A new variant of Glanzmann's 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 specified as Glanzmann's thrombasthenia because of characteristic defects in platelet function. Analysis of platelet membrane glycoproteins revealed about a 50% decrease in the amount of GP IIb-IIIa complex (α(11b)β(3) integrin), which appeared normal with respect to electrophoretic mobility, apparent M, and isoelectric behaviour of GP IIb and GP IIIa. Content of platelet fibrinogen (Fg) was normal. [(125)I]Fg binding to ADP-stimulated platelets was strongly reduced but K(d) values indicated a much higher affinity of the residual receptors for both [(125)I]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 platelets. RGD-peptide induced increased binding of conformation-specific monoclonal antibodies (Mabs) LIBS 1 and PMI-1. Flow cytometric analysis revealed defective binding of nine Mabs, among them two out of three tested 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.
Institut für vaskulär Biologie and Medizin. Erfurt; B. Jablonka, M. Just, Casella AG, Frankfurt/M.; C. M. Kirchmaier, Red Cross Blood Transfusion Service Hessen, J.W. Goethe University Frankfurt/M, Germany.
M
M
Meyer
A
A
Thieme
B
B
Jablonka
M
M
Just
C
C
Ströhl
I
I
Schellenberg
C M
CM
Kirchmaier