On this page
Von Willebrand disease
Also known as Von Willebrand disease type 1 · Von Willebrand disease type 2 · Von Willebrand disease type 3 · vWD
VWD is the most frequently encountered inherited bleeding condition, impacting approximately 1% of the population in varying degrees. It leads to increased bruising and bleeding, and symptoms can range from mild to severe, affecting daily life.
Overview
Von Willebrand disease (VWD) is the most common inherited bleeding disorder, affecting how the blood clots. It is caused by issues with a protein called von Willebrand factor (VWF), which plays a crucial role in the clotting process. VWF helps platelets (small blood cells that stop bleeding) stick together and to the walls of damaged blood vessels. It also carries another clotting protein, Factor VIII, protecting it from being broken down too quickly [PMID:33677180]. When VWF is either insufficient or does not work correctly, blood clotting can be impaired, leading to prolonged bleeding.
VWD is classified into different types. Type 1 is the most common, characterised by lower-than-normal levels of VWF. Type 2 involves VWF that is present but does not function properly, and this type has several sub-types (2A, 2B, 2M, 2N). Type 3 is the rarest and most severe form, where there is very little or no VWF, leading to significant bleeding problems. The severity of VWD symptoms can vary widely, even within the same family, from mild bruising to severe, life-threatening haemorrhages [PMID:33677180].
Around 1% of the general population may have VWD, making it a relatively common genetic condition. However, many individuals with mild forms may not be aware they have it until a specific event, such as surgery or significant injury, triggers symptoms [PMID:27083818].
Symptoms & clinical features
The symptoms of Von Willebrand disease are primarily related to prolonged or excessive bleeding. These can range in severity depending on the type and specific characteristics of the VWF deficiency or dysfunction. Common symptoms include easy bruising, frequent or prolonged nosebleeds (epistaxis), and heavy or extended menstrual bleeding (menorrhagia) in women [PMID:33677180].
Other symptoms may include bleeding from the gums, particularly after brushing teeth, or prolonged bleeding after minor cuts or dental procedures. After surgery or an injury, individuals with VWD might experience excessive or delayed bleeding. In more severe forms, such as Type 3 VWD, there can be spontaneous bleeding into joints or muscles, which can be painful and lead to long-term joint damage if not managed appropriately.
Video: Genetics 101
Affected organs
VWD primarily affects the blood and blood vessels throughout the body, as its core issue lies with the blood clotting process. Therefore, symptoms can manifest in any organ system where bleeding might occur. Commonly affected areas include the skin (leading to easy bruising), the mucous membranes (resulting in nosebleeds, gum bleeding, and heavy menstrual bleeding), and the gastrointestinal tract, though GI bleeding is less common but can be serious.
In severe cases, particularly with Type 3 VWD, bleeding can occur into joints (haemarthrosis) or muscles, which can cause pain and damage over time. Additionally, women with VWD may experience significant bleeding during childbirth or after gynaecological procedures, highlighting the impact on the reproductive system.
Risks & severity
The severity of Von Willebrand disease varies considerably. Type 1 VWD often presents with mild to moderate bleeding symptoms, and some individuals may only be diagnosed after a significant bleeding event, such as surgery or trauma. Type 2 VWD encompasses several subtypes with varying effects on VWF function, leading to a range of bleeding symptoms that can be mild, moderate, or occasionally severe. Type 3 VWD is the most severe form, characterised by very low or undetectable levels of VWF, leading to frequent and serious bleeding episodes, often from an early age, including spontaneous bleeding into joints and muscles.
The lifetime risk of bleeding is increased for individuals with VWD compared to the general population. The age of onset for symptoms also varies; some individuals with more severe forms may experience symptoms in childhood, while those with milder VWD might not develop noticeable issues until adulthood. For women, heavy menstrual bleeding can be a significant issue and a common reason for diagnosis [PMID:33677180]. Complications from severe bleeding, if not managed, can include anaemia, joint damage from recurrent bleeds, and in rare cases, life-threatening haemorrhage.
Genetic causes
Von Willebrand disease is caused by pathogenic variants in the VWF gene, which provides instructions for making the von Willebrand factor protein. This protein is crucial for normal blood clotting. It has two main roles: helping platelets stick to damaged blood vessel walls (platelet adhesion) and carrying and protecting another clotting protein, Factor VIII, from degradation [PMID:27083818].
Pathogenic changes in the VWF gene can lead to either a reduced amount of functional VWF (as seen in Type 1 and Type 3 VWD) or VWF that is present in normal amounts but does not work correctly (as seen in Type 2 VWD). Different types of genetic changes, such as deletions, insertions, or point variants, can affect the VWF protein in various ways, leading to the different VWD types and their associated symptoms. Genetic testing of the VWF gene can help confirm a diagnosis and determine the specific type of VWD, which can influence treatment choices.
- VWF von Willebrand factor
Inheritance pattern
Von Willebrand disease typically follows an autosomal dominant inheritance pattern. This means that a person only needs to inherit one copy of the altered VWF gene from either parent to develop the condition. If a parent has VWD, there is a 50% chance with each pregnancy that their child will also inherit the condition [PMID:33677180].
Autosomal dominant inheritance patterns mean that both males and females are equally likely to be affected. However, the severity of symptoms can vary significantly, even among family members who have inherited the same genetic change. In rare, severe cases of Type 3 VWD, the condition can be inherited in an autosomal recessive manner, meaning a child must inherit two altered copies of the VWF gene (one from each parent) to be affected. In such cases, the parents are typically carriers and may not show symptoms themselves or have very mild VWD.
Each child has a 50% chance of inheriting the pathogenic variant, regardless of sex.
