NETs联合中性粒细胞指标对ECMO辅助下血栓并发症的预警价值

Predictive Value of NETs combined with Neutrophil Indicators for Thromboembolic Complications in Patients under ECMO Assistance

摘要

目的 探讨中性粒细胞胞外诱捕网（neutrophil extracellular traps，NETs）相关指标联合中性粒细胞功能指标对体外膜肺氧合（extracorporeal membrane oxygenation，ECMO）辅助患者血栓并发症的预警价值。方法 本研究为单中心前瞻性队列研究，连续纳入2023年1月至2024年12月在内蒙古自治区人民医院接受ECMO辅助治疗的患者100例。根据有无血栓并发症分为非血栓并发症组和血栓并发症组。根据主要不良心血管事件（major adverse cardiovascular events，MACE）发生的人数，将总研究人数分为MACE组和非MACE组。收集患者一般资料、病史及ECMO相关参数。检测血常规、凝血功能、NETs标志物[髓过氧化物酶-DNA复合物（myeloperoxidase-DNA complexes，MPO-DNA）、瓜氨酸化组蛋白H3（citrullinated histone H3，CitH3）]及中性粒细胞功能指标：表面标志物〔分化簇11b（cluster of differentiation 11b，CD11b）、L-选择素（L-selectin，CD62L）〕及活性氧（reactive oxygen species，ROS）生成。通过影像学检查及临床评估判定血栓并发症发生情况。采用t检验、卡方检验、相关性分析及受试者工作特征（receiver operating characteristic，ROC）曲线分析评价各指标的预测价值。结果 100例患者中，30例（30.0%）发生血栓并发症。与非血栓组相比，血栓组MPO水平显著升高（P < 0.05）。随访期间共23例发生MACE，MACE组MPO及血清铜蓝蛋白（ceruloplasmin，CER）水平均显著高于非MACE组（P < 0.05）。CER与MPO水平具有相关性（r = 0.333，P < 0.001）。ROC分析显示，MPO预测MACE的效能高于CER（AUC：0.867 vs 0.856，P < 0.05），而CER预测血栓并发症的效能高于MPO（AUC：0.865 vs 0.825，P < 0.05）。结论 NETs相关指标联合中性粒细胞功能指标在ECMO辅助患者血栓并发症的预测中具有较好的预警价值，可为临床风险评估提供依据。

Abstract

Objective To evaluate the predictive value of neutrophil extracellular traps (NETs)–related indicators combined with neutrophil functional indices for thrombotic complications in patients receiving extracorporeal membrane oxygenation (ECMO) support. Methods The single-center prospective cohort study consecutively enrolled 100 patients receiving ECMO-assisted therapy at the Inner Mongolia Autonomous Region People's Hospital from January 2023 to December 2024. Patients were classified into the non-thrombotic complication group and the thrombotic complication group based on the presence or absence of thrombotic complications. The total study population was further divided into the MACE group and the non-MACE group according to the incidence of MACE events. Laboratory assessments included routine blood tests, coagulation function, NETs markers [myeloperoxidase-DNA complexes (MPO-DNA) and citrullinated histone H3 (CitH3)], and neutrophil functional indices [surface markers (CD11b, CD62L) and reactive oxygen species (ROS) production] were measured. Thrombotic complications were identified through imaging examinations and clinical evaluation. The predictive value of each indicator was assessed using t-test, chi-square test, correlation analysis, and receiver operating characteristic (ROC) curve analysis. Results Among the 100 patients, 30 (30.0%) developed thrombotic complications. MPO levels were significantly higher in the thrombosis group than in the non-thrombosis group (P < 0.05). During follow-up, 23 patients experienced MACE. Levels of MPO and ceruloplasmin (CER) were significantly higher in the MACE group (P < 0.05). CER levels were correlated with MPO levels (r = 0.333, P < 0.001). ROC analysis showed that MPO had better predictive performance for MACE than CER (AUC: 0.867 vs 0.856, P < 0.05), whereas CER demonstrated better performance in predicting thrombotic complications than MPO (AUC: 0.865 vs 0.825, P < 0.05). Conclusion NETs-related indicators combined with neutrophil functional indices have potential predictive value for thrombotic complications in ECMO-supported patients and may aid in clinical risk assessment.

关键词

体外膜肺氧合 / 血栓并发症 / 中性粒细胞 / 中性粒细胞胞外诱捕网

Key words

ECMO / Thromboembolic complications / Neutrophils / NETs

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基金资助

内蒙古医学科学院公立医院科研联合基金科技项目(2023GLLH0104)