Patient education: von Willebrand disease (Beyond the Basics)

VON WILLEBRAND DISEASE OVERVIEW — von Willebrand disease (VWD) is a bleeding disorder. It can be inherited or, less commonly, develop later in life (this type of VWD is not heritable and is referred to as acquired von Willebrand syndrome [AVWS]).

The amount of bleeding and need for treatments varies widely from person to person, with some never needing treatment (or even knowing they have the disease) to others with more severe bleeding that might require specialized treatments.

A person may suspect they have VWD if they have excessive bleeding, typically from mucous membranes (mouth, nosebleeds, heavy menstrual bleeding, bleeding after delivering a baby, or gastrointestinal tract bleeding). This is especially true if VWD runs in the family. Because the symptoms can be mild, people may not discover that they have VWD until adulthood. (See 'von Willebrand disease symptoms' below.)

In people with VWD, a protein called von Willebrand factor (VWF) is deficient or does not function properly. There are different types of inherited VWD; some cause low levels of VWF, and others cause the production of VWF that does not function correctly. (See 'Types of von Willebrand disease' below.)

The major function of VWF in the body is to help platelets, the cells that initiate normal blood clotting, to attach to the lining of the blood vessels in areas of injury. VWF also helps protect one of the blood clotting factors, factor eight (designated with the Roman numeral as factor VIII), from being destroyed. Some people with VWD have low platelet counts or low factor VIII levels, but many do not. In either case, the diagnosis of VWD is made by specific blood tests for VWF and factor VIII amount and function.

More detailed information about VWD, written for health care providers, is available by subscription. (See 'Professional level information' below.)

TYPES OF VON WILLEBRAND DISEASE — There are three major types of inherited von Willebrand disease (VWD), named 1, 2, and 3:

●Type 1 is the most common form, affecting approximately three-quarters of people who have inherited VWD. People with this type have low levels of VWF in the blood due either to not making enough von Willebrand factor (VWF) or to having abnormally fast removal of VWF from the bloodstream.

●Type 2 is the second most common form. People with this type make a VWF protein that does not function normally. There are subtypes of type 2 that have different characteristics.

●Type 3 is the rarest form of VWD. People with type 3 do not make any VWF at all. This type is usually detected early in life because it leads to the most severe bleeding symptoms.

It is also possible to have acquired von Willebrand syndrome (AVWS). People with AVWS have a non-genetic condition that affects VWF levels. One example is an autoimmune disease such as systemic lupus erythematosus (also called "lupus"), in which the body produces antibodies against normal tissues, sometimes including antibodies directed against VWF. The antibodies bind to circulating VWF and cause the body to remove the antibody and VWF together so that there is not enough VWF in the bloodstream. Other examples are listed in the table (table 1).

Finding out which type of VWD you have is an important step in getting the right treatment. Knowing what type you have is particularly important in helping health care providers control bleeding in emergency situations.

VON WILLEBRAND DISEASE SYMPTOMS — The symptoms of von Willebrand disease (VWD) vary from mild to severe in different individuals. Excess bleeding can occur with menstrual periods, surgery, dental procedures, childbirth, or serious injury. Commonly, people can have bruising in the absence of trauma or menstrual bleeding that is severe enough to cause iron deficiency or, less commonly, require blood transfusion.

Usually the bleeding in VWD is from mucosal surfaces such as the mouth and nose, gastrointestinal tract, or uterus and vagina.

Sometimes a person will learn that something is wrong only after they have a "bleeding challenge" such as surgery or childbirth. Once you learn that you have the disorder, you may remember instances in which you bled more than normal. For example, you may recall:

●Frequent or long-lasting nosebleeds (nosebleeds lasting longer than 10 minutes or requiring medical attention)

●Gum bleeding with no apparent cause

●Bruising easily with lumps forming under the bruise, or bruising without any recognized injury that caused the bruise

●Having especially heavy or long-lasting menstrual periods, persisting more than 7 days and with large blood clots

●Having especially heavy bleeding after delivering a baby or bleeding that lasts 6 weeks or longer after delivery

●Bleeding more than expected during or after dental work or minor medical procedures and for a prolonged time after surgical procedures

●Having more severe bleeding, such as in the stomach or intestines, or into a joint, although this is less common

●An occasional nosebleed due to dry air or a bad cold, or a bruise at the site of an injury, are not usually signs of VWD.

