Inhibition of human platelet function in vivo with a monoclonal antibody. With observations on the newly dead as experimental subjects.
The F(ab')2 fragment of a monoclonal antibody to the platelet glycoprotein IIb/IIIa receptor (7E3) is a potent inhibitor of 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.
State University of New York, Stony Brook.
B S
BS
Coller
L E
LE
Scudder
H J
HJ
Berger
J D
JD
Iuliucci
D000244:Adenosine Diphosphate / Q000037:antagonists & inhibitors; D000368:Aged; D000911:Antibodies, Monoclonal / Q000378:metabolism / Q000494:pharmacology*; D000918:Antibody Specificity; D001777:Blood Coagulation / Q000187:drug effects; D001792:Blood Platelets / Q000276:immunology*; D001926:Brain Death; D003094:Collagen / Q000037:antagonists & inhibitors; D028744:Ethics Committees, Research; D006805:Human Experimentation; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D010975:Platelet Aggregation Inhibitors; D010980:Platelet Membrane Glycoproteins / Q000276:immunology
D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D010975:Platelet Aggregation Inhibitors; D010980:Platelet Membrane Glycoproteins; D000244:Adenosine Diphosphate; D003094:Collagen