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

Abstract

Non-surgical bleeding (NSB) is one of the major clinical complications for expanding usage of left ventricular assist devices (LVAD) in patients with end-stage heart failure. It has been reported that non-physiological shear stress caused by LVADs could induce platelet receptor shedding which leads to bleeding disorders caused by dysfunctions in the coagulation system. Therefore, we focused on the characterization of platelets to compare patients with bleeding complications and patients without coagulation disorder after LVAD implantation. Blood samples were obtained from LVAD patients with postoperative NSB (bleeder group, n=20) and compared to LVAD patients without NSB (non-bleeder group, n=20). Platelet receptors (platelet endothelial cell adhesion molecule-1, protease-activated receptor-1, GPIbα), platelet activation (P-selectin, CD63 and GPIIb/IIIa) and platelet reactive oxygen species (ROS) production was quantified by flow cytometry. Aggregation capacity induced by adenosine diphosphate (ADP) and thrombin receptor-activating peptide (TRAP) was evaluated by aggregometry. The surface expression level of GPIIb/IIIa, P-selectin and GPIbα on platelets was decreased in bleeders (GPIIb/IIIa: 32662 ± 1316 U; P-selectin: 475 ± 69 U; GPIbα: 393 ± 44 U) compared to non-bleeders (GPIIb/IIIa: 37247 ± 1599 U, p = 0.03; P-selectin: 845 ± 116 U, p = 0.09; GPIbα: 538 ± 53 U, p=0.04). Additionally, the mean fluorescence intensity of both ADP-activated P-selectin and CD31 expressing platelets was reduced in bleeders (P-selectin: 970 ± 81 U; CD31: 6889 ± 371 U) compared to non-bleeders (P-selectin: 1311 ± 130 U, p = 0.03; CD31: 8558 ± 664 U, p = 0.03). Bleeders showed a higher content of ROS formation in platelets (88.7 ± 2.5%) than non-bleeders (81.5 ± 2.1%, p = 0.03). The findings of this study suggested that changes in platelet receptor pattern of three different platelet receptors (GPIIb/IIIa, P-selectin and GPIbα) and elevated oxidative stress levels may play a role in patients with bleeding complications following LVAD implantation. These results might help to understand the altered hemostatic function as an important cause for NSB in patients on LVAD support.