von-Willebrand Disease

Written by Dr Andrew Lam

Von-Willebrand Disease

Types of Von-Willebrand Disease

Type 1 – Characterised by reduced levels of VWF, and is associated with variable rates of bleeding (accounts for 75% of VWD) 

Type 2 – Caused by a dysfunction in the VWF protein, Many subtypes exist depending on the nature of the dysfunction that is identified

Type 3 – Absent or severely reduced VWF levels, associated with low Factor VIII levels. Associated with the most coagulopathic phenotype

Functions of VWF

1. In the presence of injury – forms a bridge between platelets and subendothelium in order to facilitate primary haemostasis
2. In response to shear stress, promotes platelet aggregation
3. Binds to Factor VIII in order to increase its half-life five fold by preventing its inactivation by Protein C and S

Investigations for Diagnosis

FBC – Often shows a normal platelet count, but in some patients may show a mild thrombocytopenia

Coags – APTT may be slightly prolonged if it has had a significant effect on Factor VIII due to its decreased half life

VWF Antigen – Allows for quantitative measurement of VWF 

Platelet Dependent VWF activity – Assays which assess the ability for VWF to bind to its usual partners and contribute to its function (i.e. Platelet Protein GP1b, Collagen and Factor VIII)

Factor VIII activity – May be reduced due to its decreased half life from a lack of VWF binding in the circulation