von Willebrand Disease

von Willebrand Disease (vWD) is the most common inherited bleeding disorder. It is an inherited disorder of von Willebrand factor (vWF), which is a protein found in the blood that is important in the process of blood clotting. It is inherited by both boys and girls but is more often diagnosed in girls.

vWF has two important jobs in the body. It helps platelets (a type of blood cell) stick to injured areas of blood vessels, to help form a “platelet plug,” on which a blood clot can be built. It also helps to maintain the levels of factor VIII (a clotting protein that also plays an important role in forming blood clots) in the blood.

Single strands of vWF are bound together in different-sized clusters of the protein called “multimers” that circulate in the blood. The larger multimers are the most important for helping platelets bind to injured blood vessels.

Types of von Willebrand Disease

There are different types of vWD, with each type having a different effect on the roles of vWF.

Type 1

This is by far the most common type of vWD. In this type, a person’s body is only able to produce a fraction of the normal amount of vWF. Because there is less vWF to do its job, a person’s platelets do not stick to damaged blood vessels as well as they should, which can lead to an increase in bruising or bleeding. If a child is only able to make a small amount of vWF, then their levels of factor VIII may be lower than normal as well, so their blood does not clot normally, which can also lead to increased bruising and bleeding.

Type 2

In this type, a person’s body can make good amounts of vWF, but there is some defect in the vWF that is made so that it does not work as well. There are different subtypes:

• Type 2A: There is a defect in vWF so that it cannot form the larger multimers, so that platelets do not bind to an injured blood vessel as well.
• Type 2B: There is a defect in vWF so that it actually binds to platelets too well, and both platelets and vWF are taken out of the blood stream faster than normal, leading to lower levels of both in the blood.
• Type 2M: Similar to type 2A, there is a defect in the structure of vWF, so that it does not bind platelets as well, even though normal amounts of the larger multimers are present.
• Type 2N: There is a defect in vWF so that the vWF can bind platelets normally, but it cannot bind factor VIII and maintain normal levels, so the child has lower than normal levels of factor VIII in their blood.

Type 3

As in type 1, the person’s body cannot make normal levels of vWF. However, in this type their body cannot make any vWF, so their platelets do not bind an injured blood vessel normally and their factor VIII levels in the blood are significantly lower than normal.

What Causes von Willebrand Disease?

A person inherits vWD from either one or both of their parents. Type 1 is an autosomal dominant disorder, meaning it is inherited from one parent. Type 3 is autosomal recessive, meaning a person must inherit one gene from each parent in order have the disorder.

How Is von Willebrand Disease Diagnosed?

vWD is diagnosed with a set of special blood tests that are typically performed because a child has some bleeding or bruising that is suspicious for a bleeding disorder and they have a family history of vWD. The common tests that are performed include:

• vW antigen: This test tells how much protein is in the person’s blood, not how well it works. People with type 1 vWD have mild to moderate decreases in the amount of vWD antigen in their blood, while people with type 3 have none.
• vW activity (also called ristocetin cofactor activity): This test tells how well the protein works. If a person has a lot of antigen, but not much activity, then they may have a functional problem (Type 2).
• Multimer analysis: This test tells how much of the different-sized multimers a person’s body makes. It is useful for diagnosing the type 2 variants.
• Factor VIII: Because the factor VIII levels can be affected in some types of vWD, the person’s levels are normally checked.

What Are the Symptoms of von Willebrand Disease?

The bleeding symptoms experienced are variable; they may be mild or severe and depend upon which function of vWF is affected. If children have a type in which platelet binding is affected, then they typically have mucocutaneous bleeding. This means they have bleeding involving the mucosal surfaces of the body, including nasal passages (nose bleeds), mouth (gum bleeding) and lining of the uterus (heavy or prolonged menstrual periods as they get older and bleeding after childbirth). They also can have cutaneous (skin) bleeding (more and bigger bruises than normal).

In those types in which factor VIII levels are lower than normal, the person can have bleeding into their deep soft tissues (large bruises that can be felt), and if the factor VIII levels are particularly low, they can have hemarthrosis (bleeding into the joints).

Some are unfortunate to have both defective platelet binding and low factor VIII levels (particularly those with type 3) and may experience many different bleeding symptoms.

People with the most common type of vWD, type 1, can have symptoms that range from relatively mild to severe. Many boys with type 1 vWD are not diagnosed, as their symptoms may be limited to bruising and nose bleeds. On the other hand, due to the common symptoms of heavy and prolonged periods as they mature, more young women than young men appear to be diagnosed with vWD.

How Is von Willebrand Disease Treated?

Fortunately, there are safe and effective treatments available for all types of vWD. They can be used either to treat bleeding episodes when they occur or prevent bleeding from planned surgeries, dental procedures or physical activities.

• von Willebrand factor/factor VIII concentrates: These are concentrated forms of both VWF and factor VIII which are made from donated blood or plasma. The substances undergo special steps to kill viruses of concern, such as HIV and hepatitis. People who require frequent infusions of factor concentrates can be trained to give them at home as needed.
• DDAVP: This is a synthetic form of a hormone found in the blood. It can be given as an injection into the vein or under the skin and there is a nasal spray form available well. People who make vWF usually have extra amounts stored in the body. DDAVP causes the body to release these extra stores into the blood. While DDAVP does not work for all people, most people with type 1 and some with type 2 can use DDAVP. Typically, patients are given a test dose by their physician to see if it works for them.
• Cryoprecipitate: This blood product is rich in both vWF and factor VIII that was used to treat vWD before factor concentrates were available. It is not a typical first choice for treatment of VWD, as it does not undergo viral inactivation as do factor concentrates and therefore may pose an infectious disease risk. However, when other treatments are not readily available for treatment of bleeding episodes, its use may be considered.