Test Detail

Hereditary bleeding disorder of the German Shepherd caused by a defect in the exposure of procoagulant phosphatidylserine (PS) on the platelet membrane after activation. Platelets show normal aggregation and secretion, but are unable to externalise PS and form 'coated' platelets (coated-platelets), which prevents thrombin generation and explains the bleeding. The clinical picture is a mild to moderate haemorrhagic diathesis discovered after trauma or surgery.

Specific to the German Shepherd. Reliable population frequency data are limited; the allele is concentrated in lines derived from the initial colony. It does not appear to be common outside the breed.

- Prolonged bleeding after surgery, trauma or tooth extraction\n- Spontaneous petechiae and ecchymoses on mucous membranes\n- Recurrent mucocutaneous haemorrhages\n- Muscle haematomas after minor exertion\n- 'Normal' coagulation and platelet aggregation in routine tests\n- Normal prothrombin and thromboplastin times

Brooks and colleagues described in 2002 a colony of German Shepherds with hereditary haemorrhagic diathesis and platelets unable to externalise PS after activation, a phenotype overlapping with human Scott syndrome. Linkage mapping in 2010 (Brooks et al.) localised the locus to canine chromosome 27 (CFA27). In 2015, the same group identified the causal variant: a splice mutation g.8912219G>A in TMEM16F (also called ANO6), which removes the TMEM16F protein from the platelet membrane and prevents calcium-dependent scramblase activity. The canine model has become a reference for studying the role of TMEM16F in haemostasis.

- Test breeding animals before mating, especially in lines with a history of bleeding\n- Do not mate two carriers: 25% risk of affected homozygotes\n- A carrier can be mated to a clear animal; offspring intended for breeding must be tested\n- For scheduled surgery in an untested dog, inform the veterinarian so that blood products are available\n- Progressively replace carriers with clear offspring without narrowing the gene pool

The differential diagnosis includes immune thrombocytopenia, von Willebrand disease (more common in the German Shepherd, especially type I vWD) and coagulation cascade defects. Routine tests (PT, aPTT, count, aggregometry) may be normal and mask the defect; diagnosis requires genetic testing or PS exposure assays by flow cytometry with annexin V. Treatment of bleeding episodes requires platelet or plasma transfusion; antifibrinolytics help as an adjunct.

1. Brooks MB et al. 2015. A TMEM16F point mutation causes an absence of canine platelet TMEM16F and ineffective activation and death-induced phospholipid scrambling. J Thromb Haemost 13:2240-2252. PMID: 26414452
2. Brooks MB et al. 2010. A genome-wide linkage scan in German shepherd dogs localizes canine platelet procoagulant deficiency (Scott syndrome) to canine chromosome 27. Gene 450:70-75. PMID: 19854246
3. Donner J et al. 2023. Genetic prevalence and clinical relevance of canine Mendelian disease variants in over one million dogs. PLoS Genet 19(2):e1010651. PMID: 36848397
4. OMIA:001353-9615. Scott syndrome, ANO6/TMEM16F-related, perro.