Abstract / Summary
Bernard–Soulier syndrome (BSS) is a rare inherited platelet disorder characterized by impaired platelet adhesion and defective primary hemostasis. It belongs to the group of inherited platelet function disorders and is associated with a variable bleeding phenotype, ranging from mild mucocutaneous bleeding to severe and potentially life-threatening hemorrhagic complications. BSS is most commonly inherited in an autosomal recessive manner and is caused by pathogenic variants affecting the genes encoding the components of the platelet glycoprotein GPIb-IX-V complex. The most frequently involved genes are GP1BA, GP1BB, and GP9, which encode the GPIbα, GPIbβ, and GPIX subunits, respectively. The GPIb-IX-V complex is an essential receptor on the platelet surface that mediates the interaction between platelets and von Willebrand factor (vWF), particularly under conditions of high shear stress. Under physiological conditions, vascular injury exposes subendothelial structures and promotes the binding of vWF to the damaged vessel wall. The subsequent interaction between vWF and the GPIb-IX-V complex on the platelet surface initiates platelet adhesion and activation. This process represents an essential early step in the formation of the primary platelet plug. In BSS, quantitative deficiency or structural abnormalities of the GPIb-IX-V complex impair platelet adhesion to the site of vascular injury, resulting in defective primary hemostasis and increased bleeding tendency. The clinical manifestations of BSS are predominantly related to mucocutaneous bleeding. Patients may present with recurrent epistaxis, gingival bleeding, easy bruising, petechiae, prolonged bleeding following dental procedures or surgery, and heavy menstrual bleeding. The severity of bleeding varies considerably between individuals. In severe cases, gastrointestinal, genitourinary, or other major bleeding may occur and can require urgent medical intervention. A characteristic hematological feature of BSS is the combination of thrombocytopenia and abnormally large, often giant, platelets. This morphological finding can provide an important diagnostic clue but may also complicate automated platelet counting because very large platelets can be incorrectly classified by some hematological analyzers.