Strasbourg University (UNISTRA); Strasbourg University Hospital, Medical Intensive Care Unit (NHC), Strasbourg, France; INSERM (French National Institute of Health and Medical Research), Unit 1260, Regenerative Nanomedicine, Medicine Federation of Strasbourg, Strasbourg, France.
Strasbourg University Hospital, Clinical Research Methods Group (GMRC), Strasbourg, France.
Anesthesiology. 2024 Jul 1;141(1):75-86. doi: 10.1097/ALN.0000000000004980.
BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is associated with a high risk of bleeding complications. The specific impact of ECMO on fibrinolysis remains unexplored. The objective of the current pilot observational prospective study was to investigate the longitudinal dynamics of fibrinolytic markers-i.e., changes over time-in the context of bleeding events in patients on ECMO. METHODS: Longitudinal dynamics of contact phase components (kininogen and bradykinin) and fibrinolysis markers (tissue plasminogen activator [tPA], plasminogen activator inhibitor-1 [PAI-1], their complexes [tPA•PAI-1], plasmin-antiplasmin complexes, plasminogen, and D-dimer) were measured in patients undergoing venovenous and venoarterial ECMO, before implantation, at 0, 6, and 12 h after implantation, and daily thereafter. RESULTS: The cohort consisted of 30 patients (214 ECMO days). The concentrations of tPA, D-dimer, plasmin-antiplasmin complexes, PAI-1, and tPA•PAI-1 complexes were increased, whereas plasminogen decreased compared to normal values. A noteworthy divergence was observed between hemorrhagic and nonhemorrhagic patients: in bleeding patients, D-dimer, plasmin-antiplasmin, tPA, PAI-1, and tPA•PAI-1 followed an increasing kinetics before hemorrhage and then decreased to their baseline level; conversely, nonbleeding patients showed a decreasing kinetics in these markers. Also, D-dimer and tPA followed an increasing kinetics in bleeding patients compared to nonbleeding patients (median values for D-dimer dynamics: 1,080 vs. -440 ng/ml, P = 0.05; tPA dynamics: 0.130 vs. 0.100 nM, P = 0.038), and both markers significantly increased the day before hemorrhage. A tPA concentration above 0.304 nM was associated with bleeding events (odds ratio, 4.92; 95% CI, 1.01 to 24.08; P = 0.049). CONCLUSIONS: Contact activation induces fibrinolysis in ECMO patients, especially in patients experiencing bleeding. This finding supports the role of this mechanism as a possible causal factor for hemorrhages during ECMO and open new avenues for novel therapeutic perspectives.
背景：体外膜肺氧合（ECMO）会导致严重出血并发症。ECMO 对纤溶的具体影响仍不清楚。本前瞻性观察性研究的目的是在 ECMO 患者发生出血事件的情况下，研究纤溶标志物（即随时间变化的标志物）的纵向动力学。
方法：对接受静脉-静脉和静脉-动脉 ECMO 的患者，在植入前、植入后 0、6 和 12 小时以及此后每天测量接触相成分（激肽原和缓激肽）和纤溶标志物（组织型纤溶酶原激活物 [tPA]、纤溶酶原激活物抑制剂-1 [PAI-1]、它们的复合物 [tPA•PAI-1]、纤溶酶-抗纤溶酶复合物、纤溶酶原和 D-二聚体）的纵向动力学。
结果：该队列包括 30 名患者（214 ECMO 天）。与正常值相比，tPA、D-二聚体、纤溶酶-抗纤溶酶复合物、PAI-1 和 tPA•PAI-1 复合物的浓度升高，而纤溶酶原降低。出血患者和非出血患者之间观察到显著的差异：在出血患者中，D-二聚体、纤溶酶-抗纤溶酶、tPA、PAI-1 和 tPA•PAI-1 复合物在出血前呈增加趋势，然后降至基线水平；相反，非出血患者的这些标志物呈下降趋势。此外，与非出血患者相比，出血患者的 D-二聚体和 tPA 呈增加趋势（D-二聚体动力学中位数：1080 对-440ng/ml，P=0.05；tPA 动力学中位数：0.130 对 0.100nM，P=0.038），且两种标志物在出血前一天均显著升高。tPA 浓度大于 0.304nM 与出血事件相关（比值比，4.92；95%CI，1.01 至 24.08；P=0.049）。
结论：接触激活在 ECMO 患者中诱导纤溶，特别是在发生出血的患者中。这一发现支持了这一机制作为 ECMO 期间出血的可能因果因素的作用，并为新的治疗观点开辟了新的途径。
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