A murine monoclonal antibody that completely blocks the binding offibrinogen to platelets, produces a thrombasthenic-like state in normal platelets and binds to glycoproteins Ilb and/or IIIa

ogen receptor in platelet physiology and to character-ize it biochemically, a murine monoclonal antibody that completely blocks the binding of fibrinogen to the platelet surface was produced by the hybridoma tech-nique with the aid of a functional screening assay. Purified F(ab')2 fragments and/or intact antibody com-pletely blocked aggregation induced by ADP, throm-bin, or epinephrine and the binding of radiolabeled fibrinogen to platelets induced by ADP. The antibody did not block agglutination of formaldehyde-fixed platelets by ristocetin or shape change induced by ei-ther ADP or thrombin. ADP- and epinephrine-induced release of ATP was completely inhibited by the anti-body, but inhibition of release induced by collagen and thrombin was dose dependent and partial. The antibody also dramatically inhibited platelet retention in glass-bead columns, platelet adhesion to glass, and clot retraction. Thus, the antibody induced a throm-basthenic-like state. Immunofluorescent studies con-firmed the specificity of the antibody for normal plate-lets and megakaryocytes and suggested that there is a marked decrease in detectable antigen in thrombas-thenic platelets. Radiolabeled antibody bound to an average of-40,000 sites on normal platelets but it bound to <2,000 sites on the platelets of a patient with thrombasthenia. The antibody immunoprecipitated both glycoproteins IIb and IlIa, and both glycoproteins bound to an affinity column of the antibody. Thes