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

Abstract

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. To characterize extent of platelet activation and erythrocyte lysis in an artificial stenosis model. 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. 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). 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.