Von Willebrand's syndrome in Horses (Equis) | Vetlexicon
equis - Articles

Von Willebrand's syndrome

ISSN 2398-2977


Introduction

  • Cause: presumed inherited disorder causing impaired primary hemostasis, but evidence for inherited nature is tenuous at best but deficiency is recorded very rarely in Thoroughbred and Quarterhorses.  Other breeds have also been implicated but there are far too few cases to establish any convincing heritability.
  • Alteration in the structure, function or concentration of von Willebrand factor (vWF)   Von Willebrand's factor   which is found in platelets, vascular endothelium and in plasma as a free glycoprotein.
  • Results in decreased platelet aggregation and adhesion at sites of hemorrhage or vascular endothelial collagen exposure.
  • Acquired forms may exist; transient deficiencies have been detected following treadmill exercise.
  • Signs: varying degrees of hemorrhage, from sub-clinical to life-threatening/sudden death.
  • Diagnosis: plasma vWF concentrations.
  • Treatment: temporary response follows administration of platelet rich plasma.  May need whole blood transfusions. 
  • Prognosis: incurable, risk of life-threatening hemorrhage from minor trauma or even normal behavior, eg hemarthrosis.

Presenting signs

  • Defective primary hemostasis. 
  • Excessive or prolonged bleeding following even minor trauma or surgery.
  • Rarely any evidence of capillary bleeding (petechiation).
  • Subcutaneous hematomas.
  • Possibility of milder forms of the disease with milder signs that might easily be overlooked. Concurrent clotting deficits, eg DIC/FDP/warfarin therapy/poisoning, or liver failure could mask the disease.

Acute presentation

  • Neonatal death possibly with persistent or heavy cord hemorrhage (note Factor VIII deficiency can occur concurrently the two proteins are closely related).
  • Useful to check clotting in the placental vessels failure to clot is a strong indicator of a hemophiliac disorder (of which this is one type).
  • Post-surgical/traumatic hemorrhage.

Geographic incidence

  • Worldwide.

Age predisposition

  • Cases have been reported in both foals and adults.

Breed/Species predisposition

Cost considerations

  • Cost of therapy.

Special risks

  • Surgery or trauma may   →    hemorrhage.

Pathogenesis

Etiology

  • vWF is a glycoprotein contained in vascular endothelia cells and thrombocytes. 
  • The factor facilitates platelet aggregation and adhesion to exposed vascular sub-endothelium. 
  • Partial or absolute deficiency of vWF therefore results in widespread hemorrhagic diathesis.  Individual sites subjected to trauma may be the first indicator of a problem.

Specific

  • Treatment with NSAIDs, or anticoagulants such as warfarin may exacerbate the problem but these would not normally be used in young foals anyway.
  • Liver disease   Liver disease: overview  .

Pathophysiology

  • Genetic deficiency.
  • Three forms are recognized in other species:
    • Type 1: an autosomal incompletely dominant gene with variable expression. Heterozygote and homozygote animals can show variable degrees of hemorrhagic diathesis. 
    • Type 2: rarest form in which there is a decrease in the of the larger vWF molecules.
    • Type 3: rare autosomal recessive gene form often combined with a profound factor VIII deficiency.
  • Acquired forms may relate to microvascular damage and consumptive coagulopathy, eg following treadmill exercise.

Timecourse

  • Acute in severe cases. 
  • A few cases have been identified in older horses suggesting either that there is an acquired form (possibly associated with liver failure) or that there are milder forms of the condition that may be exacerbated by concurrent hemorrhagic disorders. In mild cases may remain sub-clinical for many years.

Epidemiology

  • Too few cases have been reported to determine the epidemiology of the condition.

Diagnosis

Presenting problems

  • Excessive or prolonged bleeding.
  • Hemorrhage at unexpected sites such as multiple joints, peritoneal and pleural cavities and intra-ocular bleeding.

Client history

  • Epistaxis or hemorrhage into bowel or urine in a young foal is suggestive of clotting disorders. 
  • Lethargy.
  • Unexplained joint swelling and lameness.
  • Subcutaneous soft tissue swellings.

Clinical signs

  • Lethargy/anemia.
  • Tachypnea.
  • Hemorrhage:
    • Oral mucosa.
    • Epistaxis.
    • Urinary tract hemorrhage.
    • Gastrointestinal hemorrhage.
    • Subcutaneous.
  • Fever.
  • Obvious petechiae rare.
  • Hemorrhage into body cavities or into joints is more typical of coagulation factor deficiencies but the close relationship with Factor VIII in equine cases means that complex clotting deficits are probably more common than a single factor problem.

