From the Guidelines
Bernard Soulier Syndrome (BSS) is characterized by macrocytosis due to a genetic defect affecting the glycoprotein (GP) Ib-IX-V complex on platelet membranes, leading to abnormal platelet formation and release of large platelets into circulation. This condition presents with a classic diagnostic triad of giant platelets, thrombocytopenia, and prolonged bleeding time despite normal clotting factors 1. The genetic mutation in BSS disrupts normal platelet formation during megakaryocyte fragmentation in the bone marrow, resulting in the production of abnormally large platelets. Key features of BSS include:
- Macrocytosis (large platelets) due to altered platelet membrane structure and abnormal development
- Thrombocytopenia (low platelet count) resulting from impaired platelet production
- Prolonged bleeding time due to defective platelet adhesion to damaged blood vessels
- Normal clotting factors, distinguishing BSS from other bleeding disorders The diagnosis of BSS is often straightforward, as noted in the guidance from the SSC of the ISTH 1, but the diagnosis of other inherited platelet function disorders can be more complex and requires specialized assays.
From the Research
Bernard-Soulier Syndrome and Macrocytosis
- Bernard-Soulier syndrome (BSS) is a rare congenital platelet disorder characterized by defective platelet adhesion and manifested by spontaneous and often profuse bleeding 2.
- The syndrome is associated with macrothrombocytopenia, which is a condition characterized by low platelet count and abnormally large platelets 3.
- The macrothrombocytopenia in BSS is due to defects in the GPIb-IX-V complex, a platelet receptor for von Willebrand factor (VWF) 4.
- The GPIb-IX-V complex is composed of GPIbα, GPIbβ, and GPIX subunits, and mutations in the genes encoding these subunits can prevent expression of the complex at the platelet membrane or its interaction with VWF 4.
Clinical Features of Bernard-Soulier Syndrome
- Patients with BSS typically present with a moderate thrombocytopenia, giant platelets, and a bleeding tendency whose severity varies among individuals 5.
- The bleeding diathesis in BSS does not correlate with thrombocytopenia or platelet GPIbα expression, which is always severely impaired 5.
- Clinical features of BSS can include spontaneous bleeding, epistaxis, menorrhagia, and bleeding after trauma or surgery 2, 6.
Genetic Aspects of Bernard-Soulier Syndrome
- BSS is an autosomal recessive disorder, and most patients carry homozygous mutations in the GP1BA, GP1BB, or GP9 genes 4.
- There is a wide spectrum of mutations in BSS, with 112 different variants identified so far, including 22 novel alterations 4.
- The molecular basis of BSS is complex, and further investigations are needed to better understand the causes of this rare and underestimated disease 5, 4.