Platelet activation and erythrocyte lysis during brief exposure of blood to pathophysiological shear stress in vitro

BACKGROUND: Interaction of von Willebrand factor (VWF) with circulating platelets is the trigger for thrombosis in a region of arterial stenosis. These events are typically studied in vitro under conditions where platelets adhere to a VWF-coated surface. Our approach assesses platelet responses in the absence of adhesion. OBJECTIVE: To characterize extent of platelet activation and erythrocyte lysis in an artificial stenosis model. METHODS: Whole blood is perfused through a length of polyetheretherketone tubing that includes an artificial stenosis, comprising narrow-bore (89-381 μm) tubing. Secretion of [14C] serotonin and hemoglobin release was measured to evaluate platelet activation and hemolysis respectively at various perfusion rates and different stenosis dimensions. RESULTS: Platelet activation and erythrocyte lysis increased progressively with increasing perfusion rate and decreasing stenosis diameter; the length of the stenosis had negligible influence. Modest platelet activation (5-10% secretion of [14C] serotonin) occurred without significant erythrocyte lysis under a limited range of perfusion conditions (4-6 mL/min flow through a 127 μm stenosis). CONCLUSIONS: Our experimental approach mimics conditions in severe arterial stenosis or a mechanical heart valve. It could be a valuable aid in the development of novel drugs to treat arterial thrombosis and in the design of heart valves.