Test Detail

Hereditary thrombopathy characterised by giant platelets (macrothrombocytes) and moderate thrombocytopenia, caused by variants of the TUBB1 gene (β1-tubulin), a component of the platelet microtubule ring. The alteration prevents correct fragmentation of megakaryocytes and gives rise to large, few platelets. Platelet function is usually normal, so most animals do not bleed, but the finding on the automated haemogram can lead to erroneous diagnoses of severe thrombocytopenia. The validated causal variants have been described in the Cairn terrier, the Norfolk terrier and the Cavalier/King Charles spaniel.

Causal variants confirmed in Cairn terrier and Norfolk terrier (p.R2H) and in Cavalier/King Charles spaniel (p.D249N). Macrothrombocytopenia has been described in other breeds (e.g. Akita), but with no demonstrated relationship to TUBB1. Population allele frequencies are limited; relatively high rates have been described in some Cavalier King Charles spaniel lines.

- Test breeding animals of affected breeds with the TUBB1 test, especially in Cavalier King Charles spaniel\n- It is not necessary to systematically exclude carriers from breeding, since MTC does not usually cause clinically relevant bleeding\n- Avoid mating two affected homozygotes so as not to fix the macrothrombocytic phenotype\n- A carrier may be mated to a clear animal; offspring intended for breeding must be tested\n- Inform the veterinarian of the TUBB1 status so as not to confuse the thrombocytopenia with disease and to avoid unnecessary diagnostic tests

The most frequent diagnostic error is attributing the 'thrombocytopenia' on the automated haemogram to a serious disease (immune-mediated, infectious, bone marrow) when it is in fact hereditary macrothrombocytopenia: automated counters underestimate large platelets. The blood smear (or cytometry with an appropriate threshold) is key: it shows large platelets and a real count within range or only slightly low. Platelet function (aggregometry, BMBT) is usually normal. Do not confuse with functional thrombopathies (P2RY12 of the Greater Swiss Mountain Dog, GP defect of the Basset hound) which do cause haemorrhage.

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