Hereditary thrombopathy of the Greater Swiss Mountain Dog caused by a mutation in the P2RY12 gene, which encodes the platelet ADP receptor. Platelets from affected animals do not respond to ADP and therefore do not aggregate properly after activation. Homozygous dogs present mild spontaneous bleeding, but the serious risk appears after surgery or trauma, when the haemorrhage can be exsanguinating and fatal. It is the first P2RY12 gene defect described in a domestic species and constitutes the natural model of the equivalent human disorder (platelet disorder type 8).

Affected breed: Greater Swiss Mountain Dog. The mutant allele is relatively widespread in the breed ("widespread", Flores et al., 2017), although no reliable carrier frequency figures from large series have been published; it has not been detected in other breeds.

- Mild spontaneous bleeding (gingival bleeding during teething, epistaxis, cutaneous haematomas)\n- Severe or fatal bleeding after surgery (ovariohysterectomy, laparotomy) or trauma\n- Prolonged buccal mucosal bleeding time (BMBT) with normal platelets, PT, APTT and vWF\n- Absence of platelet aggregation in response to ADP on cytometry and aggregometry\n- Possible postoperative haemorrhagic peritonitis with tachycardia, pallor and falling haematocrit

The first case was described by Boudreaux and Martin in 2011 in a five-generation family of Greater Swiss Mountain Dogs: the index female bled massively after a routine ovariohysterectomy and required multiple transfusions. Flow cytometry studies showed platelets with normal expression of glycoproteins IIb/IIIa and normal response to convulxin and platelet-activating factor, but absent response to ADP. DNA analysis revealed a 3-base-pair deletion in P2RY12 that removes a conserved serine from the extracellular domain. In 2017, Flores and colleagues described a heterozygous female that also presented severe postoperative haemoperitoneum with platelet aggregation abolished in response to ADP, indicating that carriers are not exempt from risk.

- Test Greater Swiss Mountain Dog breeding animals with the P2RY12 test before the first mating\n- Do not mate two carriers: 25 % risk of affected homozygotes; also avoid mating an affected homozygote with a carrier\n- A carrier may be mated to a clear animal; the offspring intended for breeding should be tested\n- ALWAYS inform the veterinarian before any scheduled surgery (including neutering/spaying) of the animal's P2RY12 status, even if it is a carrier, and have blood products and desmopressin available\n- Consider the animal's status before tooth extraction and minor dental procedures\n- Exclude affected homozygous animals from breeding

Differential diagnosis with von Willebrand disease (the most common in dogs with postoperative bleeding) and with the thrombopathies of other breeds (e.g., GP defect in the Basset Hound, thrombasthenia in the Ottoman Shepherd). The distinguishing feature: normal platelets, PT, APTT and vWF, but abolished ADP aggregation. Flow cytometry with fibrinogen-FITC and ADP is decisive. Remember that a dog with prolonged BMBT and normal coagulation warrants suspicion of a thrombopathy. The mechanism by which a heterozygote may bleed is not clarified by the available sources.

1. Boudreaux MK, Martin M (2011). P2Y12 receptor gene mutation associated with postoperative hemorrhage in a Greater Swiss Mountain dog. Vet Clin Pathol 40(2):202-206. PMID: 21554368
2. Flores RS et al. (2017). Heterozygosity for P2Y12 receptor gene mutation associated with postoperative hemorrhage in a Greater Swiss Mountain dog. Vet Clin Pathol 46(4):569-574. PMID: 28800150
3. OMIA:001564-9615. Bleeding disorder, P2RY12-related in Canis lupus familiaris (dog).