Repetitive Hypershear Activates and Sensitizes Platelets in a Dose-Dependent Manner

Implantation of mechanical circulatory support (MCS) devices-ventricular assist devices and the total artificial heart-has emerged as a vital therapy for advanced and end-stage heart failure. Unfortunately, MCS patients face the requirement of life-long antiplatelet and anticoagulant therapy to combat thrombotic complications resulting from the dynamic and supraphysiologic shear stress conditions associated with such devices, whose effect on platelet activation is poorly understood. We developed a syringe-capillary viscometer-the "platelet hammer"-that repeatedly exposed platelets to average shear stresses up to 1000 dyne/cm(2) for as short as 25 ms. Platelet activation state was measured using a modified prothrombinase assay, with morphological changes analyzed using scanning electron microscopy. We observed an increase in platelet activation state and post-high shear platelet activation rate, or sensitization, with an increase in stress accumulation (SA), the product of shear stress and exposure time. A significant increase in platelet activation state was observed beyond an SA of 1500 dyne-s/cm(2) , with a marked increase in pseudopod length visible beyond an SA of 1000 dyne-s/cm(2) . Utility of the platelet hammer extends to studies of other shear-dependent pathologies, and may assist development of approaches to enhance the safety and effectiveness of MCS devices and objective antithrombotic pharmacotherapy management.