Effects of Elapsed Time on Downstream Platelet Adhesion Following Exposure to Transiently Elevated Upstream Shear Forces

Abstract

Transient exposure to elevated shear forces pre-activates platelets for enhanced downstream adhesion, but how far downstream these priming effects persist is not known. We found that platelet adhesion to downstream capture region containing one of the three immobilized platelet binding proteins: fibrinogen, collagen, or von Willebrand factor, changed after platelets flowed through an upstream stenotic region. These platelet capture regions were placed at three different distances from the upstream stenotic region. Platelet adhesion increased with the increase of upstream wall shear rates from 1620 s-1 to 11560 s-1 for all three proteins, but only the adhesion to fibrinogen increased significantly with the distance between the upstream stenotic region and downstream capture region. Platelet adhesion to collagen remained essentially independent on the distance and adhesion to von Willebrand factor marginally increased with the distance after transient platelet exposure to higher upstream shear rates. The results implied that the activation of fibrinogen receptor GPIIb/IIIa by transient exposure to high upstream wall shear rates progresses in a time-dependent manner during the flow of platelets to the downstream capture regions. The highly elevated upstream wall shear rate of 11560 s-1 altered the morphology of many platelets adhered to downstream fibrinogen from their native ellipsoidal to spread circular form. The platelet shape analysis showed that longest periods of post-stenotic flow increased the surface coverage fraction of ellipsoidal platelet population and decreased the surface coverage fraction of fully spread platelets on fibrinogen after both elevated upstream wall shear rates.