Examination of the roles of glycoprotein Ib and glycoprotein IIb/IIIa in platelet deposition on an artificial surface using clinical antiplatelet agents and monoclonal antibody blockade

Abstract

The mechanism of platelet thrombus growth on an artificial surface is incompletely understood. While glycoprotein (GP)Ib and GPIIb/IIIa are required for normal attachment and thrombus formation on subendothelium, their roles in platelet deposition to artificial surfaces remain unclear. Using selected platelet inhibitors (aspirin [ASA], low molecular weight dextran, monoclonal antibodies 10E5 [v GPIIb/IIIa], and 6D1 [GPIb]) we examined the mechanism of platelet deposition to polyethylene (PE) surfaces under steady laminar and oscillatory flow conditions. Polyethylene-100 (PE-100) tubes (0.86 mm internal diameter) were perfused under steady laminar flow with citrated human whole blood reconstituted with 111indium-labeled platelets at 312 seconds-1 shear rate in the presence and absence of platelet inhibitors. The effect of oscillatory flow on platelet deposition was examined in a microwell system using 3/16-inch diameter discs of National Heart, Lung, and Blood Institute primary reference PE as the test surface. ASA and dextran did not significantly (P > .05) inhibit platelet deposition in laminar flow (not tested in oscillatory). Antibody 10E5 was a potent inhibitor (laminar <1%, P < .0001, oscillatory <1.6%, P < .01) of platelet deposition in both systems, and in this case, true adhesion (first attached layer) was blocked. Antibody 6D1 unexpectedly inhibited 70% of platelet deposition (P < .01) in steady laminar flow and 56.5% in oscillatory flow (P