Von Willebrand disease (VWD) is a disorder in which the blood does not clot properly, resulting in longer or more frequent bleeding. VWD is caused by a deficiency or dysfunction of von Willebrand factor, a blood protein needed for normal clotting. While it is less well known than hemophilia, VWD is the most common inherited bleeding disorder. It affects up to 1 in 500 people in the United States. The mutations in the von Willebrand factor gene that cause VWD can run in families and affects males and females equally, although, clinically, VWD is more common in biological females.

People with VWD may experience easy bruising, frequent or hard-to-stop nosebleeds, heavy or prolonged menstrual bleeding, or excessive bleeding after injury, surgery, dental work, or childbirth. In more severe cases, bleeding may occur after minor trauma or without an obvious cause, and some people may have gastrointestinal bleeding or bleeding into joints and/or muscles. However, symptoms are more likely to be noticeable in women because of increased bleeding during menstrual periods or after childbirth.

Although VWD is a lifelong condition, most people with VWD can live healthy, active lives with proper treatment and care.

Von Willebrand disease is caused by a deficiency or dysfunction of von Willebrand factor, a protein essential for forming stable blood clots that stop bleeding. In healthy people, von Willebrand factor helps blood platelets stick to vessel walls at injury sites. It also carries and protects another clotting protein, factor VIII (factor eight). In VWD, people either have too little von Willebrand factor or the von Willebrand factor the body makes does not work correctly. As a result, clots do not form properly.

VWD leads to a tendency to bleed easily and for longer periods, especially from mucous membranes such as those in the nose, mouth, gastrointestinal tract, and uterus. People with VWD may also bruise easily and bleed from minor injuries.

There are three main types of inherited VWD:

• Type 1: The mildest and most common form of VWD, type 1 accounts for around 85% of all cases. People with this type of VWD have reduced blood levels of von Willebrand factor and may also have low levels of factor VIII.
• Type 2: In this type of VWD, the body produces von Willebrand factor that does not function properly. Four subtypes (2A, 2B, 2M, and 2N) each affect the protein in different ways.
• Type 3: The rarest and most severe form of VWD, type 3 is characterized by an absence of von Willebrand factor and low levels of factor VIII.

Some people with VWD have mild symptoms and may not be diagnosed with the condition until they undergo surgery or have an injury that results in excessive bleeding. Others have symptoms early in life and are diagnosed during childhood. Women are more likely than men to be aware of symptoms because they may experience increased bleeding during menstruation or after childbirth.

VWD is most often caused by changes (known as variants or mutations) in the von Willebrand factor gene, which provides instructions for making von Willebrand factor. These changes can result in too little of the protein or in the protein not functioning correctly. Without functioning von Willebrand factor, blood cannot clot normally, leading to prolonged or excessive bleeding.

Different gene variants result in the different types of inherited VWD:

• Type 1: Caused by variants that reduce the amount of von Willebrand factor.
• Type 2: Caused by variants that make the von Willebrand factor protein function abnormally.
• Type 3: Caused by variants that result in an absence of von Willebrand factor in the blood.

Most VWD cases run in families, with the altered gene passed down from one or both parents. Type 1 and most type 2 cases are inherited in an autosomal dominant pattern, meaning one changed gene variant (inherited from one parent) is enough to cause the disorder. Type 3 and some type 2 cases are autosomal recessive, meaning two copies of the mutated gene must be inherited (one from each parent) to cause the condition.

In rare cases, people can acquire VWD later in life due to other medical conditions or medications that affect von Willebrand factor levels. Certain cancers, autoimmune diseases, or heart and blood vessel diseases can lead to the breakdown or clearing of von Willebrand factor in the body. Some medications, such as valproic acid, ciprofloxacin, and others, can result in VWD. This acquired form is not inherited.

Symptoms may include:

• Frequent nosebleeds that start spontaneously and last longer than 10 minutes
• Gum bleeding when a new tooth comes in
• Easy bruising, sometimes without obvious cause
• Prolonged bleeding from minor wounds
• Heavy or prolonged menstrual bleeding
• Excessive bleeding after injury, surgery, dental work, or childbirth
• Gastrointestinal bleeding
• Blood in the stool or urine
• Bleeding into joints or muscles (especially in severe cases)
• Iron deficiency (anemia) caused by blood loss
  

The severity of symptoms varies, even among people with the same type of VWD. Symptoms may fluctuate over time and with different life circumstances, such as pregnancy, illness, or age. In severe cases, bleeding can occur without an obvious cause.

Many people with mild VWD do not notice symptoms until they have a major injury, surgery, or dental work. Others have symptoms early in life and are diagnosed during childhood. Women are more likely than men to be aware of symptoms because they may experience increased bleeding during menstruation or after childbirth.

