Shear-Mediated Platelet Activation Enhances Thrombotic Complications in Patients With LVADs 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%). PAS 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.

Platelet activation is a preoperative risk factor for the development of thromboembolic complications in patients with continuous-flow left ventricular assist device.

AIMS: To correlate the dynamics of platelet activation with the development of thromboembolic events in patients with continuous-flow left ventricular assist device (cf-LVAD). METHODS AND RESULTS: The platelet activity state (PAS) assay was utilized to evaluate platelet activation in 68 cf-LVAD patients implanted with the HeartMate II (n = 15, 22%), HeartMate 3 (n = 15, 22%), or HeartWare HVAD (n = 38, 56%). PAS was measured preoperatively, early post-implant, and at long-term follow-up (1, 3, 6, 12, 18, and 24 months post-implant). PAS was also measured at the occurrence of adverse events in patients who developed thrombotic complications. Data on patient demographics, medical history, antithrombotic therapy, and coagulation parameters were also analysed. Over a median follow-up of 602 (234-942) days, PAS values did not increase over time in the overall population (P = 0.15). However, PAS measured at event was 15-fold higher in the six patients (9%) who suffered pump thrombosis (n = 2) or ischaemic stroke (n = 4) vs. the rest of the population [6.67% (5.59%-11.98%) vs. 0.45% (0.33%-0.75%); P = 0.012], despite comparable coagulation profile. Pre-implant PAS values were 4.5-fold higher in these patients [1.90% (1.24%-3.17%) vs. 0.42% (0.32%-0.72%); P = 0.006]. Neither preoperative variables nor the type of the pump or the antiplatelet strategy were associated with a higher risk of complications. CONCLUSIONS: Thrombotic events are associated with altered PAS values. Moreover, baseline elevated PAS values in patients who developed thrombotic events suggest patient-specific tendency to post-implant thromboembolic complications. Prospectively, systematic monitoring of PAS might guide the development of refined patient-tailored antithrombotic strategies and the technological improvement of LVAD design.