Fibrinolytic agents inhibit platelet adhesion onto collagen type I- coated surfaces at high blood flow conditions

The effect of fibrinolytic agents on platelet adhesion onto insolubilized collagen type I was evaluated. Normal human whole blood samples were incubated with agents and perfused over collagen-coated surfaces in a parallel-plate flow chamber. Platelet adhesion and aggregation were analyzed by video microscopy and image processing. When blood was perfused at 1500/s, both streptokinase and urokinase, each at 500 U/ml, caused a significantly less normalized platelet deposition, compared with controls. At 480/s, platelet deposition was not different between controls and test samples. Inhibition of platelet deposition at high flow rates was partly due to inhibition of platelet adhesion. Both ristocetin- and ADP-induced platelet aggregation were inhibited in test samples. The agents caused proteolytic degradation of plasma fibrinogen, but no degradation of platelet glycoproteins Ib and IIb-IIIa (GPIb and GPIIb-IIIa) and of plasma von Willebrand factor in test samples prior to perfusion. Post-perfusion yon Willebrand factor degradation was not found. Plasmin may cause functional changes to plasma proteins and/or platelet receptors, altering their adhesive properties under flow. At high shear, fibrinogen degradation products may interfere with GPIIb-IIIa binding to insolubilized yon Willebrand factor, leading to decreased platelet adhesion. Inhibition of platelet adhesion by thrombolytic agents could help maintain vessel patency after recanalization in stenosed arteries.