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Platelet glycoprotein IIb/IIIa antagonists have been shown in vitro to inhibit aggregation of human platelets stimulated with a wide variety of platelet agonists. To evaluate the in vivo effects of platelet glycoprotein IIb/IIIa antagonists on hemostasis, 6 baboons were pretreated with monoclonal antibody (MoAb) QBS-1 directed against the platelet glycoprotein IIb/IIIa complex. QBS-1 blocks all interactions of platelet glycoprotein IIb/IIIa with its substrates including fibrinogen and von Willebrand factor (vWf). After treatment, MoAb QBS-1 (50 micrograms/kg of body weight) or an equivalent volume of saline was administered intravenously. The baboons were then given three injections of either intravenous 30 mg/kg of the GP IIb/IIIa antagonist ReoPro or its placebo, or saline. Following ReoPro or placebo administration, the baboons received a 90 micrograms/kg injection of QBS-1 to block the effect of ReoPro and vice versa. The incidence of activated partial thromboplastin time (APTT) and activated clotting time (ACT) prolongation, as well as bleeding time (BT), were determined. We found that ReoPro induced a significantly prolonged BT following placebo or pretreatment with QBS-1 (59
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