Fibrinolysis Inhibits Shear Stress–Induced Platelet Aggregation

Background Shear stress–induced platelet aggregation may initiate arterial thrombosis at sites of pathological blood flow. Shear stress–induced platelet aggregation is mediated by von Willebrand factor (vWf) binding to platelet membrane glycoprotein (GP) Ib and GP IIb/IIIa. Tissue-type plasminogen activator (TPA) induces thrombolysis in coronary arteries through the local generation of plasmin. Plasmin also proteolyses GP Ib and plasma vWf. Methods and Results Because these effects could mitigate shear stress–induced platelet aggregation, we investigated the effect of fibrinolytic agents on platelet aggregation in response to a pathological shear stress of 120 dynes/cm2 generated by a cone-and-platen rotational viscometer. Plasmin inhibited shear stress–induced aggregation of washed platelets, and this was associated with a decrease in GP Ib. TPA, at concentrations ≥2000 IU/mL, significantly inhibited shear stress–induced platelet aggregation of platelet-rich plasma without a decrease in platelet GP Ib. I...