Rebecca
Chenoweth

Vet Med Summer Research Canine necropsy cases with unexplained hemorrhaging: investigation of von Willebrand disease type 1 variant

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Rebecca Chenoweth

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Canine necropsy cases with unexplained hemorrhage typically trigger anticoagulant toxicity testing in diagnostic laboratories. However, when these toxicity tests are negative, the bleeding etiology is not usually further pursued. DNA was previously extracted from banked tissues of canine necropsy cases with unexplained bleeding and negative anticoagulant tests (n = 62) or positive anticoagulant tests (auxiliary controls, n = 5). These dogs were genotyped for a Factor VII variant known to cause variable bleeding phenotypes in many breeds of dogs; all results were negative. As a next step, the present study investigated the known von Willebrand disease type I (vWDI) variant (c.7437G>A) in the same population. The mode of inheritance for vWDI is autosomal with incomplete penetrance, although the expressivity on different breed backgrounds is variable. To identify the vWDI variant, the DNA extractions were run through PCR and then submitted for Sanger sequencing. Four heterozygous dogs were identified in the sample population. Each of the identified carriers is from a breed known to possess the vWDI variant in its gene pool (German Shepherd, American Staffordshire Terrier, and Miniature Australian Shepherd) except for the Newfoundland. Our results provide a likely explanation for the bleeding phenotype observed in these four cases, however, the lack of von Willebrand's factor plasma quantification means this conclusion has some uncertainty. Incorporation of routine vWDI genotyping for such cases in the future may be reasonable depending on the dog's breed, although the likelihood of successful diagnostic resolution is moderate, given the rarity observed in our sample population.

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Purdue University / 2023

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Rebecca Chenoweth

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