Bernard-Soulier Syndrome

Summary

Bernard-Soulier disease is an autosomal recessive platelet disorder caused by a defect in the GpIb receptor on platelets. A defect in GpIb prevents platelet adhesion to von willebrand factor or vWF, which impairs platelet aggregation into a platelet plug. Clinically, patients present with bleeding, with mucosal bleeding from their gums, petechiae, and recurrent nosebleeds, also known as epistaxis.  On laboratory testing, patients will have an abnormal Ristocetin test, signifying a defect in the binding of GpIb to vWF. Notably, this ristocetin test does not correct with the addition of normal plasma, since normal plasma replenishes vWF, but does not contain any GpIb. Other laboratory results include an increased Bleeding Time, which signifies an increased time needed to form a platelet plug. Peripheral blood smears will reveal giant platelets.

Key Points

• Bernard-Soulier Syndrome
  • Cause
    • Defect in GpIb receptors
      • Defective glycoprotein receptor on platelet surface prevents platelet adhesion to vWF
      • This eventually blocks formation of platelet plug (see: Platelet Plug Formation)
  • Genetics
    • Autosomal recessive inheritance
  • Presentation
    • Bleeding
      • Mucosal bleeding, e.g. gingival bleeding, menorrhagia
      • Microhemorrhages, e.g. petechiae, epistaxis, easy bruising
  • Diagnosis
    • Abnormal ristocetin test
      • Ristocetin antibodies promote binding of GpIb with vWF, which causes platelet aggregation in normal patients
      • No aggregation of platelets occurs in Bernard-Soulier disease
      • Does not correct with addition of normal plasma
        • Since plasma contains vWF, but does not contain GpIb
        • Contrast vs. von Willebrand disease, where replacement of deficient vWF causes correction
    • Increased bleeding time (BT)
      • Due to defective primary hemostasis from inability to bind vWF
    • PT, PTT are generally unaffected
    • Giant platelets seen on peripheral smear
      • Normal or decreased platelet count
  • Treatment
    • Supportive
      • Avoid drugs that increase risk of bleeding
      • May require platelet transfusions during surgery