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
M. Meyer et al., 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, Platelets, 7(4), 1996, pp. 215-224
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.