Von Willebrand disease

Von Willebrand disease is a bleeding disorder that slows the blood clotting process. People with this condition often experience bruising, nosebleeds, and prolonged bleeding or oozing following an injury, surgery, or having a tooth pulled. Women with this condition typically have excessive bleeding during menstruation (menorrhagia). In severe cases of von Willebrand disease, heavy bleeding occurs after minor trauma or even in the absence of injury (spontaneous bleeding). Milder forms of von Willebrand disease do not involve spontaneous bleeding, and the condition may become apparent only when abnormal bleeding occurs following surgery or a serious injury. Symptoms of von Willebrand disease may change over time. Increased age, pregnancy, exercise, and stress may cause von Willebrand factor levels to rise and bleeding symptoms may become less frequent.

Von Willebrand disease is divided into three types, with type 2 being further divided into four subtypes. All types of this condition cause prolonged bleeding episodes of varying severity; type 1 is the mildest of the three types and type 3 is the most severe. The four subtypes of type 2 von Willebrand disease are intermediate in severity. Another form of the disorder, acquired von Willebrand syndrome, is not caused by inherited gene mutations. Acquired von Willebrand syndrome is typically seen in conjunction with other disorders, such as diseases that affect bone marrow or immune cell function. This rare condition is characterized by abnormal bleeding into the skin and other soft tissues, usually beginning in adulthood.

The prevalence of von Willebrand disease is disputed. Some studies report a prevalence of 1 in 10,000, while other studies estimate the condition affects as many as 1 in 100 people. Most researchers agree that von Willebrand disease is the most common genetic bleeding disorder.

Mutations in the VWF gene cause von Willebrand disease. The VWF gene provides instructions for making a blood clotting protein called von Willebrand factor. Blood clotting proteins are essential for the formation of blood clots. After an injury, clots protect the body by sealing off damaged blood vessels and preventing further blood loss. If von Willebrand factor does not function normally or too little of the protein is available, blood clots cannot form properly. Abnormally slow blood clotting causes the prolonged bleeding episodes seen in von Willebrand disease.

Von Willebrand disease is broadly divided into three types based on von Willebrand factor levels. Mutations in the VWF gene that reduce the amount of von Willebrand factor cause type 1 von Willebrand disease. People with type 1 have varying amounts of von Willebrand factor in their bloodstream. Some people with a mild case of type 1 never experience a prolonged bleeding episode. Type 1 is the most common form of von Willebrand disease. Mutations that disrupt the function of von Willebrand factor cause the four subtypes of type 2 von Willebrand disease. People with type 2 von Willebrand disease have bleeding episodes of varying severity depending on the extent of von Willebrand factor dysfunction, but the bleeding episodes are typically similar to those seen in type 1. Mutations that result in an abnormally short, nonfunctional von Willebrand factor generally cause type 3 von Willebrand disease. People with type 3 typically have more severe bleeding episodes than those with type 1 or 2 von Willebrand disease. Type 3 is the rarest form of this condition.

Read more about the VWF gene.

Von Willebrand disease can have different inheritance patterns.

Type 1 and rare cases of type 2 von Willebrand disease are inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.

Type 3 and most cases of type 2 von Willebrand disease are inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. Most often, the parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but do not show signs and symptoms of the condition.