Rapid Platelet Accumulation Leading to Thrombotic Occlusion

Abstract

Platelet thrombosis under arterial conditions remains a large clinical problem. Previous in vitro experiments have concentrated on early adherence without thrombotic occlusion. We have developed a controllable hemodynamic system that creates intravascular thrombosis to occlusion. Lightly heparinized (3.5 USP units/mL), whole, porcine blood is perfused through a 1.5 mm inner diameter, tubular, collagen-coated stenosis. The microscopic growth of thrombus is optically recorded using a high resolution CCD camera. Occlusive thrombus is examined using microcomputed tomography and histology. Thrombus consistently formed in the throat of the stenosis where wall shear rates were greatest. Rapid platelet accumulation (RPA) reached rates as high as 13.7 μm³ μm⁻² min⁻¹. Total occlusion of flow occurred after 17 ± 2.6 min (n = 6). The average thrombus volume accumulation of 7.8 ± 3.5 μm³ μm² min⁻¹ occurred under very high wall shear rates exceeding 100,000 s⁻¹. Significant volumes of thrombus did not form until 7.6 ± 3.6 min after the onset of flow, a delay consistent with activation of adherent mural platelets. Platelets did not accumulate with large volume for normal wall shear rates −1. Very high wall shear rates stimulate the capture of millions of circulating platelets with exposure times <2 ms in an arterial stenosis.