von Willebrand disease Health Article

Demographics

Approximately 1 out of 100 people are affected with VWD, making it the most common inherited bleeding disorder (hemophilia). VWD affects people of all ethnic backgrounds. Approximately 70–80% of people with VWD have type 1 and close to 20–30% have type 2. Type 3 is very rare and occurs in less than one percent of people with VWD.

Signs and symptoms

VWD is usually a relatively mild disorder characterized by easy bruising, recurrent nosebleeds, heavy menstrual periods, and extended bleeding after surgeries and invasive dental work. There is a great deal of variability in the severity of symptoms, which can range from clinically insignificant to life threatening. Even people within the same family who are affected with the same type of VWD may exhibit different symptoms. An individual with VWD may exhibit a range of symptoms over the course of his or her lifetime and may experience an improvement in symptoms with age. The severity of the disease is partially related to the amount and type of vWF that the body produces, but is also influenced by other genetic and nongenetic factors.

Type 1

Type 1, the mildest form of VWD, is usually associated with easy bruising, recurrent nosebleeds, heavy menstrual periods, and prolonged bleeding after surgeries and invasive work. Many people with type 1 VWD do not have any noticeable symptoms or only have prolonged bleeding after surgery or significant trauma. The amount of vWF produced by the body increases during pregnancy, so prolonged bleeding during delivery is uncommon in people with type 1 VWD.

Type 2

People with type 2 VWD usually have symptoms from early childhood and symptoms may even be present at birth. They usually experience prolonged bleeding from cuts, easy bruising, nose bleeds, skin hematomas, and prolonged bleeding from the gums following teeth extraction and minor trauma. More than 50% of women with type 2 VWD experience heavy periods that may require a blood transfusion. Gastrointestinal bleeding is rare but can be life-threatening. Some women with type 2 VWD exhibit prolonged bleeding during delivery.

Type 3

Type 3 VWD can be quite severe and is associated with bruising and bleeding from the mouth, nose, intestinal, genital and urinary tracts. Type 3 is also associated with spontaneous bleeding into the muscles and joints, which can result in joint deformities. Some women with type 3 VWD experience prolonged bleeding during delivery.

Diagnostic testing

Many people with VWD have mild symptoms or symptoms that can be confused with other bleeding disorders making it difficult to diagnose VWD on the basis of clinical symptoms. VWD should be suspected in any person with a normal number of platelets in their blood and bleeding from the mucous membranes such as the nose, gums, and gastrointestinal tract. Testing for an individual with suspected VWD often includes the measurement of:

• how long it takes for the bleeding to stop after a tiny cut is made in the skin (the bleeding time)
• the amount of vWF (vWF antigen measurement)
• the activity of vWF (ristocetin co-factor activity)
• the amount of factor VIII (factor VIII antigen measurement)
• activity of factor VIII

People with type 1 VWD usually have an increased bleeding time but they may have an intermittently normal bleeding time. They also have a decreased amount of vWF, decreased vWF activity, and usually have slightly decreased factor VIII levels and activity. People with type 2 VWD have a prolonged bleeding time, decreased activity of vWF, and may have decreased amounts of vWF and factor VIII, and decreased factor VIII activity. Type 3 individuals have undetectable amounts of vWF, negligible vWF activity, factor VIII levels of less than 5–10%, and significantly reduced factor VIII activity. The activity of vWF is reduced for all types of VWD, making it the most sensitive means of identifying all three types of VWD. Patients with borderline results should be tested two to three times over a three month period.

Once a patient is diagnosed with VWD, further testing such as vWF multimer analysis and ristocetininduced platelet aggregation (RIPA) may need to be performed to determine the subtype. Multimer analysis evaluates the structure of the vWF, and RIPA measures how much ristocetin is required to cause the clumping of platelets in a blood sample. The vWF multimer analysis is able to differentiate people with a structurally normal vWF (type 1) from people with a structurally abnormal vWF (type 2) and is often able to identify the subtype of patients with type 2 VWD. People with type 1 VWD usually have normal to decreased RIPA concentrations. Depending on the subtype, patients with type 2 VWD either have increased or decreased RIPA. RIPA is usually absent and the multimer analysis shows undetectable vWF in people with type 3 VWD.

In some cases DNA testing can be a valuable adjunct to biochemical testing. The detection of gene alteration(s) can confirm a diagnosis and can determine the type and subtype of VWD. It can also help to facilitate prenatal testing and testing of other family members. Unfortunately, as of 2001, many people with VWD possess DNA changes that are not detectable through DNA testing. A person who has a mother, father, or sibling diagnosed with VWD should undergo biochemical testing for VWD. If the relative with VWD possesses a detectable gene change, then DNA testing should also be considered.