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Von Willebrand Disease (vWD)
Sunday, 27 July 2003
Monday, 04 December 2006
Pseudohemophilia, Vascular Hemophilia, Angiohemophilia

What

Von Willebrand disease (vWD) is the most common inherited bleeding disorder. It affects the ability of platelets (the cells which help in clotting) to stick to the vessels which are bleeding and form clots. vWD is inherited which means that changes in the genetic material that makes von Willebrand factor lead to the disease. Bleeding is prolonged after trauma or surgery, and symptoms such as nosebleeds or heavy menstruation can occur. There are different forms of vWD classified into types I, II, and III. Type I is most common, while type III is much more rare. Although vWD is a lifelong condition, many individuals with vWD are mildly affected so they may not even know that they have the disease. Others notice prolonged bleeding with menstruation or a history of easy bruising. Type III vWD is more severe and often has symptoms such as joint bleeding.

Who

vWD occurs equally in both males and females and occurs in all racial and ethnic groups. It has been found to affect about 1% to 3% of the population, with most affected people having Type I vWD (see “Possible Causes” below). Type II and III are much less common with Type III being the rarest, occurring in about one in a million people. Since vWD is a genetically-inherited disease, this implies that one or both of the parents also may be affected. People may have a large variation in the severity of bleeding and symptoms and may not know that they have the disease prior to their child being diagnosed. Normally, a person has a pair of genes that determines what characteristics that person has. In the case of Type I and Type II vWD, only one of the two genes in the pair needs to be affected. This is referred to as autosomal dominant. The other gene in the pair may be normal, but this child will still have vWD. In comparison, Type III vWD requires that both of the genes in the pair be affected (one from the mother and one from the father) which is known as autosomal recessive. This produces a disease, which has more severe bleeding.

Signs and Symptoms

Many individuals are unaware that they have vWD until they experience trauma or undergo surgery, which may be as routine as a tonsillectomy or having a tooth pulled. The severity of symptoms in vWD varies significantly with most people being only mildly to moderately affected. Symptoms in these cases can include easy bruising or bleeding such as with nosebleeds. The exception is individuals with Type III vWD who show more severe symptoms similar to those of a person with hemophilia such as bleeding into a joint. Any of the following symptoms may be present in a child with vWD: - frequent or prolonged nose bleeds; - easy bruising, often initially seen when the child begins crawling or walking; - bleeding of the gums; - heavy bleeding during menstruation which may lead to anemia; - prolonged bleeding after a cut, surgery including circumcision, or childbirth; - bleeding of the stomach or intestines.

Possible Causes

Normally when there is an injury, blood components known as platelets join together to patch the injury in the blood vessel and stop the bleeding. In order to strengthen this platelet patch, a special protein, known as fibrin, needs to be intertwined with the platelets. The platelet-fibrin mesh forms a clot, which functions to prevent bleeding and permit healing to occur. In order for this patching and clot formation to occur, a protein known as von Willebrand factor (vWF) is necessary. vWF assists platelets in sticking to injured blood vessels and helps to produce the fibrin needed for the blood clot. Additionally, vWF works as a carrier protein for Factor VIII, which is also needed for clot formation. In von Willebrand disease, vWF is either decreased in amount (Type I or Type III) or, although there may be normal amounts, is ineffective (Type II). Without vWF to carry Factor VIII, it is cleared from the circulation and results in a clinical picture similar to the severe, inherited bleeding disorder of hemophilia (also known as Factor VIII deficiency). Bleeding is prolonged and more likely to occur.

Diagnosis

Screening blood tests are often checked if a patient has bleeding or easy bruising. The tests will likely include a bleeding time, a platelet count, and a PTT (partial thromboplastin time). To do the bleeding time, a small cut is made on the arm, and the time it takes to stop bleeding is measured (infrequently used in smaller children). Blood will also be drawn to determine if the number of platelets is normal (low platelets can cause bleeding abnormalities). For the PTT test, blood is drawn and measured to determine how long it takes for the blood to clot. A child with vWD will have a normal platelet count but may show a prolonged PTT and/or bleeding time due to decreased or ineffective vWF, which is not allowing the blood to clot normally. However, even if the PTT and the bleeding time tests are normal, the child may still have vWD. Additional studies are performed to confirm whether or not a person has vWD. From a blood sample, the actual amount of vWF can be measured. Tests can also be performed to see how well the vWF is functioning, and depending on the abnormality in the vWF, the exact type of vWD (Type I, II or III) can be determined. Since the amount of vWF in the blood also affects the level of Factor VIII, this level may also be checked. It is important to realize though that the amount of vWF may be temporarily elevated if the person is stressed, such as with an illness, pregnancy or blood draw. There may also be variability depending on what the person’s blood type is, as people with O blood type normally tend to have lower levels of vWF.

