A variant of Glanzmann's thrombasthenia which fails to express a GPIIb-IIIa related epitope that is recognized by a specific monoclonal antibody (C17).
Binding of different antibodies to the GPIIb-IIIa complex in resting (AP2, EDU3, C17) or activated platelets (PAC1) was studied by flow cytometry in a patient with a platelet defect involving GPIIb-IIIa related functions. The patient has a mild history of bleeding. Aggregation induced by ADP and collagen were absent but normal response was obtained with ristocetin. Platelets from the patient do not bind fibrinogen. Perfusion studies with flowing blood showed that patient's platelets have a marked impairment in the process of spreading and aggregate formation on vascular subendothelium. Electrophoretic studies in SDS-polyacrylamide gels demonstrated the presence of normal amounts and normal mobility of GPIIb-IIIa. Fibrinogen was present in the patient's platelets (68-74% of controls). The binding of AP2 and EDU3 to patient's resting platelets was normal as assessed by flow cytometry. In contrast, a decreased presence of the C17 antigen (10 fold lower than control platelets) was detected in resting platelets and a markedly reduced binding of PAC1 was found in thrombin activated platelets. These studies suggest that C17 recognizes an epitope of the GPIIb-IIIa in resting platelets that is implicated in the regulation of adhesive and cohesive properties of GPIIb-IIIa. Studies on this patient might be helpful for the understanding of GPIIb-IIIa functions.
Escolar
G
G
Servicio de Hemoterapia y Hemostasia, Hospital Clínic i Provincial, Barcelona, Spain.
Diaz-Ricart
M
M
Garrido
M
M
Reverter
J C
JC
Villamor
N
N
Sanz
C
C
Maragall
S
S
Castillo
R
R
Ordinas
A
A
Nurden
A T
AT
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000276:immunology; D001095:Arachidonic Acids / Q000494:pharmacology; D003094:Collagen / Q000494:pharmacology; D000939:Epitopes / Q000276:immunology*; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects; D010980:Platelet Membrane Glycoproteins / Q000276:immunology*; D012310:Ristocetin / Q000494:pharmacology; D013915:Thrombasthenia / Q000097:blood / Q000276:immunology*
D000911:Antibodies, Monoclonal; D001095:Arachidonic Acids; D000939:Epitopes; D010980:Platelet Membrane Glycoproteins; D012310:Ristocetin; D000244:Adenosine Diphosphate; D005340:Fibrinogen; D003094:Collagen