Platelet Membrane Glycoproteins: A Historical Review

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Archivo: tromboembolia-venosa/tvp/STH 2014 Interference in Coagulation Testing.pdf

The search for the components of the platelet surface that mediate platelet adhesion andplateletaggregationbeganforearnestinthelate1960swhenelectronmicroscopy demonstrated the presence of a carbohydrate-rich, negatively charged outer coat that was called the “glycocalyx.” Progressively, electrophoretic procedures were developed that identified the major membrane glycoproteins (GP) that constitute this layer. Studies on inherited disorders of platelets then permitted the designation of the major effectors of platelet function. This began with the discovery in Paris that platelets of patientswithGlanzmannthrombasthenia,aninheriteddisorderofplateletaggregation, lackedtwomajorGP.Subsequent studiesestablishedthe rolefor the GPIIb-IIIacomplex (now known as integrin αIIbβ3) in bindingfibrinogen and other adhesive proteins on activated platelets and theformation of the protein bridges that join platelets together in the platelet aggregate. This was quickly followed by the observation that platelets of patients with the Bernard–Soulier syndrome, with macrothrombocytopenia and a distinctdisorderofplateletadhesion,lackedthecarbohydrate-rich,negativelycharged, GPIb. It was shown that GPIb, through its interaction with von Willebrand factor, mediated platelet attachment to injured sites in the vessel wall. What follows is a personal reflection on the studies that were performed in the early pioneering days.

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