VON WILLEBRAND DISEASE DIAGNOSIS

Bleeding history — If your health care provider suspects you have von Willebrand disease (VWD), they will want to learn as much as possible about your bleeding history. They will ask if you often get nosebleeds, bruise easily, or have had any of the other symptoms mentioned above. They might administer a Bleeding Assessment Tool (BAT) that generates a bleeding score. A self-administered version of a BAT can also be used; an example is available at https://letstalkperiod.ca.

Some of the major clues to the severity of bleeding include whether you required a doctor's visit or a blood transfusion, whether you needed packing placed in your nose or mouth (to control the bleeding), and whether you developed iron deficiency and had to take iron supplementation.

Since VWD usually runs in families, your health care provider will also want to know if any of your relatives have the disorder or have a history of unusual bleeding, especially if it was severe or required a transfusion or additional surgery.

If the VWD appears to be new in an older person (someone without a personal or family history of bleeding), the provider may ask about symptoms of associated diseases that might cause acquired VWD.

Lab tests — The testing for VWD is done on one or more blood tests.

The initial tests used to diagnose VWD include:

●von Willebrand factor (VWF) antigen — This measures the amount of VWF in your blood.

●VWF activity — This may also be called platelet-dependent VWF activity. There are several tests that can be used to measure how well your VWF works. Examples include the ristocetin cofactor test (abbreviated VWF:RCo) or VWF:GPIbM.

●Factor VIII activity — VWF stabilizes one of the other blood clotting factors, factor VIII (factor eight) (see 'von Willebrand disease overview' above), and factor VIII levels can be low in VWD. Factor VIII can also be low in hemophilia A; the laboratory will consider all the results together if there is a question of which condition is present.

If any of these tests are abnormal, your health care provider may repeat the tests and/or run additional, more sophisticated tests. The results of all of these tests will help your health care provider determine what type of VWD you have and how severe it is.

If you have any of these tests done, your health care providers will notify you of the results and what they mean in terms of diagnosis and classifying your type of disease. They can also discuss which form(s) of treatment you might need.

VON WILLEBRAND DISEASE TREATMENT

Reducing the risk of bleeding — If you are diagnosed with von Willebrand disease (VWD), your health care provider may recommend that you avoid medications that interfere with the function of your platelets. These might include aspirin and medications known as NSAIDs, such as ibuprofen (sample brand names: Advil, Motrin) and naproxen (brand name: Aleve). If you need a medication for pain or fever relief, acetaminophen (brand name: Tylenol) is a good alternative to aspirin and NSAIDs.

Depending on the severity of your VWD, you may also have to take special precautions to avoid injuries, such as avoiding contact sports. However, such precautions are not necessary for most people with type 1 and those with milder forms of type 2 VWD.

If you learn that you need a medical procedure or surgery, including dental surgery, you should discuss your VWD with your health care providers ahead of time. Your type of VWD, previous history of bleeding, and options to control bleeding will be discussed.

●People with VWD will generally need closer-than-average monitoring during and after surgery.

●Some people will not need any additional treatment.

●DDAVP – Some people can be treated with a medicine called DDAVP (also called desmopressin; sample brand name Stimate). This medicine helps your body release extra von Willebrand factor into the bloodstream. However, this effect lasts only for 6 to 24 hours and may not be sufficient for some people.

The only way to know if DDAVP will work for you is to do a test after your diagnosis is established and when you are not bleeding or otherwise sick. During the test, you are given a dose of DDAVP and your blood is checked before and after the dose to see if your VWF and factor VIII levels increase sufficiently, usually into the normal range.

DDAVP can be given as an injection or a nose spray. If you are a person who is helped by the DDAVP nose spray, it is important to use the form intended for VWD (there are other forms intended to treat other conditions, such as fluid disorders or bedwetting).

It is also important not to drink too much water while taking DDAVP, as DDAVP can cause water retention that can lead to serious symptoms. Some older people or people with heart disease or a history of stroke may also need to avoid using DDAVP.

●Medications that prevent clot breakdown – Individuals with VWD may be treated with a medication that prevents blood clots from dissolving, referred to as antifibrinolytic agents. Examples of these types of medications include aminocaproic acid (brand name: Amicar) and tranexamic acid (brand name: Cyklokapron). These medications can be given in pill form, as a mouthwash, or as an injection into a vein.

These medications are especially useful for managing bleeding from mucosal surfaces, such as nosebleeds or bleeding from the mouth following dental work, and they are often given in addition to other treatments for VWD.

●Treatment at the bleeding site – Some people will also benefit from application of a foam or gel to the bleeding site that stimulates clots to form right at that spot.

