Bernard-Soulier disease (giant platelet syndrome, benign Mediterranean macrothrombocytopenia)

Etiology

deficiency in platelet glycoprotein Ib/IX

Epidemiology

• rare disorder
• more common in whites & blacks

Pathology

• congenital platelet defects
• decreased platelet adhesion
• platelets cannot bind von Willebrand factor (vWF)

Genetics

• autosomal dominant (benign Mediterranean macrothrombocytopenia)
• recessive inheritance
• associated with defects in platelet GP-1b-alpha (GP1BA, CD42a)
• associated with defects in platelet GP-1b-beta (GP1Bb, CD42b)

Clinical manifestations

• moderate to severe bleeding with surgery & menstruation
• bleeding generally occurs from:
  • mucous membranes
  • gums
  • gastrointestinal tract
• autosomal dominant form (benign Mediterranean macrothrombocytopenia)
  • mild or no clinical symptoms

Laboratory

• thrombocytopenia with giant platelets
• bleeding time is markedly prolonged
• platelet aggregation
  • opposite to that of Glanzmann's thrombasthenia
  • normal response to ADP, collagen, epinephrine & thrombin
  • no aggregation with ristocetin
• normal levels of von Willebrand factor (vWF)
• autosomal dominant form (benign Mediterranean macrothrombocytopenia)
  • normal platelet function
  • normal megakaryocyte count in bone marrow biopsy

Management

• platelet transfusions for active bleeding as needed
• epsilon-aminocaproic acid for active bleeding as needed

More general terms

• platelet disorder; thromboasthenia

Additional terms

• platelet glycoprotein 1b
• von Willebrand factor; vWF; ristocetin cofactor; factor VIII related antigen; contains: von Willebrand antigen 2 (VWF, F8VWF)

Database

• OMIM: https://mirror.omim.org/entry/231200
• OMIM: https://mirror.omim.org/entry/153670