Genetic basis - Glanzmann’s Thrombasthenia (GT) is caused by mutations in genes encoding the platelet membrane glycoprotein complex αIIbβ3 (GPIIb/IIIa). In Great Pyrenees dogs, GT results from a 14-base insertion mutation in exon 13 of the ITGA2B gene encoding the αIIb subunit, causing a frameshift and premature stop codon. The mutation leads to either absence or severe deficiency of αIIbβ3 platelet receptors. The disease is inherited in an autosomal recessive pattern; affected dogs have two copies of the defective allele, while carriers have one copy and are asymptomatic.
Pathophysiology - Lack or dysfunction of αIIbβ3 integrin impairs platelet aggregation because it is the fibrinogen receptor essential for platelet-to-platelet binding. This defect causes impaired clot formation and defective platelet plug formation, increasing bleeding tendency. Symptoms typically manifest early (3-6 months old) with abnormal bleeding risks.
Complications - Spontaneous bleeding (petechiae, mucous membrane hemorrhages). Excessive bleeding after trauma, surgery, or tooth eruption. Nosebleeds (epistaxis), gingival bleeding, and superficial skin hemorrhages are common. Bleeding episodes can be severe and life-threatening without prompt treatment. Blood transfusion/support may be needed after injury or surgery; no specific cure exists.
Why This Matters to Breeders and Vets - For breeders, avoiding affected matings prevents producing puppies with a serious bleeding disorder, improving animal welfare and reducing veterinary costs. For veterinarians, understanding GT allows early diagnosis and management of bleeding episodes and informs prognosis. Awareness of the genetic cause helps with genetic counseling for breeders and owners. Knowledge of autosomal recessive inheritance supports strategic breeding decisions to reduce disease frequency.