Time course of the effects of a single bolus injection of F(ab')2 fragments of the antiplatelet GPIIb/IIIa antibody 7E3 on arterial eversion graft occlusion, platelet aggregation, and bleeding time in dogs.

Abstract

The time course of the effects of a single intravenous bolus injection of 10 mg/kg aspirin or 0.8 mg/kg F(ab') 2

Contribution of platelets and the vessel wall to the antithrombotic effects of a single bolus injection of Fab fragments of the antiplatelet GPIIb/IIIa antibody 7E3 in a canine arterial eversion graft preparation.

“…Whatever the mechanism, the dissociation of the hemostatic from the thrombogenic properties of platelets could be valuable from a therapeutic standpoint. The results of the present study, taken together with those of the accompanying study, 7 which defines the time course of the antithrombotic effect, indicate that concomitant heparin anticoagulation potentiates the antithrombotic effect of 7E3-Fab fragments but that heparin anticoagulation alone can prevent neither early nor delayed eversion graft occlusion. Indeed, in the control group of the present study, which received intense continuous anticoagulation but no antibody, graft occlusion was consistently observed; in the antibody group of the accompanying study, which received subcutaneous heparin without aPTT prolongation at 24 hours, extensive occlusive or subocclusive thrombus was observed.…”

“…The model was used essentially as described elsewhere 7 " but with the following modifications. A central venous catheter was placed and tunneled to the upper part of the back for connection to a portable elastomeric infusion pump (Homepump, Block Medical Inc).…”

“…The results of the microscopic evaluation of carotid/ femoral eversion grafts with extent and composition of the thrombus graded as defined elsewhere 7 are summarized in Table 5. The extent of arterial thrombosis was significantly different between the control group and the graft donor group (P= .002 by Kruskal-Wallis analysis) and between the control group and the platelet recipient groups (P=.OO9 by Kruskal-Wallis analysis).…”

“…3 The temporal dependence of the thrombogenicity of the damaged vessel wall has been demonstrated in several studies, 46 but the mechanisms of "passivation" remain largely unknown. We have observed 7 that a single bolus injection of 0.8 mg/kg F(ab') 2 fragments of the monoclonal antiplatelet glycoprotein (GP) Ilb/IIIa receptor antibody 7E3, 7E3-F(ab% 8 abolished early platelet-mediated occlusion of arterial eversion grafts in a canine preparation. Persistent graft patency was observed in approximately 50% of the animals for up to 72 hours after study drug injection, a time at which both the template bleeding times and platelet dogs (P=.O34 versus control), whereas all of the 5 eversion segments were patent at 24 hours (P<.005 versus control).…”

“…7 However, persistent graft patency was associated with moderate to extensive mural thrombosis. Similar results were also obtained in an electrolytic injury model in dogs in which 7E3 produced sustained coronary artery patency over a 6-day period.…”