Role of erythrocytes in platelet activation during exposure to pathophysiological shear stress

Abstract

Interaction of von Willebrand factor (VWF) with circulating blood platelets is the initial trigger for thrombosis in an arterial stenosis. Exposure of blood to a high shear stress promotes such interaction. These events have previously been studied in vitro under conditions where the platelets adhere to a VWF‐coated surface. Our approach assesses platelet activation in the absence of adhesion. Whole blood is perfused through polyetheretherketone (PEEK) tubing that includes an artificial stenosis, comprising a short (4 cm) section of narrow‐bore (130 μm) tubing. The pressure differential across the stenosis was measured with a pressure transducer. Platelet activation was evaluated from secretion of [14C]serotonin, and erythrocyte lysis from release of hemoglobin. The pressure drop across the stenosis matched the predictions for laminar flow without turbulence. Platelet activation rose progressively with increasing perfusion rate (2–12 ml/min). We examined the role of erythrocytes in platelet activation by adjusting the hematocrit of the perfused blood. Platelet activation was minimal (mean increment of 1.9% in serotonin secretion at 12 ml/min flow) when the hematocrit was low (30%), but substantial (increment of 15.5%) with a high hematocrit (60%). In contrast, changes in the platelet count did not affect the extent of platelet activation. [Supported by the National Science Foundation.]