Analysis of platelet aggregation disorders based on flow cytometric analysis of membrane glycoprotein IIb-IIIa with conformation-specific monoclonal antibodies. Blood

Normal primary platelet aggregation requires agonist-mediated activation of membrane GPllb-llla, binding of fibrinogen to GPllb-llla, and cellular events after ligand binding. PACl monoclonal antibody distinguishes between resting and activated states of GPllb-llla. and other anti-bodies preferentially recognize GPllb (PMI-1) or llla (anti-LlBSl) after the binding of fibrinogen or fibrinogen-mimetic peptides, such as GRGDSP. Using these antibodies and platelet flow cytometry, we studied two distinct persistent platelet aggregation abnormalities. Platelets from a throm-basthenic variant, which contained near-normal amounts of GPllb-llla. failed to aggregate or bind PACl in response to agonists. In addition, GRGDSP, which binds to normal GPllb-llla without prior cell activation, failed to increase the binding of PMI-1 or anti-LIBS1 to the thrombastheni