Subtypes & variants
This page covers Von Willebrand disease as a single condition. Several distinct variants and clinical subtypes are recognised in the literature - they share the underlying biology and broad management approach, but differ in severity, age of onset, or causative gene:
- Type 1 (quantitative - partial) OMIM 193400
Most common form (~75% of vWD). Partial deficiency of normally functioning von Willebrand factor. Mild to moderate mucocutaneous bleeding. Often responsive to desmopressin.
- Type 2 (qualitative) OMIM 613554
Functional defect with structurally abnormal von Willebrand factor. Subtypes 2A, 2B, 2M, and 2N differ in mechanism and treatment response. Genetic and laboratory subtyping guides management.
- Type 3 (quantitative - severe) OMIM 277480
Rare and severe form with virtually absent von Willebrand factor. Joint and soft-tissue bleeding similar to haemophilia, plus severe mucocutaneous bleeding. Recombinant or plasma-derived vWF concentrate is the mainstay.
Diagnosis & testing
Diagnosing Von Willebrand disease usually begins with a thorough medical history, focusing on personal and family bleeding tendencies. This is followed by a series of blood tests. Initial screening tests may include a full blood count, prothrombin time (PT), and activated partial thromboplastin time (aPTT), although these can often be normal in VWD.
Specific diagnostic tests for VWD measure the amount of VWF in the blood (VWF antigen), how well it functions (VWF activity assays, such as VWF:RCo or VWF:GPIbM), and the amount of Factor VIII. If these tests suggest VWD, further specialised tests may be done to determine the specific type of VWD, which is crucial for appropriate management. Genetic testing of the VWF gene (NHS R-code: R355) can confirm the diagnosis, classify the type of VWD, and help identify at-risk family members. Patients are typically referred to a haematologist for assessment and diagnosis, often via clinical genetics services within the NHS.
Management & lifestyle
Management of Von Willebrand disease is tailored to the specific type and severity of the condition, as well as the individual's bleeding history. The primary goal is to prevent and control bleeding episodes. For individuals with mild VWD (often Type 1), treatment may only be needed before surgery, dental procedures, or during bleeding episodes. Desmopressin (DDAVP) is often used for mild VWD, as it helps release stored VWF and Factor VIII from the body's cells into the bloodstream.
For more severe forms of VWD or when desmopressin is not effective, treatment may involve VWF-containing factor concentrates, which replace the missing or dysfunctional VWF. Antifibrinolytic agents, such as tranexamic acid, can also be used to stabilise blood clots and reduce bleeding, particularly for nosebleeds or heavy menstrual bleeding. Women with VWD may be offered hormonal therapies to manage heavy menstrual periods. Regular follow-up with a haematologist is essential to monitor the condition and adjust the management plan as needed, often within an NHS haemophilia centre.
UK care pathway
In the UK, individuals with suspected Von Willebrand disease are typically referred by their GP or another specialist to a haematologist, often at a specialised Haemophilia Centre, which are part of the NHS Genomic Medicine Service (GMS) network. These centres provide comprehensive care for bleeding disorders. Clinical genetic services can also facilitate genetic testing and provide counselling for families. Genetic testing for VWD is available through the NHS GMS, with the relevant R-code R355 used for VWF gene sequencing. Genetic counsellors can explain inheritance patterns, risks to family members, and the implications of genetic test results.
Frequently asked questions
Is Von Willebrand disease curable?
No, Von Willebrand disease is a lifelong inherited condition, meaning it cannot be cured. However, it can be effectively managed with various treatments to prevent and control bleeding episodes, allowing individuals to lead full and active lives.
How common is Von Willebrand disease?
Von Willebrand disease is considered the most common inherited bleeding disorder, affecting approximately 1% of the general population. However, many individuals with mild forms may not be diagnosed unless they experience significant bleeding or undergo specific testing.
Can women with VWD have children safely?
Yes, women with VWD can typically have children safely, but careful planning and management with a specialist haematology team are essential. Bleeding risks during pregnancy and childbirth need to be monitored and managed, often with specific treatments, to ensure the safety of both mother and baby.
What should I do if I think I have VWD?
If you suspect you or a family member might have Von Willebrand disease due to symptoms like easy bruising or excessive bleeding, you should consult your GP. They can refer you to a haematologist for appropriate diagnostic testing and management.
Are there different types of Von Willebrand disease?
Yes, there are three main types of Von Willebrand disease (Type 1, Type 2, and Type 3), with Type 2 having several subtypes. These types are based on whether there is a deficiency in VWF (Type 1 and 3) or if the VWF is present but not functioning correctly (Type 2). The type influences the severity of symptoms and the treatment approach.
References
- Weyand AC, Flood VH. Von Willebrand Disease: Current Status of Diagnosis and Management. Hematology/oncology clinics of North America. 2021. PMID: 34400042
- Leebeek FW, Eikenboom JC. Von Willebrand's Disease. The New England journal of medicine. 2016. PMID: 27959741
- Cooper S, Takemoto C. Von Willebrand disease. Pediatrics in review. 2014. PMID: 24585817
- Wilde JT. Von Willebrand disease. Clinical medicine (London, England). 2007. PMID: 18193717
- Hoyer LW. Pseudo-von Willebrand's disease. The New England journal of medicine. 1982. PMID: 6798443
- Pai-Dhungat J. Von Willebrand's Disease. The Journal of the Association of Physicians of India. 2020. PMID: 32978930
- Robertson J, Lillicrap D, James PD. Von Willebrand disease. Pediatric clinics of North America. 2008. PMID: 18381092
- Von Willebrand's disease. British medical journal. 1976. PMID: 1086116