The platelet hammer: In vitro platelet activation under repetitive hypershear.

Abstract

Mechanical circulatory support (MCS) devices, such as ventricular assist devices and the total artificial heart, have emerged as a vital therapy for advanced and end-stage heart failure. However, MCS patients face life-long antiplatelet and anticoagulant therapy to minimize thrombotic complications resulting from the dynamic and supraphysiologic device-associated shear stress conditions, whose effect on platelet activation is poorly understood. We repeatedly exposed platelets to average shear stresses up to 1000 dyne/cm(2) for as short as 25 ms in the "platelet hammer," a syringe-capillary viscometer. Platelet activation state was measured using a modified prothrombinase assay and morphological changes analyzed using scanning electron microscopy. An increase in stress accumulation (SA), the product of shear stress and exposure time, led to an increase in the platelet activation state and post-high shear platelet activation rate, or sensitization. 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). The platelet hammer may be used to study other shear-dependent pathologies and may ultimately enhance the safety and effectiveness of MCS devices and objective antithrombotic pharmacotherapy management.