Von Willebrand Disease

napshot

• A 25-year-old woman presents to the emergency room with prolonged bleeding after a dental procedure early that day. She has gone through several gauze packing with no success. Her past medical history includes heavy and prolonged menses. As a child, she had several episodes of unexplained nosebleeds. Labs show normal PT, PTT, and platelet count.

Introduction

• Inherited mixed platelet and coagulation disorder from deficiency in von Willebrand factor (vWF) 
• Genetics
  • autosomal dominant
• Epidemiology
  • most common inherited bleeding disorder
  • more likely in Caucasians
• Pathogenesis
  • affects coagulation – vWF carries and protects factor VIII 
    • produced by endothelial cells and megakaryocytes
    • intrinsic pathway coagulation defect 
  • affects platelets – vWF is important in platelet adherence to endothelial lining
• platelet aggregation is normal (mediated by fibrinogen)

Presentation

• Symptoms
  • mucocutaneous bleeding
    • epistaxis
    • gingival bleeding
    • petechiae
    • easy bruising
    • menorrhagia
• increased bleeding after aspirin use

Evaluation

• Normal or ↑ PTT (like hemophilia) 
• Normal PT
• ↑ bleeding time (unlike hemophilia)
• CBC
  • normal platelet count and appearance
  • may have anemia
• Diagnosis by ristocetin cofactor assay
  • tests ability of platelets to bind to ristocetin (artificial endothelial surface)
• ↓ platelet agglutination

Differential Diagnosis

• Bernard-Soulier syndrome 
• Glanzmann thrombasthenia 
• Hemophilia 

Treatment

• DDAVP (desmopressin acetate) 
  • releases vWF stored in endothelial cells
• Factor VIII replacement if refractory to DDAVP
• contains vWF

Prognosis, Prevention, and Complications

• Prognosis
  • most are mild or moderate in severity
• Prevention
  • avoid aspirin
• Complications
  • excessive bleeding