Abstract
Basset Hound Hereditary Thrombopathy (BHT) resembles Glanzmann's thrombasthenia having a primary aggregation abnormality and defective contact activation in plasma. It has been reported that, in suspension, activated BHT platelets bind fibrinogen normally. Therefore, the aggregation defect may be related to either an inability to mobilise ligand-occupied receptors or to an inability to initiate biochemical signal transduction events following ligand binding. To investigate the former possibility we have used colloidal gold probes to examine the binding of fibrinogen and the post-ligand binding reorganisation of fibrinogen receptors on adherent platelets. Adherent, spread BHT platelets were labelled with either albumin-gold (Alb-Au), fibrinogen−gold (Fg−Au) or Fg−Au in the presence of physiological concentrations of unlabelled fibrinogen or specific glycoprotein (GP) IIb−IIIa inhibitors. Labelling of fibrinogen receptors on BHT platelets was similar to control dogs and humans. Binding was blocked by physiological concentrations of unlabelled fibrinogen as well as the arginine-glycine-aspartic acidserine (RGDS) peptide and complex specific GP IIb−IIIa antibodies. Fibrinogen-gold binding was related to the stage of shape change, as early platelet dendritic forms demonstrated minimal gold binding that increased with more fully spread platelets. There was evidence of receptor redistribution as well as movement of receptors into the open canalicular system (OCS) following Fg−Au binding. In intermediate and spread platelets the distribution was closely related to the orientation of the circumferential microfilamentous system consistent with normal receptor-cytoskeletal interaction. Heavy labelling also occurred at points of platelet-platelet interaction. In contrast to Glanzmann's thrombasthenia, BHT demonstrates normal fibrinogen binding to adherent platelets. Furthermore, BHT platelets demonstrate normal receptor mobility and reorganisation following ligand binding.
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Estry, D.W., Mattson, J.C., Oesterle, J.R. et al. Basset Hound Hereditary Thrombopathy: An inherited disorder with defective platelet aggregation despite normal fibrinogen binding and receptor mobility. Comparative Haematology International 5, 227–236 (1995). https://doi.org/10.1007/BF02044139
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DOI: https://doi.org/10.1007/BF02044139