Von Willebrand Disease (vWD) is caused by qualitative and quantitative deficiencies in von Willebrand factor. It is characterised by mucocutaneous haemorrhage.
Subtypes of von Willebrand Disease
Subtype
Description
Type 1 von Willebrand disease (75%)
Autosomal dominant quantitative defect of vWF. May have low levels of factor VII. Presents with mild to moderate bleeding following haemoastatic challenge (e.g., surgery and dental procedures), and menorrhagia in women.
Type 2 von Willebrand disease (20%)
Qualitative defect of vWF. Type 2A is the most common form. Type 2B has a shortage of both vWF and platelets.
Type 3 von Willebrand disease (1 – 5%)
Autosomal recessive inheritance with virtually complete deficiency of vWF. It may present with more serious bleeding, e.g. haemarthrosis and gastrointestinal bleeding.
Acquired von Willebrand syndrome
Due to underlying conditions that affect the function of vWF, e.g., lymphoproliferative and myeloproliferative diseases, malignancy, and autoimmune conditions
Sites of synthesis of vWF
Cytoplasmic Weibel-Palade bodies of endothelial cells
Alpha granules of platelets
Functions of vWF
Platelet adhesion
Platelet aggregation
Carries factor VIII in its inactive form, preventing it from being degraded
Pathophysiology
Release of vWF in response to haemostatic
Qualitative and quantitative defect of vwf → decreased binding of platelet Gp1B/IX/X and GpIIa/IIIa at shear stress → platelet-type bleeding
Qualitative and quantitative defects of vWF → rapid proteolysis of factor VIII → impaired complex with IXa and activation of Xa in the intrinsic factor → coagulpathy
