Bernard-Soulier Syndrome and Glanzmann thrombasthenia

Bernard-Soulier Syndrome

• Etiology/Pathophysiology
  • Autosomal Recessive deficiency of GpIb.
  • Impairs platelet Adhesion.
  • Platelets cannot bind to vWF on exposed subendothelial collagen.
  • Mnemonic: Bernard-Soulier = Big Suckers (Giant platelets) or Binds Surface (Adhesion).
• Clinical Features
  • Mucocutaneous bleeding (epistaxis, menorrhagia, gingival bleeding).
  • Petechiae, purpura, ecchymoses.
  • Post-surgical bleeding/trauma.
• Diagnostics
  • CBC: Mild to moderate Thrombocytopenia.
  • Peripheral Smear: Giant Platelets (Large platelets).
    • The GpIb-IX-V complex has two functions:
      • External: Binds to vWF (Adhesion).
      • Internal: Anchors the platelet membrane to the internal cytoskeleton (specifically Filamin A and actin).
    • In Bernard-Soulier, the lack of GpIb disrupts the membrane-cytoskeleton link.
    • The megakaryocyte cannot organize the cytoskeleton properly to pinch off small platelets.
    • Result: Instead of small fragments, large, immature chunks of cytoplasm break off, resulting in Giant Platelets (often approaching the size of RBCs).
  • Bleeding Time: ↑ (Prolonged).
  • Ristocetin Cofactor Assay: Abnormal (No agglutination).
    • Ristocetin activates vWF to bind GpIb; without GpIb, no clumping occurs.
    • Does NOT correct with the addition of normal plasma (which contains functional vWF) (distinguishes from von Willebrand Disease). t
• Treatment
  • Platelet transfusion (for severe bleeding).
  • Antifibrinolytics (e.g., tranexamic acid).

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Glanzmann Thrombasthenia

• Etiology/Pathophysiology
  • Autosomal Recessive deficiency of GpIIb/IIIa.
  • Impairs platelet Aggregation.
  • Platelets cannot bind Fibrinogen (which links platelets together).
  • Mnemonic: Glanzmann Aggregates (defect in aggregation).
• Clinical Features
  • Identical mucocutaneous bleeding pattern to Bernard-Soulier.
  • Petechiae, purpura, menorrhagia.
• Diagnostics
  • CBC: Normal platelet count.
  • Peripheral Smear: Normal platelet morphology; platelets appear isolated (no clumping).
  • Bleeding Time: ↑ (Prolonged).
  • Platelet Aggregation Studies:
    • Abnormal: No aggregation with ADP, Epinephrine, or Collagen.
    • Normal: Agglutination with Ristocetin (vWF-GpIb axis is intact).
• Treatment
  • Platelet transfusion (severe bleeding).
  • Recombinant Factor VIIa (refractory cases).

Feature	von Willebrand (vWD)	Bernard-Soulier (BSS)	Glanzmann (GT)
Defect	vWF deficiency	GpIb deficiency	GpIIb/IIIa deficiency
Mechanism	Impaired Adhesion	Impaired Adhesion	Impaired Aggregation
Platelets	Normal count/size	↓ Count, Giant size	Normal count/size
Ristocetin	Abnormal (Corrects w/ plasma)	Abnormal (No correction)	Normal
Key Diff	↑ PTT (maybe)	Big Platelets (“Big Suckers”)	No clumping (Abnormal ADP agg)