What Is Von Willebrand Disease?

Von Willebrand disease (VWD) is a disorder associated with bleeding more than usual. Individuals with VWD have low levels of or a defective von Willebrand factor (VWF), a vital protein in blood clotting.

VWD is nearly always inherited (passed down from parent to child) and lifelong. Even though most people are born with VWD, it's often not diagnosed until adulthood, as symptoms tend to be mild. Rarely. it can be acquired. In acquired cases, VWD will resolve when the underlying condition has been treated.

This article reviews what it means to have von Willebrand disease, including its cause, types, and symptoms, and how it's diagnosed and managed.

What Happens If You Have Von Willebrand Disease?

Von Willebrand disease prevents your blood from clotting correctly or quickly. Blood clots are "plugs" created by platelets (disc-shaped cell fragments) and various proteins at the site of blood vessel injury.

The impaired blood clotting process in VWD leads to excessive bleeding, manifesting as spontaneous nosebleeds, easy bruising, and/or heavy menstrual periods.

Longer-than-normal bleeding after a minor cut, dental procedure, surgery, or childbirth is also common in people with VWD. In some cases, anemia develops as a result of excessive bleeding.

Very rarely is the bleeding in VWD severe or life-threatening, such as when it affects internal organs like the stomach or intestines.

What Causes Von Willebrand Disease?

In most cases (the exception is acquired VWD), the disease is inherited, meaning a person is born with it.

Gene mutations (alteration in DNA sequencing) that cause either a deficiency of VWF or a malfunctioning VWF result in von Willebrand disease.

VWF has these main functions:

• Connects platelets to other platelets and to the lining of a blood vessel at the site of an injury
• Binds to and protects blood clotting factor VIII (factor 8)

In summary, a defective or deficient VWF causes bleeding by preventing platelets from forming a blood clot and/or by reducing blood-clotting factor VIII levels.

Von Willebrand Disease Types

There are three main types of von Willebrand disease, varying in severity and inheritance pattern.

Type 1

Type 1 affects approximately 85% of individuals with VWD in the United States. It is inherited in an autosomal dominant pattern.

Type 1 VWD is characterized by low blood levels of VWF either because the body does not produce enough VWF or because VWF is removed too quickly from the bloodstream.

Bleeding symptoms in type 1 VWD tend to be mild to moderate.

Type 2

Type 2 VWD occurs as a result of a defective VWF protein. Bleeding symptoms are generally more severe than they are with type 1 VWD.

Type 2 VWD is further divided into four subtypes. These subtypes differ by inheritance pattern (autosomal dominant versus recessive) and bleeding severity.

Knowing what subtype you are is essential for guiding treatment decisions.

The four type 2 subtypes are:

• In Type 2A, the structure and size of VWF are altered, impairing its ability to connect to platelets.
• In Type 2B, VWF binds spontaneously to platelets, even in the absence of blood vessel injury. This results in lower levels of platelets and VWF because the body removes them.
• In Type 2M, VWF cannot effectively attach to a specific protein on platelet surfaces.
• In Type 2N, VWF can connect to platelets but not to factor VIII. As such, the body removes factor VIII from the body.

Regarding inheritance patterns, Type 2B and 2M show autosomal dominant inheritance, and Type 2N shows autosomal recessive inheritance. Type 2A may be inherited as autosomal dominant or recessive.

Type 3

Type 3 is inherited in an autosomal recessive pattern and is the rarest type of VWD, occurring in less than 1% of cases in the United States.

Type 3 VWD is usually diagnosed early in life as a person produces virtually no VWF, resulting in severe bleeding symptoms.

Acquired

Acquired VWD occurs when a person has a deficiency of or dysfunctional VWF because of an underlying health condition—not because of inherited genetic changes.

Diseases known to lead to acquired VWD potentially include:

• Lymphoproliferative disorders like multiple myeloma or non-Hodgkin lymphoma
• Myeloproliferative disorders like polycythemia vera or chronic myeloid leukemia
• Certain heart valve diseases like aortic stenosis
• Certain autoimmune diseases like systemic lupus erythematosus (SLE)
• Hypothyroidism (low thyroid activity)

Many medications have also been linked to acquired VWD, such as the anti-seizure drug Depakote (valproic acid) and the antibiotic Cipro (ciprofloxacin).

