What is the characteristic of von Willebrand's disease (VWD)?

Characteristics of von Willebrand's Disease

Von Willebrand's disease (VWD) is an autosomal dominant bleeding disorder that does not result in prolonged prothrombin time, may cause thrombocytopenia only in specific subtypes, is associated with prolonged bleeding time, and can be treated with factor VIII therapy containing von Willebrand factor. 1

Inheritance Pattern

• VWD is predominantly inherited in an autosomal dominant pattern, particularly Type 1 (the most common form) and most Type 2 variants 1
• However, Type 3 VWD (the most severe form) and some rare variants may follow an autosomal recessive inheritance pattern 2

Laboratory Findings in VWD

Coagulation Tests

• Prothrombin Time (PT): Normal in VWD 3
  • VWD affects primary hemostasis and factor VIII levels but does not directly impact the extrinsic coagulation pathway measured by PT
• Activated Partial Thromboplastin Time (aPTT): May be prolonged in severe cases due to decreased factor VIII levels, but often normal in mild cases 3
• Bleeding Time: Typically prolonged in VWD due to impaired platelet adhesion at sites of vascular injury 4

Platelet Count

• Generally normal in most VWD types (Type 1, 2A, 2M, 2N, and Type 3) 1
• Thrombocytopenia may occur specifically in:
  • Type 2B VWD due to increased affinity of abnormal VWF for platelets, causing platelet aggregation and clearance 1
  • Platelet-type VWD (pseudo-VWD), which is often misdiagnosed as Type 2B 1

Treatment Approaches

Factor VIII Therapy

• Factor VIII concentrates containing VWF are the mainstay of treatment for moderate to severe VWD, especially Type 3 VWD 5
• These concentrates correct both the VWF deficiency and the secondary deficiency of factor VIII 6
• Long-term prophylaxis with VWF/FVIII concentrates is recommended for patients with severe bleeding phenotypes, typically at doses of 24 units FVIII/kg body weight, 1-3 times weekly 1

Desmopressin (DDAVP)

• Effective for mild Type 1 VWD and some Type 2 variants 5
• Stimulates the release of VWF from endothelial storage sites
• Administered at 0.3 μg/kg intravenously or subcutaneously 1
• Not effective in Type 3 VWD and contraindicated in Type 2B (may worsen thrombocytopenia) 1, 5

Clinical Pearls and Pitfalls

Diagnostic Challenges

• VWD is both under- and misdiagnosed, particularly milder forms 7
• Women appear more symptomatic than men with similar VWF levels, likely due to menstrual and childbirth-related bleeding 7
• Type 2B VWD can present as thrombocytopenia in infancy and may be misdiagnosed as immune thrombocytopenia 2

Treatment Considerations

• Baseline testing should include VWF:Ag, VWF:RCo, FVIII levels, complete blood count, and coagulation profile 1
• Treatment choice depends on VWD subtype - using the wrong treatment (e.g., DDAVP in Type 2B) can worsen the condition 1
• For surgical procedures, treatment should be initiated 30 minutes prior to the scheduled procedure 5

Special Populations

• Women with VWD may require additional management for menorrhagia and childbirth-related bleeding 6
• Hormone replacement therapy may be beneficial for some women with VWD but requires careful monitoring 1

VWD is a complex bleeding disorder with variable clinical presentations depending on the subtype. Accurate diagnosis through specialized laboratory testing is essential for appropriate management and prevention of bleeding complications.