What are the characteristics of von Willebrand's (vWD) disease?

Characteristics of von Willebrand Disease

Von Willebrand disease (vWD) is an autosomal dominant inherited bleeding disorder characterized by deficiency or dysfunction of von Willebrand factor (VWF), with prolonged bleeding time, normal prothrombin time, and mucocutaneous bleeding rather than joint bleeding. 1

Inheritance and Prevalence

• vWD is the most common inherited bleeding disorder, affecting up to 1% of the general population 1, 2
• Males and females are affected in approximately equal proportions 1, 3
• Most cases (Type 1) are transmitted as an autosomal dominant trait with variable penetrance and expressivity 2

Pathophysiology

• vWD results from defects in von Willebrand factor (VWF), a multimeric plasma glycoprotein that:
  • Mediates platelet adhesion and aggregation at sites of vascular injury
  • Carries and stabilizes factor VIII (FVIII) in circulation 1, 3
• VWF is NOT synthesized in the liver (unlike most coagulation factors) but is produced by endothelial cells and megakaryocytes 4

Laboratory Findings

• Bleeding time: Typically prolonged (not normal) 1
• Prothrombin time (PT): Normal 3
• Activated partial thromboplastin time (aPTT): May be prolonged if factor VIII levels are reduced 1
• VWF antigen (VWF:Ag): Reduced in Types 1 and 3, may be normal or reduced in Type 2 5
• VWF activity (VWF:RCo): Reduced in all types 5
• Factor VIII levels: Often reduced due to decreased stabilization by VWF 1

Clinical Manifestations

• Primarily mucocutaneous bleeding (not joint bleeding) 1, 3:
  • Easy bruising
  • Nosebleeds (epistaxis)
  • Bleeding from minor wounds
  • Heavy menstrual bleeding (menorrhagia) in women
  • Gastrointestinal bleeding
  • Excessive bleeding after surgery, trauma, or childbirth
• Joint bleeding (hemarthrosis) is uncommon in most forms of vWD and is primarily seen in severe Type 3 vWD 6

Classification

1. Type 1 (75% of cases): Partial quantitative deficiency of VWF 1
2. Type 2 (qualitative deficiency): Functional defects in VWF 1
   • Subtypes: 2A, 2B, 2M, 2N
3. Type 3 (rare, ~1 in 1,000): Virtually complete quantitative deficiency 1

Common Pitfalls in Diagnosis

• Misdiagnosis is common due to:
  • Complex diagnostic requirements
  • Variability of bleeding symptoms
  • External variables affecting VWF levels (blood group, exercise, thyroid hormones, estrogens, aging) 3
  • Lack of disease awareness among non-specialist healthcare providers

Treatment Approaches

• Desmopressin (DDAVP): First-line therapy for most Type 1 patients; releases VWF from endothelial cells 6, 5
• VWF concentrates: For patients who don't respond to desmopressin or have Type 2 or 3 vWD 5
• Antifibrinolytics: Used as adjunctive therapy 5
• Hormonal therapy: For management of heavy menstrual bleeding in women 7, 5

Key Distinctions from Other Bleeding Disorders

• Unlike hemophilia, joint bleeding is not typically seen in vWD except in severe Type 3 cases 6
• vWD affects platelet function (primary hemostasis) in addition to potentially affecting factor VIII levels (secondary hemostasis) 1

The diagnosis of vWD requires specialized laboratory testing including VWF antigen levels, VWF activity assays, and multimer analysis, with molecular genetic testing sometimes needed for definitive classification 3, 5.