Patient information: von Willebrand disease

VON WILLEBRAND DISEASE OVERVIEW

When people think of medical disorders that cause excessive or uncontrolled bleeding, they usually think of hemophilia. That's understandable, given that hemophilia is often mentioned in popular culture. But, the truth is that von Willebrand disease is a much more common bleeding disorder than hemophilia, affecting roughly 1 percent of the population.

Although more common than hemophilia, von Willebrand disease is often less serious. Many people with von Willebrand disease have such mild symptoms that they do not learn they have the disorder until well into adulthood. Often the first clues come during surgery or after a serious injury, when bleeding will not stop.

If you are cut or injured, tiny cell fragments that circulate in the blood, called platelets, collect at the site to form a plug to stop the bleeding. Von Willebrand factor is essential to this process, because it is the "glue" that binds platelets to one another and to the lining of the blood vessel. Von Willebrand factor also protects another important clotting factor (factor 8, written as factor VIII), from being broken down.

Von Willebrand disease is most often caused by genetic mutations that either impair your ability to make von Willebrand factor or lead to the production of defective forms of the protein. In rare instances, von Willebrand disease can be "acquired," meaning it is not inherited and instead arises because of the presence of another illness or the use of certain drugs.

TYPES OF VON WILLEBRAND DISEASE

The inherited forms of von Willebrand disease come in three different types:

Type 1 — Type 1 is the most common form, affecting 75 percent of those who have the disorder. People with this type make insufficient amounts of von Willebrand factor.

Type 2 — Type 2 is the second most common form, and causes people to make defective forms of von Willebrand factor. This type can be broken down into 4 different subtypes. If you have type 2, your healthcare provider can explain the subtype you have in more detail.

Type 3 — Type 3 is the rarest form of von Willebrand disease, and causes a total deficiency of the protein. This type is usually detected early in life because it leads to the most severe and apparent symptoms of the disease.

Finding out which type you have is an important step in getting the right treatment. Knowing what type you have is also important in helping healthcare providers control bleeding in emergency situations. (See "Classification and pathophysiology of von Willebrand disease".)

Carry this information and a list of any other medical problems and medications on a medical identification card or bracelet (see 'Lifestyle changes and self care with von Willebrand disease' below.

VON WILLEBRAND DISEASE SYMPTOMS

The symptoms of von Willebrand disease are often very mild. Sometimes, a person will learn that something is wrong only after they are faced with a "bleeding challenge," such as a major injury, surgery, or childbirth. However, once you learn that you have the disorder, you may remember instances in which you bled more than normal. For example, you may recall:

• Getting frequent or long-lasting nosebleeds
• Gum bleeding with no apparent cause
• Bruising easily with lumps forming under the bruise
• Having especially heavy or long-lasting periods (if you are a woman), lasting longer than seven to 10 days and with large blood clots
• Bleeding more than expected during dental work or minor medical procedures and for a prolonged time after surgical procedures
• Bleeding when you took aspirin or related drugs called nonsteroidal anti-inflammatory drugs (NSAIDs), all of which inhibit clotting

VON WILLEBRAND DISEASE DIAGNOSIS

If your healthcare provider suspects you have von Willebrand disease, he or she will want to learn as much as possible about your "bleeding history." He or she will ask if you often get nosebleeds, bruise easily, or have had any of the other symptoms mentioned above. Since von Willebrand disease runs in families, your healthcare provider will also want to know if any of your relatives have the disorder. (See "Clinical presentation and diagnosis of von Willebrand disease".)

Lab tests — You may have to provide one or more blood samples so that your healthcare provider can measure how much von Willebrand factor you make and test whether your version of the protein functions normally.

The initial tests used to diagnose von Willebrand disease include the:

• von Willebrand factor antigen test — This test measures the amount of von Willebrand factor in your blood.
• von Willebrand factor activity test — This test measures how well your von Willebrand factor works.
• Factor VIII activity test — Factor VIII (factor 8) is another protein involved in clotting and is carried in the blood, attached to and protected by von Willebrand factor. Because of this, your healthcare provider will also determine the levels of factor VIII in your blood.

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

When any of these more complex tests are performed, your clinician will notify you of the results and what they mean in terms of classifying your type of von Willebrand disease. He or she can also discuss which form(s) of treatment might be required.

