Recessive X-linked coagulopathy due to deficiency of coagulation factor VIII, which prolongs the intrinsic pathway and predisposes to spontaneous haemorrhages or those following minimal trauma. Males (hemizygotes) are the typically affected and females are usually asymptomatic carriers. Severity depends on the variant and on residual factor VIII activity. It is due to mutations of the F8 gene, with breed-specific variants.

Breeds with a documented F8 variant: Bobtail (Old English Sheepdog), Boxer, German Shepherd (two variants described) and Rhodesian ridgeback. Because of its X-linked pattern, the mutations tend to remain confined to isolated pedigrees and to be self-limiting. No stable reliable population frequencies are published; cases are sporadic but recurrent in these breeds.

- Bruising easily after minor trauma or surgery\n- Prolonged haemorrhages and spontaneous epistaxis\n- Lameness due to haemarthroses and joint/muscle bleeding\n- Prolonged aPTT with normal PT and von Willebrand\n- Factor VIII activity < 1 % in severe forms\n- Typical involvement of males; carrier females generally asymptomatic

Canine haemophilia A was recognised in research colonies (inversion of intron 22 of F8 in Miniature Schnauzer and Irish setter) as a model of the human disease. Subsequently, breed-specific point variants have been identified: in the German Shepherd a nonsense mutation in exon 1 (c.98G>A, p.W33*) and a missense in exon 11 (c.1643G>A, p.C548Y); in the Boxer a missense in exon 10 (c.1412C>G, p.P471R); in the Bobtail (Old English Sheepdog) a nonsense in exon 12 (c.1786C>T, p.R577*); and in the Rhodesian ridgeback an insertion of a SINE element in exon 14 of F8. Each finding has enabled genetic tests directed at the corresponding breed.

- Test breeding females and males related to cases with the F8 test specific to their breed\n- Do not breed affected males or known carrier females\n- The male offspring of a carrier female have a 50 % risk of being affected; all daughters of an affected male are obligate carriers\n- A clear male × clear female generates no risk; daughters of an affected male with a clear female will be carriers and the male offspring clear\n- Exclude affected males and carrier females from breeding, and record the lineage to prevent spread of the allele

Differential diagnosis with haemophilia B (factor IX deficiency, also X-linked), von Willebrand disease (autosomal) and anticoagulant rodenticides. The haemostatic work-up (aPTT, FVIII activity, FVIII antigen) guides; confirmation is molecular with the breed variant. In severe forms, infusion of factor VIII or plasma controls bleeding episodes; monitor for the appearance of inhibitor antibodies after treatment. Life expectancy can be normal if there are no severe haemorrhages.

1. Christopherson PW et al. (2014) Two novel missense mutations associated with hemophilia A in a family of Boxers, and a German Shepherd dog. Vet Clin Pathol 43(3):312-316. PMID: 25040606
2. Lozier JN et al. (2016) Severe hemophilia A in a male Old English Sheep Dog with a C to T transition that created a premature stop codon in factor VIII. Comp Med 66(5):405-411. PMID: 27780008
3. Kehl A et al. (2021) A SINE insertion in F8 gene leads to severe form of hemophilia A in a family of Rhodesian ridgebacks. Genes (Basel) 12(2):134. PMID: 33494213
4. Mischke R et al. (2011) Canine haemophilia A caused by a mutation leading to a stop codon. Vet Rec 169(19):496b. PMID: 21949058
5. Hough C et al. (2002) Aberrant splicing and premature termination of transcription of the FVIII gene as a cause of severe canine hemophilia A. Thromb Haemost 87(4):659-665. PMID: 12008949
6. Lozier JN et al. (2002) The Chapel Hill hemophilia A dog colony exhibits a factor VIII gene inversion. Proc Natl Acad Sci U S A 99(20):12991-12996. PMID: 12242334
7. Brockmann M et al. (2023) Hemophilia A in a litter of Border Collies caused by a one base pair deletion in the F8 gene. Vet Clin Pathol 52(4):607-612. PMID: 38104983
8. Hytönen MK et al. (2023) A frameshift deletion in F8 associated with hemophilia A in Labrador Retriever dogs. Anim Genet 54(5):606-612. PMID: 37438956
9. OMIA:000437-9615. Haemophilia A in Canis lupus familiaris. https://omia.org/OMIA000437/9615/