Prekallikrein deficiency

Prekallikrein is a key protein in the intrinsic coagulation pathway, and its deficiency has been linked to the presence of specific genetic variants in the KLKB1 gene.

Symptoms

Prekallikrein deficiency is usually asymptomatic and, despite its involvement in the coagulation process, no increased bleeding tendency has been reported in affected dogs. Deficiency of other coagulation factors in combination with prekallikrein deficiency may eventually cause classic symptoms of hemostasis disorders such as hematuria. Clinically, affected dogs show a prolonged activated partial thromboplastin time (aPTT), indicating abnormal secondary hemostasis.

Disease Management

No specific preventive measures or cure are required for this condition.

Genetic basis

This disease follows an autosomal recessive mode of inheritance. Autosomal recessive inheritance means that the dog, regardless of sex, must receive two copies of the mutation or pathogenic variant to be at risk of developing the disease. Both parents of an affected dog must carry at least one copy of the mutation. Animals with only one copy of the mutation are not at increased risk of developing the disease, but may pass the mutation on to future generations. Breeding between dogs carrying genetic variants that can cause disease, even if they do not show symptoms, is not recommended.

Technical report

Prekallikrein is a plasma protein that regulates the activation of factors XI and XII in the intrinsic coagulation pathway. Prekallikrein deficiency has been associated with a variant identified in the KLKB1 gene, which involves the substitution of a nucleotide (c.988T>A) in exon 8, generating an amino acid change in a domain critical for the activation of another coagulation factor in humans. Deficiency of this coagulation factor is generally asymptomatic, however, it is important to note that more thorough research and a larger number of cases need to be addressed to fully understand the clinical implications of this association.

Most affected breeds

Shih Tzu
Shar Pei

Bibliography

Chinn DR, Dodds WJ, Selcer BA. Prekallikrein deficiency in a dog. J Am Vet Med Assoc. 1986 Jan 1;188(1):69-71. PMID: 3632973.

Okawa T, Yanase T, Shimokawa Miyama T, et al. Prekallikrein deficiency in a dog. J Vet Med Sci. 2011 Jan;73(1):107-11.