Von Willebrand's Disease

Definition | Aetiology | Pathophysiology | Risk Factors | Signs and Symptoms | Investigations | Management

Definition

Von Willebrand's disease (VWD) is an inherited bleeding disorder caused by a deficiency or dysfunction of von Willebrand factor (VWF), leading to impaired platelet adhesion and coagulation.

Aetiology

  • Type 1 VWD: partial quantitative deficiency of VWF (most common).
  • Type 2 VWD: qualitative defects in VWF function.
  • Type 3 VWD: severe deficiency or absence of VWF (rarest and most severe).
  • Acquired VWD: associated with autoimmune conditions, malignancies, or cardiovascular disease.

Pathophysiology

  • VWF plays a key role in platelet adhesion to damaged endothelium.
  • It stabilises factor VIII, prolonging its half-life.
  • Deficiency or dysfunction leads to impaired primary haemostasis and prolonged bleeding.

Risk Factors

  • Family history of bleeding disorders.
  • Autosomal inheritance (dominant in types 1 and 2, recessive in type 3).
  • Associated conditions (e.g., hypothyroidism, autoimmune disorders in acquired VWD).

Signs and Symptoms

  • Easy bruising.
  • Prolonged bleeding after minor cuts or surgery.
  • Epistaxis (frequent nosebleeds).
  • Menorrhagia in females.
  • Gastrointestinal bleeding in severe cases.
  • Haemarthrosis and deep tissue bleeding (more common in type 3 VWD).

Investigations

  • Full blood count (FBC): usually normal, may show mild anaemia.
  • Coagulation tests: normal PT, prolonged APTT in some cases.
  • Von Willebrand factor antigen: quantifies VWF levels.
  • Ristocetin cofactor activity: assesses VWF function.
  • Factor VIII activity: may be reduced due to VWF stabilisation role.
  • Genetic testing: confirms diagnosis in uncertain cases.

Management

1. General Measures:

  • Avoid NSAIDs and aspirin (increase bleeding risk).
  • Use antifibrinolytics (tranexamic acid) for minor bleeding.

2. Specific Treatment:

  • Desmopressin (DDAVP): increases endogenous VWF release (effective in type 1).
  • VWF replacement therapy: for type 2 and 3 VWD or major bleeding.
  • Factor VIII concentrates: if factor VIII levels are significantly reduced.

3. Referral:

  • Haematology: for diagnosis and long-term management.
  • Obstetrics/gynaecology: if menorrhagia is severe.
  • Surgical teams: for perioperative planning in affected patients.
HaematologymypanotesVon Willebrand's Disease