{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T17:07:56Z","timestamp":1787504876425,"version":"build-2736575974"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T00:00:00Z","timestamp":1771545600000},"content-version":"vor","delay-in-days":234,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,6,5]],"date-time":"2025-06-05T00:00:00Z","timestamp":1749081600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,7,1]]},"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n A 7-month-old female spayed English Springer Spaniel (ESS) was evaluated for spontaneous hemoperitoneum. Hyperfibrinolysis was identified on thromboelastography.<\/jats:p>\n <\/jats:sec>\n \n Hypothesis\/Objectives<\/jats:title>\n To identify a genetic mutation causing congenital hyperfibrinolysis in the proband and evaluate the prevalence of the mutation in the ESS breed.<\/jats:p>\n <\/jats:sec>\n \n Animals<\/jats:title>\n Client-owned ESS with hemorrhage and a non-affected littermate. Samples of DNA from 3 ESS, 1 Welsh Springer Spaniel (WSS) with unexplained hemorrhage, and 199 ESS with no history of hemorrhage.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n Whole genome sequencing (WGS) of the proband with variant filtering against an in-house WGS database of 671 presumably unaffected dogs identified a deleterious variant of SERPINE1 unique to the proband, which encodes for plasminogen activator inhibitor 1 (PAI-1). SERPINE1 was genotyped in the remaining animal population by Sanger sequencing or a Taqman assay. Liquid chromatography tandem mass spectrometry (LC\u2013MS\/MS) was performed on platelet pellets from the proband, a littermate, and three unrelated healthy ESS.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n Whole genome sequencing of the proband identified a unique homozygous insertion at chr6:8640592 in exon 1 of SERPINE1, which is predicted to cause a premature stop codon. The unaffected littermate was heterozygous for the mutation. Two unrelated ESS and 1 WSS with post-operative hemorrhage were homozygous for the mutation. Absence of PAI-1 in the proband's platelets was documented using LC\u2013MS\/MS.<\/jats:p>\n <\/jats:sec>\n \n Conclusions and Clinical Importance<\/jats:title>\n This novel mutation in SERPINE1 is associated with the absence of the PAI-1 protein in platelets and might cause hemorrhage because of hyperfibrinolysis in ESS and related breeds.<\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/jvim.70150","type":"journal-article","created":{"date-parts":[[2025,6,5]],"date-time":"2025-06-05T05:49:00Z","timestamp":1749102540000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Identification of a Novel Mutation in the SERPINE1 Gene Causing Clinical Hyperfibrinolysis in English Springer Spaniel Dogs"],"prefix":"10.1093","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-1575-6182","authenticated-orcid":false,"given":"Kelley","family":"Kilpatrick","sequence":"first","affiliation":[{"name":"School of Veterinary 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