Von Willebrand disease

Von Willebrand disease (VWD) is an inherited bleeding disorder. People with VWD have a problem with a protein in their blood called von Willebrand factor (VWF), which helps control bleeding. They either do not have enough of the protein, or it does not work the way it should. As a result, it takes longer for blood to clot and for bleeding to stop.

VWD is the most common inherited bleeding disorder. It affects both males and females from all backgrounds. It is thought that up to 1 in 100 people have VWD, but most have few symptoms, so many people do not know they have it.

How VWD affects people#

Most people with VWD are born with it. Sometimes it is detected in childhood, but others do not find out until they have a bleeding problem as an adult, such as heavy bleeding after a serious accident or a procedure. Some people only discover they have VWD after a relative is diagnosed and they are tested as well.

How severe VWD is depends on the type and on the level of von Willebrand factor in the blood. VWD is usually less severe than some other bleeding disorders. A small number of people have a severe form and may experience joint and muscle bleeds, similar to haemophilia.

VWD is a lifelong condition and there is no cure, but there are safe, effective treatments for all types.

Symptoms#

Symptoms vary greatly from person to person, and even members of the same family may have different symptoms. Many people have few or none. The more common symptoms involve the mucous membranes, the delicate tissues that line body passages such as the nose, mouth, uterus, vagina, stomach and intestines. They can include:

• Frequent or hard-to-stop nosebleeds
• Easy bruising
• Bleeding from the gums
• Heavy or prolonged bleeding from minor cuts
• Bleeding after injury, surgery or dental work that continues for a long time
• Very heavy or prolonged menstrual periods
• Heavy or prolonged bleeding after giving birth
• Blood in the faeces from bleeding in the stomach or intestines
• Blood in the urine from bleeding in the kidneys or bladder
• Bleeding that happens spontaneously, for no obvious reason

People with severe forms, particularly type 3, may also have bleeding into joints and muscles, which can cause swelling and pain.

The types of symptoms a person has can change over their lifetime. For example, a child may have nosebleeds and easy bruising that become less frequent as they grow older. However, their type of VWD will not change.

Women and girls#

Women are more likely to show symptoms than men. Without treatment, women with VWD often bleed more heavily or for longer during menstruation. Some also have heavy bleeding for days or weeks after giving birth or after pregnancy loss, and some have a lot of period pain or irregular periods.

These symptoms are not always caused by VWD and may have other causes, so an assessment by a gynaecologist is an important part of understanding and treating them.

Types of VWD#

There are three main types, and symptoms can vary from person to person within each type.

• Type 1 is the most common form, found in around 80 per cent of people with VWD. The von Willebrand factor works normally, but there is not enough of it. Symptoms are usually mild, depending on the level of VWF in the blood.
• Type 2 usually means the amount of VWF is normal, but it does not work properly. Type 2 is divided into subtypes 2A, 2B, 2M and 2N, which may be treated differently, so knowing the exact type is important.
• Type 3 is very rare. People with type 3 have very little or no VWF in their blood. Symptoms are more severe and can include joint and muscle bleeding.

How VWD is inherited#

Changes in the VWF gene can disrupt the formation of blood clots and cause VWD. You inherit two copies of the VWF gene, one from each parent.

Most cases of type 1 and type 2 are inherited in an autosomal dominant pattern, meaning one copy of the changed gene is enough to cause the condition. Type 3, some cases of type 2 and a small number of type 1 cases are inherited in an autosomal recessive pattern, meaning both copies of the gene must be changed. In these cases, each parent carries one copy of the gene change but has no symptoms themselves.

VWD affects males and females equally, and both sons and daughters can inherit it. Their symptoms may differ from their parents’ or from each other’s. Sometimes there is no family history and the genetic change arises spontaneously; even so, the person can pass the gene on to their own children.

If one family member is diagnosed, a doctor may recommend testing other relatives.

