[ENROLLMENT CLOSED] Comparison of DEPOHGEN and Functional Coagulation and Fibrinolysis Tests in IWs

A previous study in Irish Wolfhounds (IWs) funded by the IWF showed that, compared to age and sex matched control dogs, IWs have evidence of weaker blood clot formation and faster blood clot breakdown. This may, in part, explain the results of a 2019 survey of IW owners that showed a high incidence of excessive bleeding post-operatively and after traumatic events. Recently, a genetic mutation has been identified in Scottish Deerhounds that is associated with delayed postoperative bleeding (the delayed postoperative hemorrhage gene, DEPOHGEN). The IWF tested a cohort of 94 IWs at the National Specialty in 2023 and found that 24% had 2 copies of the mutated gene, 52% had one copy of the mutated gene, and only 24% had 2 copies of the normal gene. The protein encoded by this gene (α2-antiplasmin) inhibits plasmin, the primary enzyme that breaks down blood clots. If the mutations present in IWs decrease the function of this enzyme, this could predispose them to increased clot breakdown and bleeding, especially in
the postoperative period. We will investigate whether α2-antiplasmin has decreased activity in IWs with this mutation compared to IWs without it. In addition, we will investigate whether plasma-based tests of blood clot formation (prothrombin time, activated partial thromboplastin time, and fibrinogen) and whole blood tests of overall blood clot formation and breakdown (Viscoelastic Coagulation Monitoring) are different between IWs with and without the mutation. If we can demonstrate an association between the mutation and functional blood clot formation and/or breakdown, this would provide a rationale for prophylactic treatment of Irish Wolfhounds
undergoing surgery with clot stabilizing drugs (such as aminocaproic acid and tranexamic acid), as well as a foundation for future clinical trials to determine their effectiveness. We will use blood samples from 60 previously genotyped IWs (20 with 2 copies of the DEPOHGEN mutation, 20 with 1 copy, and 20 with 2 copies of the normal gene) and run a battery of tests to determine if the mutation is associated with measurable changes in blood clot formation and/or breakdown.

Additional Study Details

Study Date(s): 07-10-2023
Study Status: Ongoing
Enrollment Status: CLOSED to new enrollment
Lead Researcher(s): Daniel J. Fletcher, PhD, DVM, DACVECC

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