title: Intraplatelet reactive oxygen species, mitochondrial damage and platelet apoptosis augment non-surgical bleeding in heart failure patients supported by continuous-flow left ventricular assist device.
abstract: Non-surgical bleeding (NSB) is the most common clinical complication among heart failure (HF) patients supported by continuous-flow left ventricular assist devices (CF-LVADs). Understanding the role of platelet functionality contributing to NSB after CF-LVAD implantation is crucial for prevention and management of this adverse event. The aim of this study was to examine the role of intraplatelet reactive oxygen species (ROS) and platelet damage on the incidence of bleeding events after CF-LVAD implantation in HF patients. We recruited 25 HF patients implanted with CF-LVADs and 11 healthy volunteers as the control. Intraplatelet ROS generation, platelet mitochondrial damage and platelet apoptosis were quantified by flow cytometry. Among 25 patients, 8 patients developed non-surgical bleeding within one month after CF-LVAD implantation. Intraplatelet ROS, depolarized and apoptotic platelet were found to be pre-existing conditions in all baseline samples of the 25 HF patients when compared to the healthy volunteers. There was no significant difference in the levels of ROS between the non-bleeder and the bleeder groups prior to CF-LVAD implantation, although we noticed 2-fold and 1.5-fold rise in depolarized and apoptotic platelets, respectively, in the bleeder group compared to those in the non-bleeder group. Post implant levels of intraplatelet ROS, depolarized and apoptotic platelets increased and remained elevated in the bleeder group, whereas periodic decreases were noticed in the non-bleeder group, suggesting the potential role of platelet damage on bleeding incidence. ROS generation after CF-LVAD implantation positively associated with platelet apoptosis (ρ = 0.4263, p = 0.0023) and depolarized platelets (ρ = 0.4774, p = 0.0002), especially the latter. In conclusion, elevated intraplatelet ROS and platelet damage may be linked to the NSB among HF patients supported by CF-LVAD. These results provide mechanistic insights into the bleeding complication in patients with CF-LVAD support.
authors.affiliation: Department of Surgery, Artificial Organs Laboratory, University of Maryland School of Medicine , Baltimore, Maryland , USA .
authors.forename: Nandan K
authors.initials: NK
authors.lastname: Mondal
authors.forename: Erik N
authors.initials: EN
authors.lastname: Sorensen
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Hiivala
authors.forename: Erika D
authors.initials: ED
authors.lastname: Feller
authors.forename: Si M
authors.initials: SM
authors.lastname: Pham
authors.forename: Bartley P
authors.initials: BP
authors.lastname: Griffith
authors.forename: Zhongjun J
authors.initials: ZJ
authors.lastname: Wu
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis; D001777:Blood Coagulation; D001792:Blood Platelets / Q000378:metabolism*; D016022:Case-Control Studies; D005260:Female; D006333:Heart Failure / Q000150:complications* / Q000175:diagnosis / Q000209:etiology / Q000378:metabolism* / Q000628:therapy; D006353:Heart-Assist Devices; D006470:Hemorrhage / Q000209:etiology*; D006801:Humans; D008297:Male; D053078:Membrane Potential, Mitochondrial; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism*; D010979:Platelet Function Tests; D017382:Reactive Oxygen Species / Q000378:metabolism*; D055815:Young Adult
chemical_list: D017382:Reactive Oxygen Species
keywords: Heart failure; intraplatelet reactive oxygen species; left ventricular assist device; mitochondrial damage; non-surgical bleeding; platelet apoptosis