von Willebrand Disease (VWD)
A rare inherited bleeding disorder caused by quantitative or qualitative defects of von Willebrand factor (VWF), a protein essential for platelet adhesion and for protecting Factor 8 (FVIII) from degradation. Reduced or dysfunctional VWF impairs platelet adhesion and may lower FVIII levels, resulting in bleeding of variable severity, either spontaneously or in association with trauma or invasive procedures. Three main types are recognised according to the nature of the von Willebrand factor defect: partial quantitative deficiency (type 1), qualitative defects (type 2), and virtually complete deficiency (type 3).
The estimated prevalence of VWD in the general population is approximately 1% when laboratory abnormalities are included. However, clinically significant VWD requiring medical attention is much less common, affecting around 1 in 10,000 individuals. Type 3 VWD, the most severe form, is rare, with an estimated prevalence of approximately 1 in 1,000,000.
Clinical description
The age at diagnosis varies and more severe forms usually present earlier in life. VWD causes bleeding of variable severity, either spontaneously or after trauma or invasive procedures. Bleeding is typically mucocutaneous, such as epistaxis, heavy menstrual bleeding, easy bruising, and prolonged bleeding from minor injuries. In severe cases, major bleedings including haematomas and hemarthrosis may occur.
Etiology
VWD is caused by mutations in the VWF gene located on chromosome 12p13.3, which encodes von Willebrand factor, a large multimeric glycoprotein. VWF is synthesised by endothelial cells and megakaryocytes and is present in plasma, platelets, and endothelial storage granules. It plays a crucial role in mediating platelet adhesion to the injured vessel wall and serves as a carrier protein for factor VIII (FVIII), protecting it from premature degradation.
Diagnostic methods
Diagnosis of VWD is based on laboratory assessment of von Willebrand factor quantity and function, together with measurement of FVIII activity. Initial evaluation typically includes VWF antigen (VWF:Ag), VWF activity assays, and FVIII activity. Determination of the specific VWD type requires additional specialised tests, such as analysis of VWF multimer distribution and, in selected cases, genetic testing.
Differential diagnosis
Standard laboratory tests usually help distinguish VWD from haemophilia A. However, certain subtypes, such as type 2N, require additional specialised testing. It may also be difficult to differentiate inherited VWD from acquired forms that develop later in life due to other medical conditions. Furthermore, people with blood group O naturally have lower VWF levels, which should be considered when interpreting results.
Antenatal diagnosis
In at-risk pregnancies, identification of pathogenic VWF gene variants in the family may allow prenatal diagnosis, particularly in cases of type 3 VWD or severe forms with a known genetic mutation.
How is VWD inherited?
Von Willebrand Disease is usually inherited. It is caused by changes in the VWF gene and can affect both males and females. In most cases, a child inherits the condition from one or both parents.
Types 1 and 2 VWD are usually inherited in an autosomal dominant pattern. This means that a parent with VWD has a 50% chance of passing the condition on to each child.
Type 3 VWD is typically inherited in an autosomal recessive pattern. This occurs when a child inherits a defective gene from both parents. In such cases, parents may have mild symptoms or no symptoms at all, while the child may have a more severe form of the disease.
In rare cases, VWD may arise from a new (spontaneous) genetic change.
Genetic counseling
VWD is most commonly inherited in an autosomal dominant pattern. However, type 3 VWD and certain type 2 subtypes are inherited in an autosomal recessive manner.
Genetic counselling is recommended to help individuals and families understand the pattern of inheritance, the potential severity of the condition, and the risk of transmission to offspring. It also provides an opportunity to identify and screen other potentially affected family members.
For couples at risk of having a child with type 3 VWD, counselling in a specialised multidisciplinary centre may be particularly appropriate.
Type 1
Prevalence:
1 / 10,000
Inheritance:
Autosomal dominant
Age of onset:
All ages
Bleedings:
None-Severe
Type 2
Prevalence:
1-9 / 1,000,000
Inheritance:
Autosomal dominant (common), Autosomal recessive (uncommon)
Age of onset:
All ages
Bleedings:
Moderate-Severe
Type 3
Prevalence:
1/ 1,000,000
Inheritance:
Autosomal recessive
Age of onset:
Infancy, Neonatal
Bleedings:
Severe
Management and treatment
Treatment of von Willebrand Disease depends on the type of the condition and the severity of bleeding. In many people with type 1 VWD, desmopressin (DDAVP) is an effective treatment. This medication works by stimulating the release of stored von Willebrand factor into the bloodstream and can be used to prevent or control bleeding in appropriate situations. In type 2 VWD, the response to desmopressin varies depending on the subtype. Some patients may benefit from it, while others require treatment with VWF replacement therapy. In type 3 VWD, desmopressin is not effective because the body does not produce sufficient VWF. These patients require replacement therapy with VWF concentrates. In some situations, particularly at the start of treatment or before surgery, factor VIII (FVIII) may also need to be administered together with VWF.
Several innovative therapies are currently under clinical investigation for von Willebrand Disease. These include monoclonal antibodies targeting protein S or von Willebrand factor, PEGylated aptamers designed to modulate VWF function, bispecific nanobodies that prolong VWF half-life, and other novel hemostatic strategies. While some of these therapies are in advanced clinical trials, others remain in early development. Participation in clinical trials may be an option for selected patients and should be discussed with specialised treatment centres.
Prognosis
With appropriate care and follow-up in specialised centres, the outlook for people with von Willebrand Disease is generally favourable. Even individuals with more severe forms of the condition can achieve good bleeding control and maintain a good quality of life with tailored treatment and regular monitoring.
Futher Information and Resources
Last updated on 16 February 2026
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