Oxidative stress induced modulation of platelet integrin α2bβ3 expression and shedding may predict the risk of major bleeding in heart failure patients supported by continuous flow left ventricular assist devices

•Oxidative stress and integrin α2bβ3 shedding were observed in CF-LVAD patients.•Oxidative stress is positively associated with integrin α2bβ3 shedding.•Integrin α2bβ3 shedding has a predictive power of major bleeding complications.•Integrin α2bβ3 shedding may be responsible for major bleeding in CF-LVAD patients.

IntroductionOxidative stress and platelet integrin α2bβ3 plays important role in the process of hemostasis and thrombosis. We hypothesized that device-induced patient specific oxidative stress and integrin α2bβ3 shedding may be linked to major bleeding complication (MBC) in heart failure (HF) patients supported by continuous flow left ventricular assist devices (CF-LVADs).Materials and methodsWe recruited 47patients implanted with CF-LVADs and 15 healthy volunteers. Fourteen patients developed MBC (bleeder group) within one month after implantation while others were considered non-bleeder group (n = 33). Oxidative stresses were evaluated by measuring reactive oxygen species (ROS) in platelets, superoxide dismutase (SOD) activity, total antioxidant capacity (TAC) and oxidized low density lipoprotein (oxLDL). Assessments of α2bβ3 were carried out using flow cytometry and ELISA.ResultsBiomarkers of oxidative stress and α2bβ3 shedding (decreased surface expression and higher plasma levels) were found to be preexisting condition in all HF patients prior to CF-LVAD implantation compared to the healthy volunteers. Significantly elevated levels of ROS and oxLDL; concomitant depletion of SOD and TAC; and α2bβ3 shedding were observed in the bleeder group temporarily in comparison to the non-bleeder group after CF-LVAD implantation. A significantly strong association between α2bβ3 shedding and biomarkers of oxidative stress was observed; suggesting a potential role of oxidative stress in platelet integrin shedding leading to MBC after CF-LVAD implantation. Moreover, a receiver operating characteristic (ROC) analysis indicated that the likelihood of MBC data from Integrin α2bβ3 shedding had a predictive power of MBC in CF-LVAD patients.ConclusionsOxidative stress might play a potential role in accelerating α2bβ3 shedding and platelet dysfunction, resulting in MBC in CF-LVAD patients. Integrin α2bβ3 shedding may be used to refine bleeding risk stratification in CF-LVAD patients.