Bernard-Soulier syndrome

Bernard-Soulier syndrome (BSS), also known as giant platelet syndrome or hemorrhagiparous thrombocytic dystrophy, is a rare inherited bleeding disorder caused by a deficiency or dysfunction of the platelet glycoprotein Ib-IX-V complex (GPIb-IX-V). This complex serves as the primary receptor for von Willebrand factor (vWF) on the platelet surface and is essential for the initial adhesion of platelets to damaged blood vessel walls. Without a functional GPIb-IX-V complex, platelets cannot properly adhere to sites of vascular injury, leading to impaired primary hemostasis. The hallmark features of Bernard-Soulier syndrome include a lifelong bleeding tendency of variable severity, abnormally large platelets (macrothrombocytopenia), a reduced platelet count (thrombocytopenia), and prolonged bleeding time that is disproportionate to the degree of thrombocytopenia. Common clinical manifestations include easy bruising, epistaxis (nosebleeds), gingival (gum) bleeding, heavy or prolonged menstrual bleeding (menorrhagia) in affected women, and excessive bleeding following trauma or surgical procedures. Severe hemorrhagic episodes, including gastrointestinal bleeding, can occur. Symptoms typically present in infancy or early childhood, though the severity varies considerably even among members of the same family. Bernard-Soulier syndrome is caused by pathogenic variants in the GP1BA, GP1BB, or GP9 genes, which encode the GPIbα, GPIbβ, and GPIX subunits of the receptor complex, respectively. The classic form follows autosomal recessive inheritance, though a monoallelic (autosomal dominant) form with milder thrombocytopenia has been described. There is no cure for BSS. Management focuses on preventing and controlling bleeding episodes. Treatment strategies include local hemostatic measures, antifibrinolytic agents (such as tranexamic acid or aminocaproic acid), desmopressin (DDAVP) in some cases, and platelet transfusions for severe or life-threatening bleeding. Recombinant activated factor VII (rFVIIa) has been used as an alternative in refractory cases. Patients are advised to avoid antiplatelet medications and are counseled regarding surgical and dental precautions.

Common questions about Bernard-Soulier syndrome