Some people develop a form of VWD later in life because of other medical problems that affect their von Willebrand factor. This is called acquired von Willebrand syndrome (AVWS) and is very rare.

How VWD is diagnosed#

Because symptoms are often mild, many people are not diagnosed until they have a major bleeding problem, for example from surgery or an injury. People with a severe form usually have major bleeding problems as a baby or small child and are often diagnosed within their first year.

Diagnosis involves a personal and family history of bleeding or bruising more than normal, along with specialised laboratory blood tests, including genetic testing that can identify a change in the VWF gene.

Routine blood tests often come back normal, which is why a person’s history of bleeding is so important. Testing is often repeated, because VWF and factor VIII levels can vary at different times. Things that can temporarily raise VWF levels, making results look normal, include stress, exercise, pregnancy, the normal hormonal changes of the menstrual cycle, hormone treatment, and inflammation from other health conditions. Blood type can also affect the level.

If you think you have a bleeding problem, it is important to see a haematologist who specialises in bleeding disorders. Ask your doctor or gynaecologist about a referral. Other family members may also need to be tested.

How VWD is treated#

Specialist bleeding-disorder services bring together a team of health professionals with expertise in caring for people with conditions such as VWD. The team may include haematologists (doctors who specialise in blood disorders), specialist nurses, social workers or counsellors, physiotherapists and other professionals. They can work with you to make a treatment plan and advise on living well with VWD.

The recommended treatment depends on the type of VWD and how severe it is. People with mild VWD often only need treatment for surgery, dental work, or an accident or injury, and some minor bleeding such as bruising may need no treatment at all.

Treatment options include:

• Desmopressin (DDAVP), a synthetic hormone that releases the body’s stored VWF and factor VIII into the bloodstream to help blood clot. It can be given as a slow injection into a vein, as an injection into the fatty tissue under the skin, or as a nasal spray. It is not suitable for everyone.
• Clotting factor concentrate containing von Willebrand factor and factor VIII, which replaces the missing proteins and helps blood to clot. It is made from donated human plasma and is injected into a vein. It is used when desmopressin is not suitable or when treatment is likely to be needed for more than two to three days.
• Tranexamic acid and aminocaproic acid, medicines that stop blood clots from being dissolved once they have formed. They can help with bleeding in the mouth, nosebleeds, gut bleeding and bleeding after dental work, minor surgery or injury. They are usually taken as tablets, syrup or a mouthwash, alone or together with desmopressin or a clotting factor concentrate.
• Fibrin glue, a medical gel made from fibrinogen and thrombin (proteins that help blood clot), applied directly onto a wound to stop bleeding.
• Hormone treatment, such as oral contraceptives, which can help women with heavy menstrual bleeding by raising VWF and factor VIII levels.

The right treatment varies depending on your medical needs, what works best for you and the situation. Your haematologist will consider all of this when working with you to choose the best option.

Living well with VWD#

VWD may be part of life, but it does not need to rule it. With the right care you can go to school, play sport, raise a family, work, travel and do the things you enjoy.

Physical activity#

Regular exercise is a great way to keep muscles and joints strong and stay healthy. It can help boost VWF levels and may even reduce the number of bleeding episodes. Being active with VWD is about balancing physical challenges with preventing injuries and dealing with any accidents quickly.

People with VWD often have to work out for themselves which activities suit them. Many people with mild VWD take part in all kinds of sport, including active and moderate-risk activities. People with type 3 or severe VWD may find that contact sports or high-injury activities can lead to serious bleeding, and may prefer lower-risk options or to modify their activities.

It is important to let children discover what they can safely do. As they grow up they will want to join in the same sports as their friends. Parents can help protect them by making sure they follow the usual safety guidelines for children in sport and by being prepared for accidents.

