GPIbIXVmangel

GPIbIXVMangel, sometimes written as GPIb-IX-V-Mangel, refers to deficiency of the platelet glycoprotein GPIb-IX-V receptor complex on the surface of circulating platelets. This deficiency disrupts the platelets' ability to bind von Willebrand factor and adhere to damaged endothelium, leading to a bleeding tendency with macrothrombocytopenia. The condition is most commonly associated with Bernard-Soulier syndrome, a rare inherited bleeding disorder.

The GPIb-IX-V complex comprises GPIbα (GP1BA), GPIbβ (GP1BB), GPIX (GP9), and GPV (GP5). It mediates platelet adhesion under high shear by binding von Willebrand factor; loss or dysfunction of any subunit reduces surface expression of the complex and impairs platelet function.

Genetically, GPIbIXV-mangel is typically inherited in an autosomal recessive manner. Mutations in GP1BA, GP1BB, GP9, or GP5 can reduce synthesis or assembly of the receptor, producing reduced GPIb-IX-V on platelets and the Bernard-Soulier phenotype.

Clinically, affected individuals present with mucocutaneous bleeding from early life, Epistaxis, easy bruising, and menorrhagia. Platelets are abnormally large (macrothrombocytopenia). Laboratory testing shows markedly decreased ristocetin-induced platelet aggregation that does not correct with normal plasma, and platelet flow cytometry demonstrates reduced GPIb-IX-V expression; von Willebrand factor activity and levels are typically normal or elevated.

Diagnosis relies on platelet function studies, flow cytometry for GPIb-IX-V, and genetic testing for GP1BA, GP1BB, GP9, or GP5 mutations. Management is supportive: antifibrinolytics for minor bleeds, platelet transfusions for significant bleeding or surgery, and avoidance of antiplatelet drugs; desmopressin may have limited efficacy.