Von Willebrand disease

A common inherited bleeding disorder

Overview

Von Willebrand disease (VWD) is a genetic bleeding disorder caused by a deficiency or dysfunction of the von Willebrand factor (VWF), a protein that is crucial for blood clotting. It is the most common hereditary bleeding disorder in humans, affecting approximately 1% of the population. VWD is named after Erik Adolf von Willebrand, the Finnish physician who first described the condition in 1926.

Pathophysiology

Diagram showing autosomal dominant inheritance pattern.

Von Willebrand factor is a large multimeric glycoprotein that plays a key role in hemostasis. It mediates the adhesion of platelets to sites of vascular injury and stabilizes factor VIII, another important clotting protein. In VWD, the deficiency or dysfunction of VWF leads to impaired platelet adhesion and secondary deficiency of factor VIII, resulting in a bleeding tendency.

Types

VWD is classified into three main types based on the quantitative and qualitative defects of VWF:

Type 1

Type 1 VWD is the most common form, accounting for approximately 70-80% of all cases. It is characterized by a partial quantitative deficiency of VWF. Patients with type 1 VWD usually have mild to moderate bleeding symptoms.

Type 2

Type 2 VWD is a qualitative defect of VWF and is further divided into subtypes 2A, 2B, 2M, and 2N, each with distinct functional abnormalities of the VWF molecule. Type 2 VWD accounts for about 15-20% of cases.

Type 3

Diagram showing autosomal recessive inheritance pattern.

Type 3 VWD is the most severe form and is characterized by a near-complete absence of VWF. It is inherited in an autosomal recessive manner and is associated with severe bleeding episodes.

Pie chart showing relative incidences of VWD types.

Symptoms

The symptoms of VWD vary depending on the type and severity of the disease. Common symptoms include:

• Easy bruising
• Frequent nosebleeds
• Bleeding gums
• Heavy menstrual bleeding (menorrhagia)
• Prolonged bleeding from cuts
• Excessive bleeding after surgery or dental work

Diagnosis

The diagnosis of VWD involves a combination of clinical evaluation and laboratory tests. Key tests include:

• Measurement of VWF antigen levels
• VWF activity assays (e.g., ristocetin cofactor activity)
• Factor VIII activity
• Multimer analysis to assess the structure of VWF

Treatment

Treatment of VWD depends on the type and severity of the disease. Options include:

• Desmopressin (DDAVP), which stimulates the release of VWF from endothelial cells
• VWF replacement therapy using plasma-derived concentrates
• Antifibrinolytic agents such as tranexamic acid
• Hormonal therapy for menorrhagia

Prognosis

With appropriate management, individuals with VWD can lead normal lives. However, they may need to take precautions to avoid situations that could lead to bleeding.

Related pages

• Hemophilia
• Coagulation
• Platelet
• Factor VIII