, and therefore carry one mutant allele. Heterozygotes have no symptoms. Dogs homozygous for the mutation will display the symptoms of the Glanzmann Thrombasthenia Great Pyrenees type (GT). At conception, each cub has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier.

References:

Lipscomb DL, Bourne C, Boudreaux MK. (2000): Two genetic defects in alphaIIb are associated with type I Glanzmann’s thrombasthenia in a Great Pyrenees dog: a 14-base insertion in exon 13 and a splicing defect of intron 13. Vet Pathol. 37(6):581-8.

Boudreaux MK, Kvam K, Dillon, AR, Bourne C, Scott M, Schwartz KA, Toivio-Kinnucuan M. (1996): Type I Glanzmann’s thrombasthenia in a Great Pyrenees dog. Vet Pathol. 33(5):503-511.

Boudreaux MK, Lipscomb, DL. (2001): Clinical Biochemical, and Molecular Aspects of Glanzmann’s Thrombasthenia in Humans and Dogs. Vet Pathol. 38: 249-260.