von Willebrand disease

Keywords: VWD

Key Information

Appropriate Tests

 

The diagnosis is usually considered because of a personal and/or family history of easy bruising or bleeding. Normal results on initial testing (Full blood count, APTT) do not exclude VWD.

The diagnosis is established on the basis of assays of Factor VIII, von Willebrand factor Ag, Collagen binding assay, Ristocetin cofactor and possibly other assays. See von Willebrand disease testing.

Levels of factor VIII and VWF increase with exercise, stress and endogenous or exogenous oestrogen.

In females, blood should be collected during menstruation, normal results mid-cycle or during pregnancy do not exclude the diagnosis.

Studies should be repeated on 2-4 occasions if clinical suspicion is high or if a previous diagnosis of VWD is to be refuted.

von Willebrand disease type 1

Quantitative deficiency of VWF (functional and antigen assays). Concordant reduction in VWF antigen and ristocetin cofactor activity. Most respond to DDAVP.

von Willebrand disease type 2

Von Willebrand factor is qualitatively abnormal as demonstrated by an abnormally low VWF activity to antigen ratio (types 2A, 2B and 2M), VWF multimer patterns, RIPA, or by other assays such as quantitative assay of patients’ VWF binding for factor VIII (type 2N)

Type 2N (Normandy) variant is characterised by mutations in VWF affecting the binding site for factor VIII and may provide an alternative diagnosis to haemophilia A.

Type 2B variants develop thrombocytopenia with desmopressin and this should be avoided.

See von Willebrand disease testing.

von Willebrand disease type 3

Rare and is associated with a severe deficiency of VWF.

Pseudo von Willebrand disease

A disorder of platelets, characterised by increased affinity for VWF.

There is a risk of increasing thrombocytopenia with either desmopressin or cryoprecipitate/factor VIII infusion, which should be avoided.

Acquired von Willebrand disease especially

  • Lymphoma (non-Hodgkin)
  • Plasma cell myeloma
  • Myeloproliferative neoplasms (especially with high platelet counts) 
  • Hypothyroidism
  • Wilms' tumour

Variable reduction in Factor VIII, von Willebrand factor Ag, VWF (functional) assays. Characterised by structural or functional defects of VWF. There may be reduced synthesis of von Willebrand disease, or increased clearance of VWF from the circulation.