Increased platelet glycoprotein IIb/IIIa activation precedes continuous-flow left ventricular assist device pump thrombosis events

Purpose Continuous-flow left ventricular assist devices (CFLVAD) in management of end-stage heart failure continues to expand. Adverse events however remain high. Better understanding of platelet activation in the context of CFLVAD therapy may help reduce bleeding and pump thrombosis (PT) risks to patients. Methods Whole blood was collected 15 days post CFLVAD implant. Blood samples were stimulated, stained with anti- CD61, gpIIb/IIIa complex (PAC-1), CD62P, fixed, and analyzed by flow cytometry. Unstimulated blood +/- RDGS were prepared as controls. Platelets were gated as CD61+ and CD62P and PAC-1 signal determined activation. Adverse events (PT/bleeding) were determined through INTERMACS. Results Median age was 62 years, 21% female, 17 implanted with centrifugal and 2axial flow pumps. Groups consisted of those without an adverse event (No event, n=11), PT (w or w/o bleed, n=3), and Bleeding event only (n=5). Healthy volunteers (n=5) were recruited to serve as controls. CFLVAD implantation alone did not increase PAC-1 platelet activation in patients 15 days post implant. In addition, CFLVAD implantation did not prevent platelets from becoming activated following stimulation. In patients with PT, PAC-1 was higher in unstimulated blood (9.9%) when compared to No event (2.22% p=0.023) and healthy controls (0.66% p=0.028). This elevation of PAC-1 was detected before the clinical manifestation of pump thrombosis (8, 139, 274 days). In addition, following stimulation, PAC-1 was increased significantly in PT patients (89.6%) compared to both No event (54.8% p Conclusion Platelet gpIIb/IIIa activation from PT patients was evident prior to thrombus development. PT patients even had the largest response to stimulation. This increase in platelet activation could serve as a predictor of device-related thrombosis events and may have important implications in targeted therapy to reduce PT in CFLVAD patients