●VWF concentrates – Some people will need a stronger treatment such as administration of von Willebrand factor; these products are purified from human plasma or produced in a laboratory. Examples of plasma-derived product brand names include Humate P, Alphanate, Koate, and Wilfactin. An example of a product manufactured in the laboratory is Vonvendi. These treatments are injected into a vein, often in the hospital or in a health care provider's office, but some patients are taught how to self-inject this treatment at home.

●Treatment of another disorder – People with acquired VWS often benefit with improvement in their AVWS when they are treated for the associated condition (table 1). The other measures listed above, and some additional medications, may also be given.

Treatment of severe bleeding — If you are in an accident or have severe bleeding with surgery despite receiving the treatments above, you may be given platelet transfusions, additional von Willebrand factor, and/or other medications. It may be necessary to receive treatment for several days when severe bleeding occurs.

It is important to carry information about your VWD, including what type of VWD you have (see 'Types of von Willebrand disease' above), and a list of any other medical problems and medications, on a medical identification card or bracelet. This will help your health care providers know what type of treatment is likely to work best for you.

Treatment of recurrent bleeding — Some individuals with severe VWD who have repeated, frequent bleeding in an area such as in a joint or from the gastrointestinal tract may benefit from injections of a VWF concentrate on a regular basis, often two to three times weekly.

Treatment for control of menstrual bleeding — People with VWD who have heavy periods are sometimes treated with hormones, such as birth control pills or a progestin-releasing intrauterine device (IUD).

Some people also benefit from DDAVP or an antifibrinolytic medicine that prevents the breakdown of clots (for example, tranexamic acid; brand name Cyklokapron). These treatments can reduce heavy menstrual bleeding. In some patients for whom these measures are not effective, a VWF concentrate is given. (See "Patient education: Hormonal methods of birth control (Beyond the Basics)".)

Treatment during pregnancy and childbirth — Many people with VWD who become pregnant can have a normal pregnancy without bleeding complications.

However, as with surgery, it is important to have proper monitoring and to know what treatments will work well for you if you do have excessive bleeding. If you get pregnant or want to try to get pregnant, you should discuss your VWD with your health care provider. A specialist with expertise in managing pregnancy in people with VWD should be involved, and close monitoring during the pregnancy is appropriate.

These discussions will help your health care providers develop a plan to control any excessive bleeding before it becomes a problem.

Many people will not need treatment while they are pregnant, because von Willebrand factor levels naturally increase during pregnancy. After delivery, however, levels of the protein can decline dramatically and lead to serious bleeding. One or more of the treatments described above may be used for one to three weeks following delivery.

A clinician with expertise in genetic counseling or a provider with expertise in the genetics of VWD can help you determine the likelihood that your child will inherit VWD. For most types of inherited VWD, the chance of a child inheriting the condition is approximately 50 percent. A pediatrician can discuss with you whether and when your child needs to be tested.

WHERE TO GET MORE INFORMATION — Your health care provider is the best source of information for questions and concerns related to your medical problem.

This article will be updated as needed on our web site (www.uptodate.com/patients). Related topics for patients, as well as selected articles written for health care professionals, are also available. Some of the most relevant are listed below.

Patient level information — UpToDate offers two types of patient education materials.

The Basics — The Basics patient education pieces answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials.

Patient education: von Willebrand disease (The Basics)
Patient education: Taking care of bruises (The Basics)

Beyond the Basics — Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are best for patients who want in-depth information and are comfortable with some medical jargon.

Patient education: Hormonal methods of birth control (Beyond the Basics)

Professional level information — Professional level articles are designed to keep doctors and other health professionals up-to-date on the latest medical findings. These articles are thorough, long, and complex, and they contain multiple references to the research on which they are based. Professional level articles are best for people who are comfortable with a lot of medical terminology and who want to read the same materials their doctors are reading.

Approach to the adult with a suspected bleeding disorder
Pathophysiology of von Willebrand disease
Clinical presentation and diagnosis of von Willebrand disease
von Willebrand disease (VWD): Treatment of major bleeding and major surgery
von Willebrand disease (VWD): Treatment of minor bleeding, use of DDAVP, and routine preventive care
Acquired von Willebrand syndrome

The following organizations also provide reliable health information.

●National Library of Medicine

     (https://medlineplus.gov/healthtopics.html)

●National Heart, Lung, and Blood Institute

     (www.nhlbi.nih.gov/)

●National Hemophilia Foundation

     (www.hemophilia.org)