One Percent of Americans Have Von Willebrand Disease

A hereditary bleeding disorder, von Willebrand disease (VWD) involves a protein in the blood called von Willebrand factor (VWF), which helps the blood to clot. People with VWD don't have enough of the factor available in their blood, or the VWF that is present doesn't function effectively. As a result, simple injuries can bring on heavier and longer bleeding episodes than usual or cause frequent bruises to form under the skin. The bleeding can damage internal organs or even be life threatening, although that is rare.

According to Joan Cox Gill, MD, Medical College of Wisconsin Professor of Pediatrics (Pediatric Hematology/Oncology/BMT), VWD affects men and women equally, and may be found in about 1% of the US population. There are three types or categories of the disease.

Type 1 is the most common, accounting for approximately 80% of those with VWD, Dr. Gill says. Patients may experience frequent nosebleeds, easy bruising, increased bleeding with tooth extraction or surgery, or experience heavy menstrual bleeding, known as menorrhagia. Affected patients may need to be treated for surgery or tooth extractions.

Type 2 VWD patients experience more significant bleeding symptoms; these patients tend to bleed more often and for longer periods of time, explains Dr. Gill . Symptoms, especially among children, include nosebleeds that occur more frequently and are more difficult to manage. Patients with Type 2 need to be treated during surgery or tooth extractions to prevent excessive bleeding. Women with Type 2 almost always experience menorrhagia. Some Type 2 patients even experience symptoms similar to mild hemophilia, she says.

Patients with Type 3 have no VWF and have low levels of Clotting Factor VIII (another important protein that helps the blood clot). Patients with Type 3 VWD experience severe bleeding symptoms, such as deep tissue bleeding and joint bleeding. This condition is similar to moderate hemophilia, Dr. Gill says.

Diagnosis and Treatment
Dr. Gill, who practices at the Children's Hospital of Wisconsin Hematology/Oncology Clinic, says that diagnosing VWD can be challenging for general practitioners because there are many reasons for bleeding incidents. The first step in diagnosis is a thorough review of the patient's medical history. In particular, the primary care physician will want to know more about any bleeding incidents: how often they occur, how severe they are, and how long they last. Family medical history is also explored, to see if VWD has been present. Although VWD is hereditary, symptoms can vary from one family member to another, and some family members might not even know they have the disease.

If VWD is suspected, the patient is provided a dose of the medication desmopressin to see how much the VWF increases in response. Desmopressin helps to increase the VWF levels. "If the patient can attain a von Willebrand factor level of over 40% or so," Dr. Gill says, "then they can use it [desmopressin] to treat usually routine kinds of bleeding like nosebleeds, menorrhagia, cuts, and things like that. If they get to 40% but not 100%, then we can use it for everything but major surgery and major bleeding. If they get to 100% we can use it for everything. Most patients with type 1 VWD have really excellent responses and can usually be carried through with only the desmopressin."

Desmopressin is available in an intravenous form and a nasal spray. The nasal spray, known by the trade name Stimate, is a very convenient form of treatment for those patients with serious nose bleeds or heavy menstrual bleeding. An added benefit, she says, is that desmopressin is synthetic, so there is no risk of transmitting viruses such as Hepatitis B or HIV.

Some Type 2 patients are able to use desmopressin for minor bleeding, Dr. Gill says, but for major surgery and incidents of major bleeding, the patients must be treated with VWF/Factor VIII concentrates. Type 3 patients do not respond at all to desmopressin, so they must be treated with the Factor VIII concentrates.

Made from purified blood plasma, the VWF/Factor VIII concentrates are processed so that any viruses are rendered inactive. Two of these concentrates are licensed for treatment of VWD. Known by their trade names Humate-P and Alphanate, the concentrates have been used for years to treat hemophilia, she says. Humate-P is licensed to treat urgent bleeding and for use during surgery, while Alphanate has been licensed for surgery but not for patients with Type 3 VWD.

"We've been using them for treatment of von Willebrand disease," Dr. Gill says, "because the only other product for treatment of von Willebrand patients who don't respond to the desmopressin is cryoprecipitate, which is a local blood bank product. That local blood bank product is not virus-inactivated." The VVWF/Factor VIII concentrates are the preferred treatment, she says, because they have been virus-inactivated and there is "virtually no risk" of transmitting Hepatitis B or HIV.

VWD Patients Lead Normal Lives
People with VWD can lead full, productive lives, Dr. Gill says. She discourages patients from playing heavy contact sports, such as wrestling, tack football, rugby, and boxing. But, baseball, soccer, and tennis, among other sports, are fine. "There are lots of things that people can do," she says.

"I always try to emphasize in the mild Type 1 patients that this is not something that should interfere with your ability to live a full life," she says, adding that VWD patients must remember to tell doctors they have VWD prior to any surgery or tooth extraction.

The Future of Von Willebrand Disease
Dr. Gill says one pharmaceutical company is developing a recombinant VWF. This would contain genetically engineered clotting factors, as opposed to components purified from human blood, so there is an increased measure of safety. The VWF is a fairly complicated molecule, which is why there are so many types of VWD, including four subtypes of Type 2. And while this new recombinant factor is a few years away, the first clinical trials are now in the planning stage. "We're all very excited about the possibility of having a recombinant product for von Willebrand disease as we do for hemophilia," she says.

Although there is no cure for VWD, Dr. Gill says there is hope on the horizon. "As we learn more about the recombinant molecule and how to get normal genes into people who don't have normal genes, like those with hemophilia and other genetic disorders, there eventually could be a gene therapy available for von Willebrand disease," she says.

Thomas R. Fuszard
HealthLink Contributing Writer

This article includes information from the National Institutes of Health and the US Food and Drug Administration.

MCW Health News presents up-to-date information on patient care and medical research by the physicians of the Medical College of Wisconsin.