Inhibition of Human Platelet Function in Vivo with a Monoclonal Antibody

Abstract
The F(ab'')2 fragment of a monoclonal antibody to the platelet glycoprotein IIb/IIIa receptor (7E3) is a potent inhibitor or both in-vitro platelet aggregation and in-vivo platelet thrombus formation in animal studies. As a first step in assessing the potential of 7E3-F(ab'')2 as an antithrombotic agent for use in humans, we administered 7E3-F(ab'')2 intravenously at increasing doses to a person who had just died and was being maintained on a respirator (neomort). At 0.1 and at 0.2 mg/kg body weight, 74% and 92% of the glycoprotein IIb/IIIa receptors were blocked, respectively; adenosine-diphosphate-induced platelet aggregation was inhibited by 84% and 100% at these same doses. Platelet glycoprotein Ib function remained intact, even at 0.6 mg/kg. Acute hemodynamic or hemorrhagic toxicity was not noted. This antibody fragment, a potent, immediate-acting inhibitor of platelet aggregation, may be of benefit in vaso-occlusive and thromboembolic disorders.

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