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 antithrombotic activity of aspirin and the murine monoclonal antibody P37, which inhibits platelet aggregation and fibrinogen binding to activated platelets.

BACKGROUND

The antithrombotic activity of P37 has been somewhat predictable, given its in vitro platelet antiaggregating activity and localization at or very near the fibrinogen binding site in the platelet fibrinogen receptor, the glycoprotein IIb/IIIa or integrin alpha IIb-beta 3.

METHODS

The monoclonal antibody P37 of the immunogamma-globulin-1 isotype was prepared according to previously described immunization and fusion protocols and screening assays. To compare its antiaggregating capacity with that of aspirin, experimental thrombosis was induced in all dogs by means of direct current applied to the carotid artery. Autologous platelets had previously been labeled with indium-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 thrombosis, and group III (n = 10) was treated intravenously with a single dose of P37 (0.8 mg/kg).

RESULTS

The indium-111 oxine activity deposited 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 differences between groups were always statistically significant (p < 0.05).

CONCLUSIONS

We conclude that a single dose (0.8 mg/kg) of P37 in a canine model of arterial thrombosis is approximately 100 times more efficient than the administration of aspirin (5 mg/kg per day) in preventing platelet deposition during thrombus formation.