BernardSouliersyndroom

Bernard-Soulier syndrome, also referred to as Bernard-Souliersyndroom in some sources, is a rare inherited bleeding disorder characterized by macrothrombocytopenia and a defect in platelet adhesion due to deficiency of the platelet glycoprotein Ib-IX-V complex. It was described in 1948 by Bernard and Soulier and is inherited in an autosomal recessive pattern.

Pathophysiology and genetics: the condition results from mutations in the GP1BA, GP1BB, or GP9 genes, which encode subunits of the GP Ib-IX-V receptor. This receptor normally binds von Willebrand factor and mediates platelet adhesion to injured endothelium. Loss or dysfunction of the receptor leads to impaired platelet adhesion, reduced platelet counts, and enlarged platelets (macrothrombocytes).

Clinical features: individuals typically present with mucocutaneous bleeding from infancy, including epistaxis, gum bleeding, easy bruising, and menorrhagia. Bleeding severity is variable. Laboratory findings show thrombocytopenia with abnormally large platelets; ristocetin-induced platelet aggregation is markedly reduced and does not correct with the addition of normal plasma. von Willebrand factor levels are usually normal.

Diagnosis: suspected from a compatible bleeding history and family background. Confirmation is by specialized tests such as flow cytometry demonstrating absence or decreased expression of GP Ib-IX-V on platelets and genetic testing identifying mutations in GP1BA, GP1BB, or GP9. The ristocetin assay helps distinguish Bernard-Soulier syndrome from von Willebrand disease.

Management and prognosis: treatment focuses on bleeding prevention and timely management of crises. Avoidance of NSAIDs is advised. Antifibrinolytics (eg, tranexamic acid) can help mucosal bleeding; platelet transfusions are used for severe bleeds or perioperative care. Desmopressin is typically ineffective. With proper management, life expectancy is not markedly reduced, though bleeding risk persists.