von Willebrand disease - Clotting disorders

von Willebrand disease

Definition

An inherited coagulation disorder resulting in platelet dysfunction and low levels of circulating factor VIII.

Aetiology/pathophysiology

von Willebrand factor (vWF) is a glycoprotein that has two functions in haemostasis. vWF acts as a bridging molecule between allowing platelet aggregation and adhesion to damaged endothelium. vWF acts as a carrier protein for circulating factor VIII increasing the half-life of factor VIII five-fold.

Type 1 (autosomal dominant) is the most common type. It causes are reduction in the amount of vWF.

Type 2 (usually an autosomal dominant) causes functional abnormalities of vWF. There are at least four subtypes.

Type 3 (autosomal recessive) causes extremely reduced or undetectable levels of vWF.

Clinical features

Type 1 and 2 causes mild disease with bleeding following injury, menorrhagia and epistaxis. Type 3 causes spontaneous bleeding from early life.

Investigations

Activated partial thromboplastin and prothrombin times are raised, but correctable with 50% normal serum other coagulation measures are normal.

Factor VIII:vWF and VIII:c assays are low.

Management

Treatment of bleeding and prophylaxis in severe disease uses intermediate purity factor VIII concentrates or VIII:vWF concentrates. 1-desamino-8-D-arginine vasopressin (DDAVP) releases factor VIII from endothelial cells and is of value in mild to moderate disease.