PREVENTION OF ARTERIAL THROMBOSIS BY A MONOCLONAL-ANTIBODY AGAINST THE 100 TO 109 AMINO-ACID-SEQUENCE STRETCH OF THE BETA-SUBUNIT OF THE HUMAN PLATELET FIBRINOGEN RECEPTOR - A COMPARATIVE-STUDY WITH LOW-DOSE ASPIRIN

Objectives. The aim of this study was to compare, in dogs, the antithr ombotic activity of aspirin and the murine monoclonal antibody P37, wh ich inhibits platelet aggregation and fibrinogen binding to activated platelets. Background. The antithrombotic activity of P37 has been som ewhat predictable, given its in vitro platelet antiaggregating activit y and localization at or very near the fibrinogen binding site in the platelet fibrinogen receptor, the glycoprotein IIb/IIIa or integrin al phaIIb-beta(3). Methods. The monoclonal antibody P37 of the immunogamm aglobulin-1 isotype was prepared according to previously described imm unization and fusion protocols and screening assays. To compare its an tiaggregating capacity with that of aspirin, experimental thrombosis w as induced in all dogs by means of direct current applied to the carot id artery. Autologous platelets had previously been labeled with indiu m 111 oxine. The dogs were assigned to three groups: group I (n = 18) was the control group; group II (n = 12) was treated orally with 5 mg of aspirin/kg body weight per day for 7 days before induction of throm bosis, and group III (n = 10) was treated intravenously with a single dose of P37 (0.8 mg/kg). Results. The indium-111 oxine activity deposi ted in the thrombi was 12.94 +/- 12.83% (mean +/- SD) in group I, 3.55 +/- 2.99% in group II and 0.03 +/- 0.03% in group III. The difference s between groups were always statistically significant (p < 0.05). Con clusions, We conclude that a single dose (0.8 mg/kg) of P37 in a canin e model of arterial thrombosis is similar to 100 times more efficient than the administration of aspirin (5 mg/kg per day) in preventing pla telet deposition during thrombus formation.