Effects of Monoclonal Antibody Against the Platelet Glycoprotein IIb/IIIa Complex on Monkey Platelet In Vivo

Abstract

To assess the effects of a monoclonal antibody against the human platelet glycoprotein (GP) IIb/IIIa complex in vivo, the murien monoclonal antibody NNKY 1-32 was injected into Japanese monkeys.All of the IgG, F(ab′)2 and Fab fragments of NNKY 1-32 completely inhibited monkey platelet aggregation induced by ADP or collagen in vitro.Four monkeys received 0.4 and 1.0mg/kg of NNKY 1-32 F(ab′)2 or Fab fragments, while another four received 0.4mg/kg of NNKY 1-32 IgG fragments. In two monkeys given the IgG fragments of the antibody, platelet counts decreased remarkably. And in two other monkeys, transient thrombocytopenia was observed. In all monkeys, bleeding time was prolonged, platelet aggregation was suppressed, and the antibodies were associated with the platelets for up to 72 hours. Compared with the Fab fragments of the antibody, the F(ab′)2 fragments strongly suppressed platelet function. In general, the time course and dose-dependence of the effects of the injected antibodies were correlated with bleeding time, platelet aggregation and platelet-bound antibody titers.This study indicated that a murine monoclonal antibody that inhibits platelet aggregation in vitro could suppress platelet function in vivo without inducing spontaneous hemorrhage or marked thrombocytopenia.