Is von Willebrand's disease (VWD) an autosomal dominant disorder?

Von Willebrand Disease: Key Characteristics

Von Willebrand disease (VWD) is an autosomal dominant disorder characterized by deficiency or dysfunction of von Willebrand factor (VWF), resulting in prolonged bleeding time, not prothrombin time.

Inheritance Pattern

Von Willebrand disease is primarily inherited as an autosomal dominant trait, particularly in Type 1 VWD which accounts for approximately 75% of all cases 1. This means that affected individuals typically have one parent with the condition, and each child has a 50% chance of inheriting the disorder.

While most cases follow autosomal dominant inheritance, it's important to note that:

• Type 3 VWD (the most severe form) typically follows autosomal recessive inheritance
• Some rare variants of Type 2 VWD may also demonstrate recessive inheritance patterns

Laboratory Findings

The key laboratory abnormalities in VWD include:

• Prolonged bleeding time - This is a characteristic finding in VWD due to impaired platelet adhesion at sites of vascular injury
• Normal prothrombin time (PT) - PT measures the extrinsic pathway of coagulation and is not affected by VWF deficiency
• Variable activated partial thromboplastin time (aPTT) - May be prolonged in severe cases due to secondary factor VIII deficiency

Pathophysiology

VWD results from qualitative or quantitative defects in von Willebrand factor, which has two primary functions:

1. Mediates platelet adhesion and aggregation at sites of vascular injury
2. Carries and stabilizes factor VIII in circulation 1

VWF is not synthesized in the liver but is produced by:

• Endothelial cells
• Megakaryocytes

Clinical Presentation

Patients with VWD typically present with:

• Easy bruising
• Mucosal bleeding (epistaxis, gingival bleeding)
• Gastrointestinal bleeding
• Heavy menstrual bleeding in women
• Prolonged bleeding after surgery, dental procedures, or trauma 1

The severity of symptoms varies widely, from mild bleeding in Type 1 to severe, potentially life-threatening bleeding in Type 3 VWD.

Classification

VWD is classified into three main types:

1. Type 1 (75% of cases): Partial quantitative deficiency of VWF
2. Type 2 (qualitative deficiency) with subtypes:
   • 2A: Decreased VWF-dependent platelet adhesion
   • 2B: Increased affinity for platelet glycoprotein Ib
   • 2M: Decreased platelet adhesion without loss of high molecular weight multimers
   • 2N: Decreased binding affinity for factor VIII
3. Type 3: Virtually complete absence of VWF (rare, affecting ~1 in 1,000)

Common Pitfalls in Diagnosis

• Mistaking VWD for other bleeding disorders due to overlapping symptoms
• Failure to recognize that VWD affects both primary hemostasis (platelet function) and secondary hemostasis (through factor VIII)
• Overlooking VWD in patients with mild bleeding symptoms
• Confusing laboratory values: remember that PT is normal while bleeding time is prolonged

In summary, von Willebrand disease is characterized by autosomal dominant inheritance (in most cases), prolonged bleeding time, normal prothrombin time, and is caused by deficiency or dysfunction of von Willebrand factor, which is not synthesized in the liver.