Von Willebrand Disease — causes, types and symptoms

What is von Willebrand disease

Von Willebrand disease (VWD) is a bleeding disorder. People with VWD have a problem with a protein in their blood called von Willebrand factor (VWF) that helps control bleeding. They do not have enough of the protein or it does not work the way it should. It takes longer for blood to clot and for bleeding to stop.

VWD is the most common inherited bleeding disorder. It affects both males and females. VWD is generally less severe than other bleeding disorders. Many people with VWD may not know that they have the disorder because their bleeding symptoms are very mild. For most people with VWD, the disorder causes little or no disruption to their lives except when there is a serious injury or need for surgery. However, with all forms of VWD, there can be bleeding problems.

It is estimated that up to 1% of the world's population has VWD, but because many people have only very mild symptoms, only a small number of them know they have it. In the Czech Republic, the CNHP registry has 701 people with VWD registered (an estimated 1,000 symptomatic patients in total). Research has shown that as many as 9 out of 10 people with VWD have not been diagnosed.

History of discovery

VWF is named after Finnish physician Erik von Willebrand (1870–1949), who in 1926 first described a hereditary bleeding disorder in families on the Åland Islands, where he observed a tendency to bleed into the skin, from mucous membranes and heavy menstrual bleeding. Although he could not identify the cause, he distinguished VWD from haemophilia and other forms of bleeding disorders.

In the 1950s, it was shown that VWD is caused by a deficiency of a plasma factor, and in the 1970s the VWF protein was isolated.

Inheritance and types

Von Willebrand disease affects men and women equally. Inheritance is usually autosomal dominant. In some types, inheritance is autosomal recessive, where an individual may carry the disease without external bleeding symptoms. According to the nature and severity of the disorder, VWD is divided into three types. Most cases are very mild with minimal impact on the patient. Severe, clinically significant forms are less common.

Type I

Approximately 75% of cases are Type I. This involves a partial quantitative deficiency of von Willebrand factor, and bleeding symptoms tend to be mild to moderate.

Type II

Type II accounts for approximately 47% of diagnosed cases in the Czech Republic according to the CNHP registry, and includes several subtypes (2A, 2B, 2M, 2N). In Type II, von Willebrand factor is present in normal or reduced amounts but is qualitatively altered — it does not function properly. Bleeding symptoms tend to be moderate. Diagnosis and treatment differ by subtype; for example, desmopressin is contraindicated in Type 2B.

Type III

Type III manifests as severely as or worse than severe haemophilia A. With significant reduction of VWF, there is a secondary decrease in FVIII. This results in bleeding into joints and muscles requiring intensive replacement therapy including prophylaxis. A concentrate with high von Willebrand factor content is therefore the ideal treatment of choice for such patients. Patients with clinically severe disease can, like people with haemophilia, also be treated prophylactically.

Care for patients with severe forms

People with severe forms of von Willebrand disease are currently in the care of haematologists and other medical specialists, and their care belongs in haemophilia centres. As with severe forms of haemophilia, prophylactic treatment (regular administration of medications to prevent bleeding) is essential for paediatric patients with significant VWF deficiency, preventing bleeding episodes and enabling normal physical growth and development.

Further information

• Von Willebrand disease treatment
• What is haemophilia — a related bleeding disorder
• Haemophilia treatment