Interruption of vascular thrombosis by bolus anti-platelet glycoprotein IIb/IIIa monoclonal antibodies in baboons

William C. Krupski, Arie Bass, Andrew B. Kelly, Zaverio M. Ruggeri, Laurence A. Harker, Stephen R. Hanson

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: Because the platelet membrane receptor glycoprotein IIb/IIIa plays a central role in the recruitment of platelets into forming thrombus, therapeutic inhibition of this receptor complex may be particularly useful to prevent thrombosis after small vessel arterial manipulation. Methods: The relative hemostatic safety and antithrombotic efficacy for thrombus formation at sites of endarterectomy and implanted prosthetic vascular graft of a murine monoclonal antibody (LJ-CP8) against platelet glycoprotein IIb/IIIa have been determined in baboons after bolus injections in doses (10 mg/kg) that block platelet receptor function for fibrinogen and other adhesive glycoproteins (absent platelet aggregation and bleeding times > 30 minutes without affecting circulating platelet counts). Results: Thrombus formation was eliminated by LJ-CP8 at sites of surgical endarterectomy in fresh segments of homologous aorta incorporated into chronic exteriorized arteriovenous femoral shunts (accumulation of indium 111-labeled platelets fell from 4.40 ± 0.89 × 109 platelets/cm in control animals [n = 6] to 0.23 ± 0.01 × 109 platelets/cm in treated animals [n = 4]; p < 0.005). The formation of thrombus was also abolished by LJ-CP8 at sites of 1 cm prosthetic vascular grafts (4 mm inner diameter polytetrafluoroethylene grafts) interposed into common carotid arteries (deposition of indium 111-labeled platelets decreased from 2.57 ± 0.43 × 109 platelets/cm [n = 5] to 0.16 ± 0.06 × 109 platelets/cm, [n = 4]; p = 0.004). However, LJ-CP8 injections produced substantial bleeding in the surgical wound during the first few hours after operation. Thirty days after operation all four graft implants were patent in LJ-CP8-treated animals compared with two of five in control animals (p = 0.06). Conclusions: We conclude that profound inhibition of platelet glycoprotein IIb/IIIa receptor function by single bolus injection of LJ-CP8 monoclonal antibody transiently abolishes platelet hemostatic function, eliminates acute thrombus formation at sites of endarterectomy and prosthetic vascular graft implants, and may improve vascular patency.

Original languageEnglish
Pages (from-to)294-304
Number of pages11
JournalJournal of Vascular Surgery
Volume17
Issue number2
DOIs
StatePublished - Feb 1993
Externally publishedYes

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