A NEW VARIANT OF GLANZMANNS-THROMBASTHENIA WITH DEFECTIVE ACTIVATION-DEPENDENT FIBRINOGEN BINDING AND ALTERED EXPRESSION OF EPITOPES FOR SEVERAL MONOCLONAL-ANTIBODIES AGAINST GP IIB-IIIA

In a family, a moderate bleeding disorder in two patients has been spe cified as Glanzmann's thrombasthenia because of characteristic defects in platelet function, Analysis of platelet membrane glycoproteins rev ealed about a 50% decrease in the amount of GP IIb-IIIa complex (alpha (IIb)beta(3) integrin), which appeared normal with respect to electrop horetic mobility, apparent M(r) and isoelectric behaviour of GP IIb an d GP IIIa. Content of platelet fibrinogen (Fg) was normal, [I-125]Fg b inding to ADP-stimulated platelets was strongly reduced but K-d values indicated a much higher affinity of the residual receptors for both [ I-125]Fg and RGD peptide, Fg bound to the isolated complex as detected by crossed immunoelectrophoresis and there was substantial expression of endogenous Fg on the surface of washed thrombin-stimulated platele ts, RGD-peptide induced increased binding of conformation-specific mon oclonal antibodies (Mabs) LIES 1 and PMI-1, Flow cytometric analysis r evealed defective binding of nine Mabs, among them two out of three te sted antibodies specific for GP IIIa (C 17, AP 5), Results indicate a genetic variant of GP IIb-IIIa complex with the structural abnormality possibly related to defective conformational change upon activation.