Von Willebrand's disease

Von Willebrand's disease is the most common inherited bleeding disorder. The majority of cases are inherited in an autosomal dominant fashion* and characteristically behaves like a platelet disorder i.e. epistaxis and menorrhagia are common whilst haemoarthroses and muscle haematomas are rare.

Role of von Willebrand factor

• large glycoprotein which forms massive multimers up to 1,000,000 Da in size
• promotes platelet adhesion to damaged endothelium
• carrier molecule for factor VIII

Types

• type 1: partial reduction in vWF (80% of patients)

• type 2*: abnormal form of vWF

  • type 2A VWD is caused by defective platelet adhesion due to decreased high molecular weight VWF multimers (i.e. the VWF protein is too small).
  • Type 2B is characterised by a pathological increase of VWF-platelet interaction.
  • Type 2M is caused by a decrease in VWF-platelet interaction (not related to loss of high molecular weight multimers).
  • Type 2N is caused by abnormal binding of the VWF to Factor VIII. There is no clear correlation between symptomatic presentation and type of VWD however common themes amongst patients include excessive mucocutaneous bleeding, bruising in the absence of trauma and menorrhagia in females.

• type 3**: total lack of vWF (autosomal recessive)

• chromosome 12, autosomal dominant (but more common in females)

• Bleeding related to platelets (epistaxis, gingival, gums) with a normal platelet count;

• exacerbated by the use of aspirin

• it is a protective carrier for factor VIII; hence factor VIII may be low and hence aPTT may be elevated (50%)

Dx -

• low vWF (antigen) level;
• Ristocetin cofactor assay (or vWF activity) - detects vWF dysfunction; deficient ristocetin-induced platelet aggregation
  • it means there is no response to ristocetin but this is corrected with the addition of normal plasma (mixing study)
• low factor VIIIc
• prolonged BT with normal platelet count