Shear-Mediated Platelet Activation Enhances Thrombotic Complications in Patients With LVAD and Is Reversed After Heart Transplantation

We present a time-series analysis of shear-mediated platelet activation (SMPA) in a patient supported by a left ventricular assist device (LVAD) who developed recurrent thromboembolic events over the course of support. The patient showed marked alterations of SMPA as quantified via the platelet activity state (PAS) assay. At the time of a first pump thrombosis, PAS was equal to 16.2 ± 2.1%, indicating a significant level of SMPA. A moderate decrease of PAS was observed 30 days after pump exchange (PAS = 9.5 ± 1.0%). A sudden PAS increase was recorded after 60 days (PAS = 60.5 ± 4.3%), and an ischemic stroke with hemorrhagic transformation was subsequently diagnosed at 120 days after pump exchange (PAS = 86.9 ± 7.5%); high PAS values did not recover over time likely because of sustained platelet activation from the inflammatory milieu caused by a driveline infection occurred at 240 days of support (PAS = 84.4 ± 7.3%). Platelet activity state values were completely reversed after heart transplantation (PAS = 0.6 ± 0.1%), demonstrating resolution of SMPA. This study provides further insight into our understanding of the pathogenesis of LVAD thrombosis, addressing SMPA as a relevant key factor associated with thrombotic complications. With the PAS assay, we have identified a reliable biomarker to promote tailored pharmacological therapy for the prevention of thromboembolic events in patients with LVADs.