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Association of Oxidative Stress and Platelet Receptor Glycoprotein GPIbα and GPVI Shedding During Nonsurgical Bleeding in Heart Failure Patients With Continuous-Flow Left Ventricular Assist Device Support

Mondal, Nandan K.*†; Chen, Zengsheng*†; Trivedi, Jaimin R.*; Sorensen, Erik N.; Pham, Si M.; Slaughter, Mark S.*; Griffith, Bartley P.; Wu, Zhongjun J.*†

doi: 10.1097/MAT.0000000000000680
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Nonsurgical bleeding (NSB) in heart failure (HF) patients with continuous-flow left ventricular assist device (CF-LVAD) support is the most common clinical complication. The aim of this study was to investigate the association between oxidative stress and platelet glycoproteins GPIbα and GPVI shedding on the incidence of NSB in CF-LVAD patients. Fifty-one HF patients undergoing CF-LVAD implantation and 11 healthy volunteers were recruited. Fourteen patients developed NSB (bleeder group) during 1 month follow-up duration, while others were considered nonbleeder group (n = 37). Several biomarkers of oxidative stress were quantified at baseline and weekly intervals in all patients. Surface expression and plasma elements of platelet receptor glycoproteins GPIbα and GPVI were measured. Oxidative stress biomarkers and platelet GPIbα and GPVI receptor-shedding (decreased surface expression and higher plasma levels) were found to be preexisting conditions in baseline samples of both groups of HF patients when compared with healthy volunteers. Significantly elevated oxidative stress biomarkers and platelet glycoprotein receptor shedding were observed in postimplant bleeder group temporarily when compared with nonbleeder group. Strong significant associations between biomarkers of oxidative stress and platelet glycoprotein receptor shedding were observed, suggesting a possible role of oxidative stress in platelet integrin shedding leading to NSB in CF-LVAD patients. Receiver operating characteristic analyses of GPIbα and GPVI indicated that the likelihood of NSB had a predictive power of bleeding complication in CF-LVAD patients. In conclusion, elevated oxidative stress may play a role in GPIbα and GPVI shedding in the event of NSB. Thus, oxidative stress and GPIbα and GPVI shedding may be used as potential biomarkers for bleeding risk stratification in those patients.

From the *Department of Cardiovascular and Thoracic Surgery, Cardiovascular Innovation Institute, University of Louisville School of Medicine, Louisville, Kentucky; Department of Surgery, Artificial Organs Laboratory, University of Maryland School of Medicine, Baltimore, Maryland; and Department of Clinical Engineering, University of Maryland Medical Center, Baltimore, Maryland.

Submitted for consideration May 2017; accepted for publication in revised form July 2017.

Disclosure: The authors have no conflicts of interest to report.

The described research was sponsored by the National Institutes of Health (Grant 1R01HL124170-01A1).

Correspondence: Zhongjun J. Wu, Department of Surgery, University of Maryland School of Medicine, 10 South Pine Street, MSTF 434A, MD 21201. Email: zwu@som.umaryland.edu.

Copyright © 2018 by the American Society for Artificial Internal Organs