Device-Induced Platelet Dysfunction in Patients after Left Ventricular Assist Device Implantation

Abstract

<h3>Purpose</h3> Non-surgical bleeding (NSB) is a major clinical complications for expanding usage of left ventricular assist devices (LVAD). It has been reported that non-physiological shear stress caused by LVADs could altered platelet receptor expression which leads to bleeding disorders. Because bleeding diathesis could be multifactorial, we focused on the combined characterization of platelet receptor expression patterns and oxidative stress to compare patients with and without bleeding complications after LVAD implantation in a monocentric, prospective study. <h3>Methods</h3> Blood samples were obtained from LVAD patients with postoperative NSB (bleeder group, n=19) and compared to LVAD patients without NSB (non-bleeder group, n=20). The platelet receptors platelet endothelial cell adhesion molecule-1 (PECAM-1), protease-activated receptor-1 (PAR-1), GPIbα, P-selectin, CD63 and GPIIb/IIIa as well as the production of intraplatelet ROS were quantified by flow cytometry. Aggregation capacity was evaluated by aggregometry. <h3>Results</h3> The surface expression level of P-selectin and GPIbα on platelets was decreased in bleeders (P-selectin: 465±72U; GPIbα: 435±41U) compared to non-bleeders (P-selectin: 859±115U, p<0.01; GPIbα: 570±49U, p=0.04). Additionally, the mean fluorescence intensity of ADP-activated P-selectin and PECAM-1 expressing platelets were reduced in bleeders (P-selectin: 944±84U; PECAM-1: 6,722±419U) compared to non-bleeders (P-selectin: 1,269±130U, p=0.04; PECAM-1: 8,542±665U, p=0.03). Bleeders showed a higher amount of ROS formation in platelets (88.0±2.6%) than non-bleeders (81.5±2.1%, p=0.05). <h3>Conclusion</h3> Our findings suggested that changes of three platelet receptors (GPIbα, P-selectin and PECAM-1) and elevated oxidative stress may play a role in patients with bleeding complications following LVAD implantation. These results might help to explain the high incidence of spontaneous hemorrhage during LVAD support through an altered platelet function.