Von Willebrand Disease (In Progress)

Summary

Von Willebrand Disease is an autosomal dominant bleeding disorder characterized by a deficiency of von Willebrand factor or vWF. This deficiency impairs platelet adherence to blood vessels, preventing the formation of a platelet plug to stop bleeding. Notably, vWF also carries and protects clotting factor 8, so when vWF is deficient, a decrease in circulating Factor 8 also occurs. Clinically, mild cases may be asymptomatic, but more severe cases exhibit signs of bleeding such as recurrent nosebleeds, petechiae in the skin, and easy bruising. Gastrointestinal bleeding and heavy menstrual bleeding may also occur.

The ristocetin lab test will reveal an abnormal result indicating impaired platelet aggregation. Notably, this abnormal ristocetin corrects with the addition of normal plasma, which happens because normal plasma contains vWF. PTT may be elevated, reflecting a decrease in circulating factor 8 levels. Bleeding Time is usually increased due to an impairment in platelet plug formation. Von Willebrand disease is usually treated with desmopressin, which works to stimulate the release of vWF from the walls of blood vessels.

Key Points

• Von Willebrand Disease (vWD)
  • Pathogenesis
    • Deficient von Willebrand Factor (vWF)
      • Impairs platelet adherence to blood vessels (primary hemostasis)
        • Since platelets bind to vWF released by endothelial cells to form the platelet plug
      • Decreases Factor VIII
        • vWF carries and protects factor VIII in the bloodstream
        • Causes bleeding due to defective intrinsic coagulation cascade
    • Note that vWF comes from Weibel-Palade bodies of endothelial cells and alpha-granules of platelets
  • Genetics
    • Autosomal dominant inheritance
    • More frequent in Caucasians
  • Presentation
    • Mucosal bleeding (oral, GI, uterine)
      • Epistaxis
      • Gingival bleeding
      • Petechiae
      • Easy bruising
      • Menorrhagia
  • Diagnosis
    • Ristocetin cofactor assay
      • Reduced ability of platelets to bind to ristocetin (artificial endothelial surface) is seen; no platelet aggregation
      • Corrects with addition of normal plasma containing vWF (contrast vs. Bernard-Soulier)
    • Normal or ↑ PTT
      • Due to decrease in active Factor VIII
    • Normal PT
      • Extrinsic coagulation pathway is unaffected
    • ↑ bleeding time
      • Unlike hemophilia, since platelet plug formation is impaired due to low vWF
    • CBC shows normal RBC and platelet count and appearance
      • Defect in quality of platelets, not quantity
  • Treatment
    • DDAVP (desmopressin)
      • Releases vWF stored in endothelial cells