Diagnostic investigation

Hematology
  • Hemorrhage may result in anemia especially if prolonged or severe. 
  • Regenerative anemia may be detected.
  • Platelet count shows adequate numbers.
Other 
  • In vivo bleeding time - usually prolonged.
  • Activated clotting time (ACT) - usually normal. 
  • Activated partial thromboplastin time (APTT) - usually normal. 
  • Prothrombin time (PT) - usually normal. 
  • Normal results (ACT/APTT/PT) indicate intact coagulation.
  • Fibrinogen and Serum Amyloid A (SAA) concentrations are normal or may be independently affected by concurrent disease.
  • Where vWF is the sole abnormality, the Factor VIII concentration is normal.

Confirmation of diagnosis

Discriminatory diagnostic features

  • Prolonged buccal mucosal bleeding time with normal platelet numbers and no clinical signs associated with vasculitis, eg petechiae, non-thrombocytopenic purpura, ecchymoses.

Definitive diagnostic features

  • Measurement of plasma concentrations of vWF, low levels confirm von Willebrand's syndrome. The Animal Diagnostic Centre, Cornell University, USA have a validated equine vWF ELISA assay.

Gross autopsy findings

  • Evidence of clotting disorder, eg hematomas, hemarthrosis, petechial hemorrhages.

Histopathology findings

  • Evidence of hemorrhage.

Differential diagnosis

  • Inherited coagulopathies, eg Factor VIII hemophilia (may be concurrent).
  • Liver failure. 
  • Acquired coagulopathies, eg warfarin poisoning (accidental and iatrogenic use of warfarin for therapy).
  • Thrombocytopenia   Thrombocytopenia: overview  (consumptive as in DIC and SIRS) or immune-mediated.
  • Bone marrow suppression/obliteration (non-generative thrombocytopenic purpura/neoplasia such as lymphosarcoma).
  • Hereditary platelet defects.
  • Acquired platelet dysfunction, eg secondary to NSAIDs.

Treatment

Initial symptomatic treatment

  • Fresh platelet rich plasma is preferred or fresh-frozen plasma. 
  • Cryoprecipitate concentrated plasma product containing high concentrations of factor VIII and vWF is available for human and canine patients but the value of these in horses is not established and in any case the treatment is unwarranted.
  • If the animal is profoundly anemic then fully cross matched whole blood transfusion is indicated.

Standard treatment

  • As for initial symptomatic treatment.

Monitoring

  • Clinical signs.
  • Plasma vWF concentrations.

Subsequent management

Treatment

  • No effective long-term treatment is available. 
  • Individual cases may benefit from platelet rich plasma transfusion but this lasts only for days and then the problem is just as severe.
  • There are however, some animals that are diagnosed with the condition later in life so it is possible that there may be degrees of deficiency and some acquired cases - one reported case.
  • Concurrent Factor VIII deficiency (inherited hemophilia) may be a complicating factor that precipitates severe signs.
  • Each individual crisis requires treatment as long as the case is not a welfare issue.

Monitoring

  • Clinical signs.
  • Plasma vWF concentrations.

Prevention

Control

  • The heritability is not established in spite of a single recorded case involving a Thoroughbred mare and her foal. 
  • It is probably wise to use a different stallion at a subsequent covering if a foal is found to be affected.
  • In theory the parents of affected foals could justifiably be removed from future breeding but the heritability is uncertain.

Prophylaxis

  • Although the condition can be temporarily resolved by administration of plasma or preferably fresh platelet-rich plasma the long-term outlook is hopeless.

Group eradication

  • Do not use the same combination of mare and stallion again after an effected foal has been identified.

Outcomes

Prognosis

  • Incurable.
  • Some individuals can survive and thrive but there is a persistent risk of hemorrhage into any organ that is traumatized at all and hematoma formation.

Expected response to treatment

  • Short-term response to appropriate therapy.

Reasons for treatment failure

  • Incurable condition.

Further Reading

Publications

Refereed papers

  • Recent references from PubMed and VetMedResource.
  • Laan T T J M, Goehring L S & Sloet van Oldruitenborgh-Oosterbaan M M (2005) Von Willebrand disease in an eight-day-old quarterhorse foal. Vet Rec 157 (11), 322-324 PubMed.
  • Rathgeber R A et al (2001) Von Willebrand Disease in a Thoroughbred mare and foal. J Vet Intern Med 15, 63-65 PubMed.
  • Smith J M, Meyers K M, Barbee D D, Schott H & Bayly W M (1997) Plasma von Willebrand factor in Thoroughbreds in response to high intensity treadmill exercise. Am J Vet Res 58, 71-76 PubMed.
  • Benson R E, Catalfamo J L & Dodds W J (1992) A multispecies enzyme linked immunosorbent assay for von Willebrands factor. J Lab Clin Med 19 (4), 420-427 PubMed.
  • Brooks M, Leith G S, Allen A K et al (1991)Bleeding disorder (von Willebrand Disease) in a Quarterhorse. JAVMA 198, 114-115 PubMed.

Other sources of information

  • Brooks M (2000) von Willebrands Disease. In: Veterinary Haematology. 5th edn. Eds: Schalm O S, Feldman B F, Zinkl J G & Jain N C. Lippincott, Williams & Wilkins, USA. pp 509-515.