Synergistic action of severe wall injury and shear forces on thrombus formation in arterial stenosis: definition of a thrombotic shear rate threshold.

Objectives: This study attempted to determine the influence of progressive degrees of stenosis on platelet deposition onto a severely damaged vessel wall.

Background: The severity of wall injury and increased shear forces have been proposed as the determinants of thrombus formation and growth in arterial stenosis.

Methods: Carotid angioplasty was performed in 15 mongrel dogs to produce severe wall damage. Group I (n = 9) had arteries with damage only. In group II (n = 14), progressive degrees of stenosis were produced at the center of the dilated area. Acute thrombus formation was evaluated by angiography at the time of angioplasty and platelet deposition/cm2 quantified by indium-111 labeling 1 h after the procedure.

Results: Severe wall damage (group I) produced a significant increase in platelet deposition compared with control arterial segments (8.19 +/- 3.82 vs. 3.62 +/- 2.52 platelets x 10(6)/cm2 [mean +/- SD], p < 0.05), and the presence of a stenosis (group II) further increased platelet deposition (36.98 +/- 3.82 platelets x 10(6)/cm2, p < 0.05). Angiographic filling defects or total occlusion was found in seven of the arteries in group II but in none in group I (p < 0.05). A shear rate of approximately 5,000 s-1, corresponding to a critical stenosis of 70% and a 1.5- to 1.6-mm diameter, was found to identify the arteries in which thrombosis was likely to occur (p < 0.05). Four of 5 arteries < 1.5 to 1.6 mm in diameter had angiographic filling defects or occlusion compared with 1 of 13 with less severe stenosis (p < 0.01).

Conclusions: In low shear rate conditions, deep arterial injury will lead to mural thrombosis without further thrombus growth. When deep arterial injury occurs under critical local shear conditions, platelet deposition will be enhanced, and thrombosis may progress to total occlusion.