LVAD-Associated Coagulopathy: Contribution of Phosphatidylserine (PS+) Cellular Microparticles to the Risk of Hemorrhage and Thrombosis in Patients with Non-Pulsatile Left Ventricular Assist Devices

Abstract

Purpose Left ventricular assist devices (LVADs) are associated with significant hemorrhagic and thrombotic complications, but the underlying mechanisms remain elusive. We examined whether cellular derived microparticles may be associated to adverse events in patients with LVADs. Methods and Materials We prospectively enrolled 15 patients undergoing elective implantation of a HeartMate II LVAD. Extensive coagulation profile including phosphatidylserine (PS+) cellular microparticles derived by platelets, leukocytes, erythrocytes, and endothelial cells was performed by flow cytometry. Samples were obtained upon admission (baseline), at discharge,at 3 months after discharge, and at the time of a clinically significant event. Patients were on an oral anticoagulation regimen of aspirin, warfarin (International Normalized Ratio, 2-3), and dipyridamole. Results Three patients had adverse events.At baseline, the mean percentage of PS+ microparticles in patients was higher than that in healthy controls (2.32%±1.65 vs. 0.98%±0.66) and gradually decreased during follow-up from 2.03%±1.35 (discharge) to 1.85%±1.22 (3 months). Patients with events had significantly more PS+ microparticles than did patients without events at 3 months (3.8%±0.75 vs. 1.85%±1.22, p Conclusions PS+ microparticles were elevated in patients before LVAD implantation, which is consistent with a hypercoagulable state. Anticoagulation after LVAD implantation appeared to reduce the amount of circulating PS+ microparticles in peripheral blood. Adverse thrombotic or bleeding events appeared to be preceded by elevated PS+ microparticles. The presence of these cell-derived particles may provide a procoagulant substrate that leads to significant adverse events.