Factor XII deficiency

From Dog

Factor XII deficiency (Hageman factor) is a rare autosomal-dominant (incomplete penetrance) genetic form of canine hemophilia[1].

Factor XII upon contact with a negatively-charged surface undergoes autoactivation or cleavage by kallikrein and initiates the clotting cascade[2] by forming the active serine protease factor XIIa. Factor XII and the contact group play a physiologic role in promoting complement activation, inflammation, fibrinolysis and changes in vascular permeability[3].

Exogenous stimulation of canine factor XII by chemicals such as cholesterol, ellagic acid, rutin and E. coli endotoxin can predispose to vasculitis and cholecystitis in dogs[4].

Unlike factor VIII deficiency, this condition does not cause clinical bouts of acute hemorrhage and death due to this disease has note been reported.

Factor XII deficiency has been reported in the Shar Pei[5], German Short-haired Pointer, Basenji, Standard Poodle, Miniature Poodle.

Affected dogs are usually asymptomatic, although a predisposition to thromboembolism is possible. In some dogs, occasional bouts of hematochezia and diarrhea may be confused with ulcerative colitis, and occasional hematoma formation has been observed in otherwise asymptomatic dogs.

Urinalysis may reveal intermittent hematuria[6].

The condition is usually diagnosed incidentally during routine coagulation screening test, which shows prolonged partial thromboplastin and activated clotting times, but normal thrombin clotting time and fibrinogen concentration.

Concurrent factor XII and von willebrand's disease has been reported in Poodles[7], which presented with non-spherocytic hemolytic anemia but did not show bleeding tendencies.

Acquired factor XII deficiency has also been reported associate with brown spider envenomation[8].

References

  1. Fogh JM & Fogh IT (1988) Inherited coagulation disorders. Vet Clin North Am Small Anim Pract 18(1):231-243
  2. Mutch NJ et al (2012) Immobilized transition metal ions stimulate contact activation and drive factor XII-mediated coagulation. J Thromb Haemost 10(10):2108-2115
  3. Kitchens CS (2002) The contact system. Arch Pathol Lab Med 126:1382-1386
  4. Becker CG et al (1980) Induction of acute cholecystitis by activation of factor XII. J Exp Med 151(1):81-90
  5. Otto CM et al (1991) Factor XII and partial prekallikrein deficiencies in a dog with recurrent gastrointestinal hemorrhage. J Am Vet Med Assoc 198(1):129-131
  6. LIDA
  7. Randolph JF et al (1986) Factor XII deficiency and von Willebrand's disease in a family of miniature poodle dogs. Cornell Vet 76(1):3-10
  8. Peterson ME (2006) Brown spider envenomation. Clin Tech Small Anim Pract 21(4):191-193