Von Willebrand's disease

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Nail bed bleeding time, a common test to detect prolonged clotting in Von Willebrand patients[1]

Von Willebrand's disease (VWD) is an autosomal recessive congenital hemophilia characterized by a clotting defect and platelet dysfunction.

Von Willebrand's in dogs results from a lack of functional von Willebrand factor (vWF), a glycoprotein that is involved in platelet adhesion to the vessel wall during formation of the primary hemostatic plug. This leads to abnormal primary hemostasis (platelet plug formation) and prolongation of bleeding time. The release of vWF is stimulated by an assortment of other substances such as histamine, fibrin, estrogen, collagen, platelet-activating factor, thrombin, and adenosine diphosphate[2]. In areas with a high blood flow rate, vWF is necessary for the platelets to adhere to the subendothelium. Platelets subsequently bind to vWF and adhere to the vessel wall.

Von Willebrand's disease is primarily reported in Corgi, Doberman, German shepherd, German Short-Haired Pointer, Golden Retriever, Shetland Sheepdog and Standard Poodle breeds[3].

Clinically, this disease is categorized, based on clinical symptoms, from Type 1 (mild) through to type 3 (severe).

Affected dogs usually present with buccal bleeding, commonly observed in dogs after chewing bones or after removal of deciduous teeth. Incidental signs are comonly observed following routine desexing, with increased bleeding intra-operatively or post-operatively[4]. Other signs include hematemesis and bloody diarrhea.

An abnormal presentation has been reported in the Doberman where increased microvascular bleeding within muscle may lead to heterotopic osteochondrofibrosis, characterized by multiple intramuscular masses composed of osseous, chondrous or fibrous tissue in or around the muscles of the hip[5].

Diagnosis is readily established by ELISA or PCR determination of Von Willebrand factors from blood samples[6]. Routine coagulation screening tests usually show the clotting times as normal.

The classification of VWD is used to recommend therapeutic protocols:

A differential diagnosis would include other causes of bleeding such as hemophilia, thrombopathia, aplastic pancytopenia, hemangiosarcoma and Waldenström's macroglobulinemia.

Emergency treatment of bleeding episodes is accomplished by whole blood transfusion. Long term maintenance of affected dogs involves use of Vit-K oral supplementation.

Vasopressin is an alternative treatment for vWD-associated bleeding episodes, given at 1 µg/kg SQ; however, Type I vWD responds poorly to long-term vasopressin therapy[9].

Drugs with antiplatelet or anticoagulant effects should be avoided, including nonsteroidal anti-inflammatory drugs, estrogens, cytotoxic medications, heparin, coumadin, plasma expanders and sulfonamide antibiotics.

References

  1. Cornell Uni
  2. Thomas JS (1996) Von Willebrand's disease in the dog and cat. Vet Clin N Am Small Anim Pract 26:1089-1107
  3. Harvey JW, Meyer DJ (1998) Veterinary Laboratory Medicine: Interpretation and Diagnosis.W. B. Saunders Co., Philadelphia, pp.131
  4. Brooks M (2000) von Willebrand Disease. In: Feldman BF, Zinkl JG, Jain NC: Schalm's Veterinary Hematology, 5th ed. Lippincott, Williams and Wilkins, pp:509-515
  5. Dueland RT et al (1990) von Willebrand heterotopic osteochondrofibrosis in Doberman pinschers: five cases (1980-1987). J Am Vet Med Assoc 197(3):383-388
  6. Kramer JW et al (2004) A von Willebrand's factor genomic nucleotide variant and polymerase chain reaction diagnostic test associated with inheritable type-2 von Willebrand's disease in a line of german shorthaired pointer dogs. Vet Pathol 41(3):221-228
  7. Johnstone IB (1988) Clinical and laboratory diagnosis of bleeding disorders. Vet Clin N Am Small Anim Pract 18:21-33
  8. Pathak EJ (2004) Type 3 von Willebrand's disease in a Shetland sheepdog. Can Vet J 45(8):685-687
  9. Johnstone IB (1999) Desmopressin enhances the binding of plasma von Willebrand factor to collagen in plasmas from normal dogs and dogs with type I von Willebrand's disease. Can Vet J 40(9):645-648