Left ventricular assist devices promote changes in the expression levels of platelet microRNAs.

Introduction: MicroRNAs (miRs) emerged as promising diagnostic and therapeutic biomarkers in cardiovascular diseases. The potential clinical utility of platelet miRs in the setting of left ventricular assist device (LVAD) support is unexplored. Methods: We prospectively measured the expression levels of 12 platelet miRs involved in platelet activation, coagulation, and cardiovascular diseases in LVAD patients by quantitative real-time polymerase chain reaction. Data were longitudinally measured before LVAD implant and after 1, 6, and 12 months of LVAD support, and compared with those measured in healthy volunteers (controls). In silico analysis was also performed to identify pathways targeted by differentially expressed miRs. Results: Data from 15 consecutive patients and 5 controls were analyzed. Pre-implant expression levels of platelet miR-126, miR-374b, miR-223, and miR-320a were significantly different in patients vs. controls. The expression levels of platelet miR-25, miR-144, miR-320, and miR-451a changed significantly over the course of LVAD support; in silico analysis revealed that these miRs are implicated in both cardiac- and coagulation-associated pathways. Furthermore, the patients who suffered from bleeding (n = 5, 33%) had significantly higher pre-implant expression levels of platelet miR-151a and miR-454 with respect to the patients who did not. The same miRs were also differentially expressed in bleeders following LVAD implantation early before the clinical manifestation of the events. Discussion: This study provides a proof-of-concept evidence of significant modulation of platelet miRs expression driven by LVADs. The possible existence of a platelet miRs signature predictive of the development of bleeding events warrants further validation studies.

Platelet activation state in early stages of COVID-19.

BACKGROUND: Platelet activation at the early stage of COVID-19 is poorly described. The need for antiplatelet therapy in patients with COVID-19 remains controversial. We characterized the platelet activation profile in hospitalized patients at the early stage of COVID-19 using the modified prothrombinase Platelet Activation State (PAS) Assay. METHODS: Sixteen patients admitted to the emergency department of the IRCCS San Raffaele Hospital (Milan, Italy) between February 8 and April 2021 were enrolled. All patients presented with respiratory symptoms and tested positive for severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2). Platelet activation was measured via the PAS Assay within 24 hours from patients' hospital admission. Data were compared with those measured in N.=24 healthy subjects (controls). RESULTS: Platelet activation was significantly higher in COVID-19 patients with respect to controls (PAS=0.63 [0.58-0.98%] vs. 0.46 [0.40-0.65%], respectively; P=0.03). Of note, highest PAS values were measured in the two patients with the worst clinical outcome, i.e., death because of respiratory failure (PAS=2.09% and 1.20%, respectively). No differences in standard coagulation parameters were noted between these two patients and those who were later discharged home. CONCLUSIONS: This study provides evidence of significant platelet activation state at the early stage of COVID-19 and suggests that the patient-specific platelet activation profile is a reliable clinical marker to stratify COVID-19 patients at high risk of poor clinical outcome who might potentially benefit from antiplatelet therapy.

Bleeding in patients with continuous-flow left ventricular assist devices: acquired von Willebrand disease or antithrombotics?

OBJECTIVES: To evaluate the competing pro-haemorrhagic contribution of acquired von Willebrand (vW) disease and antithrombotic therapy in patients implanted with continuous-flow left ventricular assist devices (LVADs). METHODS: We compared the extent of vW factor (vWf) degradation [vWf antigen (vWf:Ag)] and a decrease of functional activity of large vWf multimers [vWf collagen binding (vWf:CB)] in LVAD patients who did and did not suffer from bleeding. Data were measured pre-implant, at short-term (t1: <3 months) and long-term (t2: >12 months) follow-up. The occurrence of primary bleeding events, as well as bleeding recurrence, was correlated with patient-specific vWf profile and antithrombotic regimen. Indeed, patients were discharged on warfarin (international normalized ratio: 2-2.5) and aspirin, with the latter withhold after a first bleeding episode. RESULTS: Fifty-three patients were enrolled. The median follow-up was 324 (226-468) days. We recorded 25 primary bleeding events (47% of patients). All primary events occurred in patients on warfarin and aspirin. Both vWf:Ag and vWf:CB decreased significantly post-implant (P = 0.0003 and P < 0.0001), and patients showing pathological vWf:CB/vWf:Ag ratio (<0.7) increased progressively over the time of support (pre-implant = 26%, t1 = 58%, t2 = 74%; P < 0.0001). Of note, activity of large vWf multimers of bleeders was significantly lower at t2 with respect to non-bleeders (vWf:CB: 61 (36-115) vs 100 (68-121), P = 0.04; vWf:CB/vWf:Ag ratio: 0.36 (0.26-0.61) vs 0.58 (0.33-0.96), P = 0.04). Despite these marked differences in the vWf profile, following aspirin discontinuation only 3 patients had bleeding recurrence. CONCLUSIONS: Aspirin contributes significantly to haemorrhagic events in the background of acquired vW disease; its discontinuation significantly reduces bleeding recurrence. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT03255928; ClinicalTrials.gov Identifier: NCT03255928.