The Platelet Activity State Assay Can Detect Shear-Mediated Platelet Activation Associated With Thrombosis In LVAD Patients

Study: Shear-mediated platelet activation (SMPA) is a dominant mechanism driving thrombosis and thromboembolic (TH) complications in continuous-flow left ventricular assist devices (cf-LVADs). Here, we used the Platelet Activity State (PAS) assay to prospectively analyze in vivo the dynamics and progression of SMPA in 44 LVAD patients implanted with the HeartMateII (n=18) or the HeartWare HVAD (n=26). PAS values were correlated with clinical outcomes and TH adverse events. Methods: PAS was measured: i) 48 hours before LVAD implantation (PAS t0), to define patient-specific baseline values; ii) in the early post-implant (PAS t1); iii) during long-term follow-up after hospital discharge (PAS t2); when multiple PAS t2 values were available, the highest PAS was recorded. For patients who developed an event, PAS t2 was measured during the hospital stay that followed event occurrence. Results: Over 244 (iqr 58-760) days of median follow-up, PAS values did not significantly increase in the overall population (p=0.36). However, significant alterations of PAS (p<0.0001) were recorded in the sub-group of patients (n=6) who suffered an adverse event (pump thromboses: n=2; ischemic stroke: n=4). Notably, baseline PAS values (PAS t0) were associated with the development of TH complications during the long-term course of LVAD support (p=0.04), suggesting a potential risk prediction capability for PAS and patient-specifc platelet susceptibility to activation, which becomes overt with the contribution of the LVAD-induced shear stress. No differences were noted for clinical pre-operative variables, biochemical and coagulation parameters (LDH, INR), the type of pump or the anticoagulation/antiplatelet regimen. Our findings introduce the possibility of monitoring a clinical biomarker of SMPA associated with TH complications in patients with cf-LVADs and to guide further pharmacological improvements in the management of LVAD recipients.