LIFESTYLE CHANGES AND SELF CARE WITH VON WILLEBRAND DISEASE

If you are diagnosed with von Willebrand disease, your healthcare provider may recommend that you avoid aspirin, NSAIDs (ibuprofen/Advil®, naproxen/Aleve®, and others), and any other drugs that inhibit clotting or "thin the blood." If you need a medication for pain or fever relief, acetaminophen (Tylenol®) is a safe alternative to aspirin and NSAIDs.

Depending on the severity of your von Willebrand disease, you may also have to take special precautions to avoid injuries, such as avoiding contact sports. However, precautions are not necessary for most people with type 1 or type 2 von Willebrand disease.

Planning for surgery and childbirth — If you learn that you need surgery, including dental surgery, you should discuss your von Willebrand disease with your surgeon or dentist ahead of time.

If you become pregnant or want to do so, you should also discuss your von Willebrand disease with your obstetrician or primary care doctor. These discussions will help your healthcare providers develop a plan to control your bleeding before it becomes a problem.

VON WILLEBRAND DISEASE TREATMENT

Once your healthcare provider knows what type of von Willebrand disease you have, he or she can recommend an appropriate treatment. You and your healthcare provider may have to try a few different treatment regimens before you find the one that works best for you. (See "Treatment of von Willebrand disease".)

Depending on the type and severity of von Willebrand disease you have, you may get treatments that:

• Increase your own production of von Willebrand factor — This is usually done with a drug called desmopressin (DDAVP®; Stimate®), which you can take as a nasal spray or as an injection. Your clinician will give you more detailed instructions as to how to use this medication, how often it can be repeated, what side effects to watch for, and when to call if the medication does not slow your bleeding.

It is important to understand how to use DDAVP since it can cause unwanted and serious side effects if used at a higher dose or for a longer period than recommended.

• Replace your missing or deficient von Willebrand factor — This is usually done by injecting purified forms of the protein directly into your veins. A number of such products are available, including Humate P® and Alphanate®. This treatment is done in the hospital or a healthcare provider's office.
• Prevent clots from dissolving — This approach involves taking medications, such as aminocaproic acid (Amicar®) or tranexamic acid (Cyklokapron®), in pill form, as a mouthwash, or as an injection that is given into a vein. These medications are especially useful for managing nosebleeds or bleeding from the mouth (for example, following dental work).
• Stimulate clot formation — Medications that stimulate the formation of clots are available as a foam strip or gel that is applied to the bleeding area. Your healthcare provider may use this type of treatment for bleeding from the mouth or nose.

Hormones help control menstrual bleeding — Women with von Willebrand disease are sometimes given hormone treatment in the form of menopausal hormone therapy, the birth control pill, or an intrauterine device (IUD) that releases a hormone called progestin. These hormonal treatments can eliminate or reduce heavy menstrual bleeding. (See "Patient information: Hormonal methods of birth control" and "Patient information: Postmenopausal hormone therapy".)

Acquired von Willebrand disease — People whose von Willebrand disease is associated with another medical condition, such as autoimmune diseases, cancer, or reduced function of the thyroid gland, are sometimes given treatments similar to those described above. For them, treating the underlying condition may also be important in managing the von Willebrand disease.

Pregnancy and childbirth in women with von Willebrand disease — Women with von Willebrand disease should be monitored closely throughout pregnancy to make sure that bleeding does not become an issue. Most will not need treatment while they are pregnant, because von Willebrand factor production naturally rises during pregnancy. After delivery, however, levels of the protein can drop and lead to serious bleeding. As a result, women may need to take one or more of the treatments described above for one to three weeks following delivery.

WHERE TO GET MORE INFORMATION

Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two people are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.

This discussion will be updated as needed every four months on our web site (www.uptodate.com/patients). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.

Some of the most pertinent include:

Patient Level Information:
Patient information: Hormonal methods of birth control
Patient information: Postmenopausal hormone therapy

Professional Level Information:
Approach to the adult patient with a bleeding diathesis
Biology and normal function of von Willebrand factor
Classification and pathophysiology of von Willebrand disease
Clinical presentation and diagnosis of von Willebrand disease
Treatment of von Willebrand disease

A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable.

• National Library of Medicine

      (www.nlm.nih.gov/medlineplus/healthtopics.html)

• National Heart, Lung, and Blood Institute

      (www.nhlbi.nih.gov/index.htm)

• National Hemophilia Foundation

      (www.hemophilia.org)

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