Von Willebrand Disease

Question 8.2 from the first paper of 2013 presents the candidates with a coagulopathy scenario where the patient has a normal APTT but an abnormally prolonged bleeding time. Because Factor 8 relies on vWF activity, and in the absence of vWF one is effectively Factor 8-deficient, the APTT may be slightly prolonged. The PT would be normal. An excellent 2013 article by Castaman et al has been pillaged for the details that make up this summary.

Pathophysiology

  • Most common inherited bleeding disorder (autosomal dominant)
  • Prevalence is about 1–2%
  • Only one in every ten cases have clinically relevant disease
  • Caused by the deficiency or abnormality of VWF.
  • VWF is required for platelet adhesion to the subendothelium
  • VWF also serves as carrier of Factor VIII, protecting it from Protein C mediated inactivation (hence in VWD Factor VIII levels are low, or effectively low).

There are three main types of VWD:

  • Type 1: incomplete absence of VWF; mild symptoms (most common)
  • Type 2: presence of dysfunctional VWF; mild symptoms
  • Type 3: virtually complete absence of VWF; severe symptoms. 

Investigations of suspected Von Willebrand disease

History and examination

  • Beyond looking for ecchymoses and acute bleeding, the examination has nothing specific to offer.
  • Similarly, "history of bleeding" is very nonspecific. Many people may complain of excessive bleeding, and most would not have VWF. History is unreliable, and the use of standardised bleeding history questionnaires is recommended to compute some sort of objective "bleeding risk". People with a high bleeding risk should go on to be tested biochemically.
  • Severity of bleeding usually correlates with Factor VIII level.
  • Type 1 usually has epistaxis and mucosal haemorrhages, bleeding after dental work, etc
  • Type 3 may have haemarthrosis and deep haematomas similar to haemophilia.

Blood biochemistry

  • Von Willebrand Factor level
  • Factor VIII level
  • Ristocetin co-factor activity (VWF:RCo)
  • von Willebrand factor collagen binding (VWF:CB)

VWF level and FVIII level are the tests which correlate with severity of disease; the other two tests discriminate between different subtypes of Type 2 VWD.

Management

  • DDAVP increases VWF and FVIII plasma concentrations  by provoking release of stored VWF.
  • Replacement therapy may be available, where the patient regularly receives concentrated VWF and Factor VIII.
  • In an acutely bleeding patient, platelet transfusion and tranexamic acid are indicated.

References

Budde, Ulrich, et al. "Laboratory diagnosis of congenital von Willebrand disease."Seminars in thrombosis and hemostasis. Vol. 28. No. 02. Copyright© 2002 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.:+ 1 (212) 584-4662, 2002.

Kamal, Arif H., Ayalew Tefferi, and Rajiv K. Pruthi. "How to interpret and pursue an abnormal prothrombin time, activated partial thromboplastin time, and bleeding time in adults." Mayo Clinic Proceedings. Vol. 82. No. 7. Elsevier, 2007.

Castaman, Giancarlo, Anne Goodeve, and Jeroen Eikenboom. "Principles of care for the diagnosis and treatment of von Willebrand disease." Haematologica 98.5 (2013): 667-674.