Von Willebrand Disease Lecture Notes

Introduction

• Von Willebrand Disease (vWD): Most common inherited bleeding disorder.
• Affects about 1% of the population.
• Equally affects men and women.
• Inherited through autosomal dominant and recessive patterns.
• Caused by mutations in the von Willebrand factor (VWF) gene located on chromosome 12.

Function of Von Willebrand Factor (VWF)

• Hemostasis: Critical in platelet aggregation and adhesion.
• Platelet Receptor: Binds to glycoprotein 2b3a (GP2b3a) on platelets.
  • Facilitates platelet aggregation by binding multiple platelets.
• Additional Roles:
  • Acts as a chaperone for factor VIII.
  • Regulates angiogenesis.
  • Important in bone metabolism, inhibits rank L-induced osteoclastogenesis.

Von Willebrand Factor Structure

• Located in Weibel-Palade bodies in the endothelium.
• Released into circulation.
• Exists as multimers of varying sizes.
  • Larger multimers critical for platelet aggregation and adhesion.

Clinical Features of vWD

• Bleeding History: Generally mucocutaneous bleeds.
  • Gingival bleeds, epistaxis (nosebleeds), menorrhagia.
• Additional Features: Easy bruising, gastrointestinal bleeding, post-operative bleeding, immediate bleeding after trauma.
• Type 3 vWD: More severe with musculoskeletal bleeding.

Types of Von Willebrand Disease

• Type 1: Mild quantitative defect (80% of cases); autosomal dominant.
• Type 2: Qualitative/functional defect with subtypes:
  • 2A: Impaired multimerization.
  • 2B: Hyperfunctional platelet binding.
  • 2M: Decreased glycoprotein 1B binding.
  • 2N: Decreased factor VIII binding.
• Type 3: Severe, total quantitative defect; autosomal recessive.

Diagnosis

• Tests:
  • CBC for platelet count.
  • INR and PTT.
  • VWF activity and antigen levels.
  • Factor VIII levels.
  • Genetic testing.
• Blood Type Consideration:
  • Blood type O: Generally lower VWF levels.
  • Blood type AB: Higher VWF levels.

Treatment

• Desmopressin (DDAVP): For type 1 and 2A; stimulates release of VWF and factor VIII.
• Factor VIII Transfusion: For more severe cases.
• Blood Transfusion: For severe bleeds and anemia.

Acquired Von Willebrand Disease

• Causes:
  • Aortic stenosis, leading to shear stress on VWF.
  • Mechanical heart valves.
  • Wilms tumor.

• Conclusion: Understanding vWD is crucial for effective diagnosis and treatment, considering its prevalence and impact.