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.
ASAIO J. 2018 Jul/Aug;64(4):462-471. doi: 10.1097/MAT.0000000000000680.
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.
非手术性出血（NSB）是心力衰竭（HF）患者接受左心室辅助装置（CF-LVAD）支持后的最常见临床并发症。本研究旨在探讨氧化应激与血小板糖蛋白 GPIbα 和 GPVI 脱落在 CF-LVAD 患者 NSB 发生率中的相关性。招募了 51 名接受 CF-LVAD 植入的 HF 患者和 11 名健康志愿者。在 1 个月的随访期间，14 名患者出现 NSB（出血组），而其他患者被认为是非出血组（n = 37）。所有患者在基线和每周间隔测量几种氧化应激生物标志物。测量血小板受体糖蛋白 GPIbα 和 GPVI 的表面表达和血浆成分。与健康志愿者相比，在两组 HF 患者的基线样本中发现氧化应激生物标志物和血小板 GPIbα 和 GPVI 受体脱落（表面表达降低和血浆水平升高）是预先存在的条件。与非出血组相比，出血组患者在植入后暂时观察到氧化应激生物标志物和血小板糖蛋白受体脱落显著升高。观察到氧化应激生物标志物与血小板糖蛋白受体脱落之间存在强烈的显著相关性，表明氧化应激可能在导致 CF-LVAD 患者 NSB 的血小板整合素脱落中起作用。GPIbα 和 GPVI 的受试者工作特征分析表明，NSB 的可能性对 CF-LVAD 患者的出血并发症具有预测能力。总之，氧化应激升高可能在 NSB 事件中发挥作用 GPIbα 和 GPVI 脱落。因此，氧化应激和 GPIbα 和 GPVI 脱落可能被用作这些患者出血风险分层的潜在生物标志物。
