Von Willebrand disease (VWD)
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Von Willebrand disease (VWD) is the most common inherited bleeding disorder*, caused by either a deficiency or dysfunction of von Willebrand factor (VWF). VWF is a large multimeric glycoprotein produced in endothelial cells and megakaryocytes. It plays a dual role in haemostasis:
Most VWD cases are inherited in an autosomal dominant manner, though severe type 3 disease is autosomal recessive. The clinical phenotype resembles a platelet disorder, with mucocutaneous bleeding such as epistaxis, menorrhagia, easy bruising, and prolonged bleeding after trauma or surgery. In contrast to haemophilia, haemarthroses and deep muscle haematomas are rare. The severity of bleeding varies widely and is often more pronounced in women due to gynaecological and obstetric challenges.
Types
Investigation
Management
*vWD is the most common inherited bleeding disorder overall, especially if mild/asymptomatic cases are included (affecting up to 1% of the population) however Haemophilia A is the most common of the severe bleeding disorders.
Types:
Clinical features: mucocutaneous bleeding (epistaxis, menorrhagia, bruising, post-surgical haemorrhage)
Key distinction: haemarthroses & muscle haematomas are rare (unlike haemophilia)
- Promotes platelet adhesion to damaged endothelium (particularly under high shear stress)
- Serves as a carrier protein for factor VIII (protecting it from premature degradation)
Most VWD cases are inherited in an autosomal dominant manner, though severe type 3 disease is autosomal recessive. The clinical phenotype resembles a platelet disorder, with mucocutaneous bleeding such as epistaxis, menorrhagia, easy bruising, and prolonged bleeding after trauma or surgery. In contrast to haemophilia, haemarthroses and deep muscle haematomas are rare. The severity of bleeding varies widely and is often more pronounced in women due to gynaecological and obstetric challenges.
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 3: total lack of vWF (autosomal recessive)
Investigation
- prolonged bleeding time
- APTT may be prolonged
- factor VIII levels may be moderately reduced
- defective platelet aggregation with ristocetin
Management
- tranexamic acid for mild bleeding
- desmopressin (DDAVP): raises levels of vWF by inducing release of vWF from Weibel-Palade bodies in endothelial cells
- factor VIII concentrate
*vWD is the most common inherited bleeding disorder overall, especially if mild/asymptomatic cases are included (affecting up to 1% of the population) however Haemophilia A is the most common of the severe bleeding disorders.
Key points summary:
- Most common inherited bleeding disorder
- Caused by ↓ levels or abnormal function of VWF
- VWF roles: platelet adhesion (esp. high shear), carrier for factor VIII
- Inheritance: usually autosomal dominant (type 3 = autosomal recessive)
Types:
- Type 1 = partial quantitative defect (≈80%)
- Type 2 = qualitative defect
- Type 3 = complete deficiency (rare, severe)
Clinical features: mucocutaneous bleeding (epistaxis, menorrhagia, bruising, post-surgical haemorrhage)
Key distinction: haemarthroses & muscle haematomas are rare (unlike haemophilia)