BASSET HOUND HEREDITARY THROMBOPATHY - AN INHERITED DISORDER WITH DEFECTIVE PLATELET-AGGREGATION DESPITE NORMAL FIBRINOGEN BINDING AND RECEPTOR MOBILITY

Basset Hound Hereditary Thrombopathy (BHT) resembles Glanzmann's throm basthenia having a primary aggregation abnormality and defective conta ct activation in plasma. It has been reported that, in suspension, act ivated BHT platelets bind fibrinogen normally. Therefore, the aggregat ion defect may be related to either an inability to mobilise ligand-oc cupied receptors or to an inability to initiate biochemical signal tra nsduction events following ligand binding. To investigate the former p ossibility we have used colloidal gold probes to examine the binding o f fibrinogen and the post-ligand binding reorganisation of fibrinogen receptors on adherent platelets. Adherent, spread BHT platelets were l abelled with either albumin-gold (AlbAu), fibrinogen-gold (Fg-Au) or F g-Au in the presence of physiological concentrations of unlabelled fib rinogen or specific glycoprotein (GP) IIb-IIIa inhibitors. Labelling o f fibrinogen receptors on BHT platelets was similar to control dogs an d humans. Binding was blocked by physiological concentrations of unlab elled fibrinogen as well as the arginine-glycine-aspartic acid-serine (RGDS) peptide and complex specific GP IIb-IIIa antibodies. Fibrinogen -gold binding was related to the stage of shape change, as early plate let dendritic forms demonstrated minimal gold binding that increased w ith more fully spread platelets. There was evidence of receptor redist ribution as well as movement of receptors into the open canalicular sy stem (OCS) following Fg-Au binding. In intermediate and spread platele ts the distribution was closely related to the orientation of the circ umferential microfilamentous system consistent with normal receptor-cy toskeletal interaction. Heavy labelling also occurred at points of pla telet-platelet interaction. In contrast to Glanzmann's thrombasthenia, BHT demonstrates normal fibrinogen binding to adherent platelets. Fur thermore, BHT platelets demonstrate normal receptor mobility and reorg anisation following ligand binding.