Hyperfibrinolysis in English Springer Spaniels and Welsh Springer Spaniels

Hyperfibrinolysis is the name for plasminogen activator inhibitor-1 (PAI-1) deficiency. It is a hemostatic disorder, and clinical signs are related to impaired blood clot stability. Spontaneous or postoperative bleeding, including severe bleeding into body cavities, is typical. Bleeding can occur without obvious trauma and often occurs at a young age.

The cause of the disease is the c.101dup mutation in the SERPINE1 gene, which encodes for protein called plasminogen activator inhibitor-1 (PAI-1), a key regulator of fibrinolysis. PAI-1 deficiency causes uncontrolled fibrin degradation, leading to blood clot instability and subsequent bleeding.

The mutation is inherited in an autosomal recessive manner. This means that the disease only develops in individuals who inherit the mutated gene from both of their parents. Carriers of the mutated gene are clinically healthy, but they pass the mutation to their offspring. In the case of mating two heterozygous individuals, theoretically 25% of the offspring will be clear (without the mutation), 50% of the offspring will be carriers, and 25% of the offspring will inherit the mutated gene from both parents and will therefore be affected by this disease.

A genetic test can clearly reveal the genotype of the animal and is a suitable tool for breeders to prevent the unintentional reproduction of affected puppies.

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References:

Kilpatrick, K., Cullen, J.N., Almeer, F.F., Higgins, L., Markowski, T., Brooks, M., Friedenberg, S.G., Racette, M. : Identification of a novel mutation in the SERPINE1 gene causing clinical hyperfibrinolysis in English Springer Spaniel dogs. J Vet Intern Med 39:e70150, 2025. Pubmed reference: 40470612