Patient education: von Willebrand disease (Beyond the Basics)
- Margaret E Rick, MD
Margaret E Rick, MD
- Adjunct Clinical Professor of Medicine
- Uniformed University of the Health Sciences, Bethesda, MD
VON WILLEBRAND DISEASE OVERVIEW
von Willebrand disease (VWD, also called von Willebrand syndrome) is a bleeding disorder. It can be inherited or, less commonly, develop later in life (this is referred to as acquired VWD). The amount of bleeding and need for treatments varies widely, from a person never needing treatment (or even knowing they have the disease) to more severe bleeding that might require specialized treatments.
Symptomatic VWD is uncommon, and many people who are concerned about excessive bruising or heavy menstrual bleeding do not have VWD (or any bleeding disorder). However, VWD is more common than some other conditions such as hemophilia, and if a person is truly experiencing excessive bruising or bleeding, it is important to check for VWD. Women often report bruising and excessive bleeding with menstrual periods or childbirth, but VWD affects men just as often as women; men, however, frequently report fewer symptoms. Because the symptoms are often mild, people may not discover that they have VWD until adulthood. (See 'von Willebrand disease symptoms' below.)
In people with VWD, a protein in the body called von Willebrand factor (VWF) is deficient or abnormal. There are different types of VWD; some cause low levels of VWF, and others cause the production of abnormal forms of VWF that do 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, called factor eight (typically abbreviated with the Roman numeral 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.
More detailed information about VWD, written for healthcare providers, is available by subscription. (See 'Professional level information' below.)
TYPES OF VON WILLEBRAND DISEASE
There are three major forms of inherited von Willebrand disease (VWD), named 1, 2, and 3:
●Type 1 is the most common form, affecting about three-quarters of people who have inherited VWD. People with this type do not make enough von Willebrand factor (VWF) or have abnormally fast removal of VWF from the bloodstream.
●Type 2 is the second most common form. People with this type make VWF, but the function of the protein is abnormal. 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 or have extremely fast removal of VWF from the bloodstream. This type is usually detected early in life because it leads to the most severe bleeding symptoms.
Finding out which type you have is an important step in getting the right treatment. Knowing what type you have is particularly important in helping healthcare providers control bleeding in emergency situations.
VON WILLEBRAND DISEASE SYMPTOMS
The symptoms of von Willebrand disease (VWD) are often very mild. Bleeding in VWD is frequently related to stresses on the system such as menstrual periods, surgery, childbirth, or serious injury. In addition, some people have bruising, even in the absence of trauma, or menstrual bleeding that is severe enough to cause iron deficiency or 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 are faced with stress on the system, also called a "bleeding challenge." 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:
●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 to 10 days and with large blood clots
●Having especially heavy bleeding after delivering a baby (bleeding can even occur as late as 5 to 20 days 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 or in the urine, although this is less common
In contrast, 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 von Willebrand disease.
VON WILLEBRAND DISEASE DIAGNOSIS
Bleeding history — If your healthcare provider suspects you have von Willebrand disease (VWD), 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. 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 became iron deficient and had to take iron.
Since VWD runs in families, your healthcare 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.
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 von Willebrand factor functions normally.
The initial tests used to diagnose VWD 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. A commonly used von Willebrand factor activity test is called the Ristocetin cofactor test.
●Factor VIII activity test — Factor VIII (factor eight) is another protein involved in clotting; it circulates 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 VWD you have and how severe it is.
If you have any of these tests done, your healthcare provider will notify you of the results and what they mean in terms of diagnosis and classifying your type of disease. He or she 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 healthcare provider may recommend that you avoid medications that inhibit clotting or "thin the blood." 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, 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 healthcare 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.
●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 a day or two and may not be sufficient for some people. The only way to know if it will work for you is to do a test after your diagnosis is established and when you are not bleeding; during the test, you are given a dose of DDAVP and your blood is checked before and after the dose to see if it helped. 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, as DDAVP can cause water retention that can cause serious symptoms. Some people with heart disease may also need to avoid using DDAVP.
●Individuals with VWD may be treated with a medication that prevents blood clots from dissolving. 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.
●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.
●Some people will need a stronger treatment such as administration of von Willebrand factor; these products are prepared 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, generally in the hospital or a healthcare provider's office.
●People with acquired VWD often benefit with improvement in their VWD when they are treated for an associated condition such as an autoimmune disease or cancer or other underlying condition. 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 and other medications in addition. 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 healthcare providers know what type of treatment is likely to work best for you.
Treatment for control of menstrual bleeding — Women with VWD who have especially heavy periods are sometimes treated with hormones, such as birth control pills or a progestin-releasing intrauterine device (IUD). These treatments can reduce heavy menstrual bleeding. (See "Patient education: Hormonal methods of birth control (Beyond the Basics)".)
Treatment during pregnancy and childbirth — Most women with VWD who become pregnant have a normal pregnancy without any 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 healthcare provider. A specialist with expertise in managing pregnancy in people with VWD should be involved.
These discussions will help your healthcare providers develop a plan to control your bleeding before it becomes a problem. Women with VWD 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. Because of this, you may need to take one or more of the treatments described above for one to three weeks following delivery.
A clinician with expertise in genetics 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 about 50 percent. A pediatrician can discuss with you whether and when your child needs to be tested.
WHERE TO GET MORE INFORMATION
Your healthcare 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 healthcare 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.
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.
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 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
The following organizations also provide reliable health information.
●National Library of Medicine
●National Heart, Lung, and Blood Institute
●National Hemophilia Foundation
- Mannucci PM. Treatment of von Willebrand's Disease. N Engl J Med 2004; 351:683.
- Pasi KJ, Collins PW, Keeling DM, et al. Management of von Willebrand disease: a guideline from the UK Haemophilia Centre Doctors' Organization. Haemophilia 2004; 10:218.
- Nichols WL, Hultin MB, James AH, et al. von Willebrand disease (VWD): evidence-based diagnosis and management guidelines, the National Heart, Lung, and Blood Institute (NHLBI) Expert Panel report (USA). Haemophilia 2008; 14:171.
- Rodeghiero F, Castaman G, Tosetto A. How I treat von Willebrand disease. Blood 2009; 114:1158.
- Tosetto A, Castaman G. How I treat type 2 variant forms of von Willebrand disease. Blood 2015; 125:907.
- Tiede A, Rand JH, Budde U, et al. How I treat the acquired von Willebrand syndrome. Blood 2011; 117:6777.
- Ragni MV, Machin N, Malec LM, et al. Von Willebrand factor for menorrhagia: a survey and literature review. Haemophilia 2016; 22:397.
All topics are updated as new information becomes available. Our peer review process typically takes one to six weeks depending on the issue.