What is Bernard-Soulier syndrome (BSS) platelet aggregation?

From the Guidelines

Bernard-Soulier syndrome (BSS) is characterized by abnormal platelet aggregation due to a deficiency or dysfunction of the glycoprotein Ib-IX-V complex on platelet surfaces, resulting in a failure to aggregate in response to ristocetin. In platelet aggregation testing for Bernard Soulier syndrome, platelets fail to aggregate in response to ristocetin, which normally binds to the GPIb-IX-V complex and von Willebrand factor to induce platelet clumping, as noted in studies on inherited platelet function disorders 1.

Key Characteristics of BSS

• The distinctive pattern of normal aggregation with other agonists (like ADP, collagen, and thrombin) but absent ristocetin-induced aggregation is diagnostic for the condition.
• The test is performed by adding ristocetin to platelet-rich plasma and measuring the aggregation response with a specialized aggregometer.
• Importantly, Bernard Soulier platelets are typically larger than normal (giant platelets) and present in reduced numbers (thrombocytopenia), as seen in patients with 22q11.2 deletion syndrome who may also have BSS 1.

Clinical Implications

• This aggregation defect occurs because the GPIb-IX-V complex serves as the primary receptor for von Willebrand factor, which is essential for platelet adhesion to damaged vessel walls, particularly under high shear stress conditions.
• The condition is inherited in an autosomal recessive pattern, meaning both parents must contribute a defective gene for the full syndrome to manifest.
• Careful management with attention to comorbid conditions and anatomical variants is crucial to mitigate increased risks and decrease fears associated with BSS and other bleeding disorders 1.

From the Research

Definition and Characteristics of Bernard-Soulier Syndrome (BSS)

• Bernard-Soulier syndrome (BSS) is a rare congenital platelet disorder characterized by defective platelet adhesion and manifested by spontaneous and often profuse bleeding 2.
• It is caused by mutations in the genes that encode the glycoprotein (GP) Ibα and GPIbβ subunits, as well as the GPIX subunit in the GPIbIX complex, which is located on the platelet surface and has roles in platelet adhesion and activation 3.
• Patients with BSS have variable thrombocytopenia and large defective platelets, and often present early with bleeding symptoms, such as epistaxis, ecchymosis, menometrorrhagia, and gingival or gastrointestinal bleeding 4.

Platelet Aggregation in BSS

• Platelet aggregation is impaired in BSS, with absence of ristocetin-induced platelet aggregation (RIPA) using light transmission aggregometry (LTA) in biallelic BSS 3.
• In monoallelic forms, the RIPA response in LTA may be decreased or normal 3.
• The impaired platelet aggregation is due to the defective GPIbIX complex, which is essential for platelet adhesion and activation 3.

Treatment and Management of BSS

• Platelet transfusion is the main therapy for BSS, but it should be used selectively and sparingly due to the risk of alloimmunization against HLA antigens and/or platelet glycoproteins 5.
• Recombinant factor VIIa (rFVIIa) is advised in alloimmunized patients, and allogeneic stem cell transplantation is suggested in refractory cases 3.
• Antifibrinolytics and oral contraceptives are utilized as supplementary treatments 5, 3.
• Desmopressin has been used in attempts to shorten bleeding times, but no definitive studies regarding its effectiveness have been reported 4.