To diagnose VWD, your doctor will review your medical and family history, conduct a physical exam, and order blood tests.

Your doctor will ask you about your symptoms, such as when they began and their severity. They may administer a standardized questionnaire, called the Bleeding Assessment Tool (BAT), that helps your doctor evaluate your bleeding symptoms and history. Your doctor may also ask if any of your relatives has VWD or a history of bleeding problems. During the physical exam, your doctor will check for signs of VWD, such as bruises or petechiae (tiny red spots caused by bleeding beneath the skin).

Tests may include:

• von Willebrand factor antigen test to measure the amount of von Willebrand factor in your blood
• von Willebrand factor activity test to check how well von Willebrand factor is working
• Factor VIII activity test to measure factor VIII levels in the blood.
• Platelet function tests to see how well your platelets are working
• von Willebrand factor multimer analysis to examine the structure and size of von Willebrand factor and help identify the type of VWD

Your doctor may also recommend genetic testing to identify changes in the von Willebrand factor gene, especially if the diagnosis is unclear or they suspect a severe type.

Levels of clotting proteins can change due to stress, illness, pregnancy, or other factors. Your provider may need to repeat tests to make a diagnosis.

Treatments for VWD help control bleeding, prevent complications, and improve quality of life. Treatment depends on the type and severity of VWD and the situation in which bleeding occurs. Some people with VWD do not require any treatment.

Commonly used treatments include:

• Desmopressin: This medication stimulates the release of stored von Willebrand factor, temporarily increasing its level. Desmopressin comes as an injection, nasal spray, or infusion and is often used before surgery or dental work. Desmopressin may not work for all patients or situations, especially type 3 or some type 2 subtypes.
• Antifibrinolytic medications: Drugs such as tranexamic acid or aminocaproic acid help prevent clots from breaking down and can help control bleeding in the mouth, after dental work, during surgery, or for heavy menstrual bleeding. They are available as pills, mouthwash, or injections.
• Replacement therapy: Infusions of concentrated von Willebrand factor and factor VIII increase blood levels of these proteins, especially in people with severe VWD or who do not respond to desmopressin. Replacement therapy is used for serious bleeding, before surgery, or for managing heavy menstrual bleeding or childbirth. Some people with severe VWD and frequent or severe bleeding may need regular preventive infusions of von Willebrand factor concentrates.
• Hormonal therapy: For women with heavy menstrual bleeding, hormone-based treatments such as oral contraceptives or hormone-releasing intrauterine devices can help reduce bleeding and prevent anemia.

In addition to these treatments, special dressings, gels, or topical medications can help stop minor bleeding. If you develop anemia from blood loss, your health care provider may recommend iron supplements.

Prevention plays a key role in managing most cases of VWD. If you have VWD, you should avoid medications that increase bleeding, such as aspirin or NSAIDs. Always inform health care providers of your condition before surgery, dental work, or childbirth.

People with VWD may develop iron deficiency (anemia), especially with chronic or heavy bleeding. In rare cases, people with type 3 VWD who receive frequent replacement therapy may develop antibodies against von Willebrand factor. These antibodies, which are part of the immune system, can reduce the efficacy of treatment and result in anaphylaxis, a life-threatening allergic reaction. People with severe VWD are at higher risk for joint damage from repeated joint bleeds or severe bleeding after surgery or childbirth.

The outlook for people with VWD depends on several factors, including the type and severity of the disease, the person’s symptoms, and how well the condition is managed. Many people with mild VWD can lead normal, active lives and may experience only occasional or minor bleeding, such as after surgery, injury, or dental work. With careful planning and monitoring, women with VWD can have successful pregnancies and healthy children.

For those with more severe forms, bleeding may occur frequently or become harder to control, especially after surgery, childbirth, or injury. Regular care with a hematologist or a comprehensive bleeding disorder program helps ensure that people with VWD receive the right care.

With proper diagnosis, regular follow-up, and access to effective treatments, most people with VWD can control bleeding, prevent complications, and take part in everyday activities.

“At Yale Medicine’s Center for Bleeding and Clotting Disorders, together with the Center of Excellence for Classical Hematology at Smilow Cancer Hospital, people with von Willebrand disease and related conditions receive truly comprehensive, multidisciplinary, and individualized care—delivered with state-of-the-art expertise and an unwavering commitment to excellence,” says Anish Sharda, MD, a Yale Medicine hematologist who specializes in the treatment of bleeding, clotting, and platelet disorders. “Our team brings together experienced adult and pediatric hematologists, nurse practitioners, nurses, physical therapists, social workers, and collaborating specialists in fields such as gynecology and maternal–fetal medicine, ensuring truly holistic care. This integrated approach not only addresses the medical complexity of von Willebrand disease, but also supports patients and families with compassion, innovation, and hope.”