Von Willebrand Symptoms

Symptoms of von Willebrand disease vary based on disease type, age, and whether a person menstruates.

The most common symptoms of von Willebrand disease in decreasing frequency include:

• Heavy or prolonged menstrual bleeding (previously called menorrhagia)
• Frequent and easy bruising (from minimal trauma)
• Bleeding in the throat and mouth
• Frequent or hard-to-stop nosebleeds
• Prolonged gum bleeding after a dental procedure
• Heavy or extended bleeding after surgery
• Excessive bleeding from a minor wound

Other symptoms (more common in type 3 VWD) include:

• Blood in the stool (hematochezia) from bleeding in the stomach or intestines
• Blood in the urine (hematuria) from bleeding within the kidneys or bladder
• Severe joint pain or swelling from bleeding into the joint space (hemarthrosis)
  
  

How Is Von Willebrand Disease Diagnosed?

There is no single test to diagnose von Willebrand disease. Instead, a healthcare provider considers a person's symptoms, their family history of bleeding, and the results of various blood tests.

These blood tests include:

• A complete blood count (CBC) shows the number of red and white blood cells and platelets in the bloodstream and hemoglobin concentration.
• VWF antigen measures the level of von Willebrand factor in the bloodstream.
• Factor VIII clotting activity measures the activity of factor VIII in the bloodstream.
• The ristocetin cofactor test (VWF:RCo) measures the activity of VWF or how well it is functioning.

In VWD type 1 (most common), the CBC is normal, except possibly for anemia, which would show up as low hemoglobin. There is a mild reduction in von Willebrand factor antigen and the VWF: Rco test. Factor VIII clotting activity is mildly decreased or normal.

Additional tests are performed to help define the VWD subtype. As an example, the von Willebrand factor multimer analysis measures the size and structure of VWF and is particularly useful for identifying vWD types 2A and 2B.

Von Willebrand Disease Treatment

The treatment of von Willebrand disease depends on the type, symptoms, and severity of bleeding.

Such treatments include:

• Desmopressin (DDAVP) is a medicine that temporarily (up to eight to 12 hours) increases von Willebrand factor and factor VIII levels in the bloodstream. Desmopressin does not work for everyone, so it requires testing beforehand.
• Antifibrinolytics, like Cyklokapron (tranexamic acid), are drugs that help reduce the breakdown of blood clots. They may be prescribed if a person with VWD has a dental/surgical procedure or for those with heavy menstrual bleeding.
• Factor replacement therapies may be prescribed for people with more severe VWD or mild types who don't respond to DDAVP. These infusions contain VWF, with or without factor VIII, and help prevent or stop bleeding episodes.
• Birth control pills or a progestin-released intrauterine device (IUD) may be used in addition to standard VWD treatments for heavy menstrual bleeding.

Treating acquired VWF entails managing the underlying condition or stopping the offending medication if applicable.

Can You Prevent Von Willebrand Disease?

You cannot prevent von Willebrand disease, as the disease is inherited in most cases. The good news is that while not preventable, the condition can be managed well.

When to Contact a Healthcare Provider

If you have a history of increased bleeding, especially nosebleeds, abnormal bruising, heavy or prolonged menstrual periods, or extended bleeding after dental procedures or childbirth, bring this to the attention of a healthcare provider.

A family history of VWD or other bleeding disorders suggestive of VWD is another reason for seeing a healthcare provider.

When seeing the healthcare provider, they may utilize a bleeding assessment tool (BAT) to determine whether you need blood testing for VWD.

One such tool was created by the International Society of Thrombosis and Haemostasis (ISTH). Consider reading through this tool before your appointment.

Summary

Von Willebrand disease (VWD) causes excessive bleeding due to a defective or reduced amount of von Willebrand factor, a protein involved in blood clotting. This bleeding disease is nearly always inherited and commonly linked to heavy or prolonged menstrual bleeding, spontaneous nosebleeds, easy bruising, and extended bleeding after a minor cut or childbirth.

The diagnosis of VWD requires reviewing symptoms with a healthcare provider and undergoing various blood tests. Even though VWD is not preventable or curable, it can be managed. Specific therapies depend on a person's VWD type (there are three main types) and bleeding symptoms and severity.