Factor XII deficiency in Cats (Felis) | Vetlexicon
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Factor XII deficiency

ISSN 2398-2950


Introduction

  • Factor XII is also known as Hageman factor.
  • Factor XII deficiency is the most common congenital coagulopathy recognized in the cat.
  • Cause: congenital deficiency of Factor XII.
  • Signs: asymptomatic unless combined with another disease process.
  • It has been reported in conjunction with other hemostatic abnormalities in which case there are clinical signs.
  • Diagnosis: it is suspected when activated partial thromboplastin time (APTT) is prolonged especially if the cat has no clinical hemostatic problem.
  • Treatment: none required.
  • Prognosis: excellent.

Presenting signs

  • Asymptomatic.

Special risks

  • Concurrent disorders or interventions that also decrease hemostasis, eg liver disease, drugs such as aspirin, concurrent coagulopathies.

Pathogenesis

Predisposing factors

General

  • An autosomal recessive disorder of domestic shorthairs and domestic longhairs.
  • Also reported in Siamese and Himalyan cats.
    Likely to be potentially identified in any breed.

Pathophysiology

  • An autosomal recessive genetic trait.
  • The exact defect is not known in cats. Factor XII is a zymogen that is converted into the active enzyme by proteolysis. This should happen when it is exposed to negatively charged surfaces such as collagen in the subendothelial matrix or antigen-antibody complexes. Activated factor XII is one element that can initiate the intrinsic pathway of coagulation.
  • Because the intrinsic pathway can be stimulated in other ways, eg by tissue factor, factor III or factor VII, factor XII seems not to be essentialin vivo. Indeed many species seem not to have factor XII.
  • Thus factor XII deficiency is asymptomatic despite prolongation of clotting timesin vitro.
  • Factor XII deficiency has also been detected in FIV positive cats Feline immunodeficiency virus. It is not clear whether this is coincidental or connected with the virus.

Epidemiology

  • Factor XII deficiency has been reported in combination with factor VIII:C deficiency (combined hemophilia A and Hageman factor deficiency). This is a condition that is expected to cause some bleeding problems after challenge from trauma or surgery. It has been reported in domestic shorthaired cats and results in a normal prothrombin time Hematology: prothrombin time and a prolonged activated partial thromboplastin time Hematology: activated partial thromboplastin time.
  • Combined hemophilia B and Hageman factor deficiency has also been reported in Siamese cats and domestic shorthaired cats. These cats have deficiencies of factor IX and XII and are expected to have quite serious bleeding tendencies after surgery or trauma. They will have a prolonged activated partial thromboplastin time.

Diagnosis

Presenting problems

  • Factor XII deficiency is suspected when all hematological and blood clotting tests are normal except for a prolonged activated partial thromboplastin time and activated clotting time (ACT).
  • Factor XII deficiency is most likely to be diagnosed when a cat has a suspected bleeding problem but in fact does not have a clinical problem, or when screening animals related to a known hemophiliac. It also may occur as a confusing laboratory test finding when a cat has an additional acquired or congenital disorder of hemostasis.
  • Other diseases with identical clotting profile findings that have been recorded in cats are hemophilia A (factor VIII:C deficiency) and hemophilia B (Christmas disease) (factor IX deficiency).
    The factor XII deficiency documented in these hemophiliac cats is completely coincidental, therefore the 'diseased' state is related to the factor VIII or IX defect, not the low factor XII.
  • Both these conditions have been recorded in domestic shorthaired cats and hemophilia B has also been seen in Siamese cats.

Diagnostic investigation

  • The clinical and laboratory findings to be expected in a cat with factor XII deficiency are: normal hematology (including platelet count Hematology: platelet count), normal buccal mucosal bleeding time Buccal mucosal bleeding time (as platelet number and function are normal), normal prothrombin time Hematology: prothrombin time (as the extrinsic path is normal).
  • Prolonged activated partial thromboplastin time (APTT)  Hematology: activated partial thromboplastin time.
  • Prolonged ACT Hematology: activated clotting time.
  • APTT corrections tests with normal plasma, absorbed plasma and normal aged serum will all correct the defect in test plasma, since factor XII is present in all three re-agents.
  • Specific factor XII assay can be performed using factor XII deficient substrate plasma and comparing test plasma with pooled normal feline plasma as the standard. Levels of Factor XII vary from 1-24%. Level of Factor XII is generally related to the prolongation of APTT.
  • All coagulation assays must be conducted with species specific re-agents, comparing test plasma with pooled normal plasma from the same species, even if human factor deficient plasma is used as the substrate.
    It is completely invalid to compare the samples with human coagulation factor standards.

Definitive diagnostic features

  • Laboratory tests.

Treatment

Initial symptomatic treatment

  • No treatment is necessary this is always an asymptomatic condition when present in isolation.

Monitoring

  • Not necessary.

Prevention

Outcomes

Prognosis

  • Excellent.

Reasons for treatment failure

  • Incorrect diagnosis.

Further Reading

Publications

Refereed papers

  • Recent references from PubMed and VetMedResource.
  • Brooks M & DeWilde L (2006) Feline Factor XII Deficiency. Comp Contin Educ Pract Vet 28 (2), 148-155 VetMedResource.
  • Hart S W & Nolte I (1994) Hemostatic disorders in Feline Immunodeficiency Virus-seropositive cats. J Vet Intern Med (5), 355-62 PubMed.
  • Littlewood J D & Evans R J (1990) A combined deficiency of factor VIII and contact activation defect in a family of cats. British Vet J 146 (1), 30-35 PubMed.
  • Dillon A R & Boudreaux M K (1988) Combined factors IX and XII deficiencies in a family of cats. JAVMA 193 (7), 833-4 PubMed.
  • Hoffman L, Sperling K, Dodds W J (1986) Acquired hemostatic problems in a cat with factor XII deficiency. Feline Practice 16 (1), 25-7 VetMedResource.

Other sources of information

  • Baldwin C J & Cowell (1997) Inherited Coagulopathies. In: Consultations in Feline Internal Medicine. 3rd edn. Ed: J R August. Philadelphia: W B Saunders. pp 488.