Treatment

There are several different ways in which patients with vWD are treated. Patients with vWD are told to avoid aspirin and other drugs such as ibuprofen (non-steroidal anti-inflammatory drugs) because these may exacerbate bleeding problems by making the platelets less “sticky” when forming clots. For the majority of patients, no daily treatment is required for vWD. If a patient needs surgery or experiences an injury, treatments may be given to prevent or stop bleeding. For patients with Type I and some patients with Type II vWD with mild bleeding symptoms, desmopressin acetate (DDAVP) is the most commonly used therapy. This treatment increases the levels of vWF in the blood by causing its release from the patient’s blood vessels. In children less than two years old, DDAVP may not be as effective at releasing the vWF from the vessels. It can be given either intravenously (directly to a vein through a needle) or more commonly is given as a nasal spray called Stimate. Stimate is a more concentrated form of DDAVP (concentration 1.5mg/mL) compared to the less concentrated form used in the treatment of another medical condition known as diabetes insipidus, which does not cause increased release of vWF. A test dose of DDAVP is often given once a patient is diagnosed with vWD to determine how high vWF levels can be elevated with this medicine. Severe bleeding may require treatment with a Factor VIII replacement product, which also contains vWF. It is important to note that the recombinant Factor VIII products that are often used for treatment of hemophilia do not contain vWF and therefore cannot be used for treatment of patients with vWD. Cryoprecipitate is another blood product available in blood banks which contains vWF, but due to the potential, although minimal, risk of infection these tend not to be used. Even though these products are not routinely used, patients with vWD should still be sure to get immunized with Hepatitis A and B vaccines. Additional treatments can be used which are focused at stopping or preventing bleeding in the mouth, nose or with menstruation. For mouth or nose bleeding, there are medications which can be applied directly to the area to help with clot formation. Aminocaproic acid and tranexamic acid work to prevent a clot that has formed from dissolving, and oral contraceptive pills may also help minimize blood loss with menstruation.

Prognosis

Children with mild to moderate vWD are usually expected to have a normal life span. Some children with very mild symptoms (such as having only easy bruising) may never require any treatment, and those who do require therapy often respond well to those therapies mentioned above. Children with Type III vWD have more severe bleeding problems, and their prognosis is more variable. They should receive comprehensive care at a specialized treatment center. It is important that parents of children and the children themselves with known vWD tell health care professionals about their disorder so that they can receive proper treatment in the event of an accident or if surgery is to be performed. A med-alert bracelet with the diagnosis of vWD should be worn so that proper treatment can be initiated by emergency personnel. A physician may recommend that contact sports be avoided by individuals with more severe disease. Genetic counseling should be considered by an individual with vWD who plans to have a child, and it is also important for a woman with vWD to talk with her physician if she is pregnant to minimize the risk of severe bleeding during pregnancy and during delivery.

Connect with other parents

In the spirit of community and support, Madisons Foundation offers the unique service of connecting parents of children with rare diseases. If you would like to be connected to other parents of children with this disease, please fill out this brief form.

Weblinks

National Hemophilia Foundation Bleeding Disorders Information Center
An excellent overview of von Willebrand disease, organized similarly to the one above.

Kids Health for Parents

Kids Health for Teens
A website focused on pediatric patients with von Willebrand disease, which has information for both parents and teens.

National Heart, Lung, and Blood Institute
Provides a good explanation of clotting and the different clotting factors involved in von Willebrand disease.

Canadian Hemophilia Society
Clearly explains normal mechanisms of blood clotting and gives a basic overview of von Willebrand disease. Also, this website has several “personal stories” of people with von Willebrand disease and their families.

Google Search for Von Willebrand Disease (vWD)

References and Sources

Hambleton J (2001). “Diagnosis and incidence of inherited von Willebrand disease.” Current Opinion on Hematology, 8:306-311. Lane PA, Nuss R, Ambruso DR (2003). Chapter 27—“Hematologic Disorders,” section on “Von Willebrand Disease,” Current Pediatric Diagnosis & Treatment, 16th ed., online.statref.com/document.aspx?fxid=33&docid=461 Montgomery RR, Gill JC and Scott JP, Chapter 44—“Hemophilia and von Willebrand Disease,” Nathan and Oski’s Hematology of Infancy and Childhood 5th Edition., Editors: Nathan DG and Orkin SH. Rick ME (2005). “Classification and pathophysiology of von Willebrand disease.” UpToDate. Online: www.uptodate.com. Accessed on September 4, 2005. Rick ME (2005). “Clinical presentation and diagnosis of von Willebrand disease.” UpToDate. Online: www.uptodate.com. Accessed on September 4, 2005. Rick ME (2005). “Treatment of von Willebrand disease.” UpToDate. Online: www.uptodate.com. Accessed on September 4, 2005. White GC, Montgomery RR (2000). Chapter 114—“Clinical Aspects of and Therapy for von Willebrand Disease,” pp. 1946-1955, Hoffman: Hematology: Basic Principles and Practice, 3rd ed., home.mdconsult.com/das/book/29337711/view/1053/1110.html/top