Impaired Platelet Activation in Patients after Left Ventricular Assist Device Implantation

Objectives: One of the most common clinical complications in patients with an implanted left ventricular assist device (LVAD) is recurrent nonsurgical bleeding (NSB). Nonphysiological shear stress caused by LVADs may contribute to platelet receptor shedding and thereby facilitate platelet dysfunction which is an important cause of major bleeding during LVAD support. We investigated the device-induced alterations of platelets to identify patients at risk of bleeding after LVAD implantation.

Methods: Blood samples were collected from LVAD patients with postoperative NSB (bleeder group, n = 15) and compared to LVAD patients without NSB (non-bleeder control group, n = 15). Percentages and mean fluorescence intensities (MFIs) of the surface expression of platelet receptors (platelet endothelial cell adhesion molecule-1, protease-activated receptor-1, GPIbα, GBIIb/IIIa), platelet activation (P-selectin, CD63, and GPIIb/IIIa), and platelet reactive oxygen species (ROS) production were quantified by flow cytometry. Aggregation capacity induced by adenosine diphosphate (ADP) and thrombin receptor-activating peptide (TRAP) was evaluated by aggregometry.

Results: The surface expression level of GPIIb/IIIa and P-selectin in platelets was decreased in bleeders (GPIIb/IIIa: 30,008 ± 2,189 U; P-selectin: 550 ± 102 U) compared to non-bleeders (GPIIb/IIIa: 36,606 ± 2,056 U, p = 0.04; P-selectin: 1,017 ± 161 U, p = 0.02). Additionally, the percentage of ADP-activated GPIbα+ platelets was reduced in bleeders (89.8 ± 4.6%) compared to non-bleeders (93.9 ± 4.7%, p = 0.02). Bleeders showed a higher content of ROS formation in platelets (90.0 ± 3.1%) and a lower aggregation capacity of TRAP-induced platelets (80.9 ± 4.2%) than non-bleeders (ROS: 82.3 ± 2.5%, p = 0.04; TRAP-induced aggregation: 90.6 ± 2.0%, p = 0.05).

Conclusion: An impaired platelet receptor activation for three different platelet receptors (GPIIb/IIIa, P-selectin, and GPIbα) and an increased oxidative stress level were detected in patients with bleeding complications following LVAD implantation. These findings might provide a new perspective to understand bleeding complications in LVAD-supported patients and could be helpful to identify patients at risk for NSB.