Travel#

If you are planning a trip, contact your bleeding-disorder service a few months before departure to plan ahead. They can advise on documentation, medication and travel insurance. You may need documentation to carry medication and treatment equipment through security and customs. It is also worth finding out, in case you need them, the names, addresses, phone numbers and opening hours of bleeding-disorder services along your route, and arranging travel insurance for trips abroad.

School#

Having VWD should not affect a child’s ability to attend childcare, kindergarten or school. Most bleeding with type 1 or type 2 VWD is not serious enough to keep a child home. Occasionally, with type 3 or severe VWD, a serious bleed into a muscle or joint may keep a child away from school, but with prompt treatment this should only be for a day or two. Helpful steps include:

• Giving information about VWD to childcare, kindergarten or school staff, including how to manage your child’s common bleeding problems such as nosebleeds
• Arranging an information session if useful; bleeding-disorder service staff are experienced in this and can help
• Asking staff to contact you at any time in an emergency, and providing the phone number of your bleeding-disorder service
• Teaching your child, when they are old enough, how to manage their own common bleeding problems

VWD issues for women and girls#

Heavy menstrual bleeding (menorrhagia) is a common symptom for women and girls with VWD. It may involve:

• Heavy periods, such as soaking through a tampon and pad about every two hours, or needing to change a pad during the night
• Passing large blood clots
• Periods lasting longer than normal, for example more than eight days
• Pain during periods (dysmenorrhoea)

Heavy bleeding can lead to anaemia (a low red blood cell count and low iron levels), with symptoms such as fatigue, paleness, lack of energy and shortness of breath. Some women and girls also have abdominal pain, and sometimes bleeding, around ovulation.

These can be symptoms of VWD, but they can also be signs of a gynaecological condition, so it is important to consult a gynaecologist. A comprehensive, holistic approach to care can help you achieve better health and quality of life. Specialist gynaecological care across your lifetime, including during family planning, is important for managing any issues that arise; these may not be related to VWD, but in some cases VWD can make bleeding worse.

Ideally your care team should work together and may include a gynaecologist, a haematologist who specialises in bleeding disorders, your doctor, and a paediatrician or obstetrician when relevant.

Pregnancy and family planning#

Most women with VWD do not have problems delivering a healthy baby. With the most common form (mild type 1), pregnancy often raises blood levels of VWF into the normal range by the last three months, so bleeding complications during pregnancy and childbirth are far less likely. Women with rarer or more severe forms are much more likely to need treatment to reduce the risk of bleeding during delivery.

If you are planning to have a child, talk to your bleeding-disorder service and your obstetrician before you become pregnant, and ask them to liaise with each other. You might also speak to a genetic counsellor. Prenatal diagnostic testing may be an option if the genetic change in your family is known; ask your haematologist whether any special care is needed for tests such as amniocentesis.

If you have VWD and are pregnant, let your care team know. You will need monitoring and blood tests for your VWF levels during the last three months to plan a safe delivery, and to plan any treatment needed to prevent heavy bleeding in the weeks after birth, when your factor levels return to their usual level.

Genetic counselling#

If you, your child or another family member has been diagnosed with VWD, or if it runs in your family, it may help to speak to a genetic counsellor. Genetic counsellors are health professionals qualified in both counselling and genetics. As well as offering emotional support, they can help you understand what causes VWD, how it is inherited, and what a diagnosis means for your or your child’s health and development, and for your family.

Genetic counsellors are trained to provide information and support that is sensitive to your family circumstances, culture and beliefs. If VWD runs in your family, they can explain the genetic testing options available to you and your relatives. You may choose to see a genetic counsellor when planning a family, to understand your chance of passing the condition on, or to arrange prenatal tests.

Key points#

• VWD is the most common inherited bleeding disorder
• It is thought that up to 1 in 100 people have VWD, but most have few symptoms
• Many people do not know they have VWD because their bleeding symptoms are very mild
• There are safe, effective treatments for all types of VWD
• VWD affects males and females equally, and both sons and daughters can inherit it