Fibrinolysis as a Causative Mechanism for Bleeding Complications on Extracorporeal Membrane Oxygenation: A Pilot Observational Prospective Study.

IF 9.1 1区医学 Q1 ANESTHESIOLOGY Anesthesiology Pub Date : 2024-07-01 DOI:10.1097/ALN.0000000000004980

Julie Helms, Anaïs Curtiaud, François Severac, Marine Tschirhart, Hamid Merdji, Matthieu Bourdin, Geneviève Contant, François Depasse, Ramy Abou Rjeily, Laurent Sattler, Ferhat Meziani, Eduardo Angles-Cano

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Abstract

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.

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纤溶作为 ECMO 出血并发症的致病机制：一项前瞻性试点观察研究。

背景：体外膜肺氧合（ECMO）与出血并发症的高风险相关。ECMO 对纤维蛋白溶解的具体影响仍有待研究。本试验性前瞻性观察研究的目的是调查 ECMO 患者出血事件中纤维蛋白溶解标志物的纵向动态变化，即随时间推移而发生的变化：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剂 [t-PA]、纤溶酶原激活剂抑制剂-1 [PAI-1]、它们的复合物 [t-PA-PAI-1]）的纵向动态变化、在植入前、植入后 0、6 和 12 小时以及之后的每天，对接受静脉和静脉-动脉 ECMO 的患者的组织型纤溶酶原激活剂 [t-PA-PAI-1]、纤溶酶原-抗纤溶酶原复合物、纤溶酶原和 D-二聚体）进行了测量。结果组群包括 30 名患者（214 个 ECMO 日）。与正常值相比，t-PA、D-二聚体、凝血酶-抗凝血酶复合物、PAI-1 和 t-PA-PAI-1 复合物的浓度升高，而纤溶酶原的浓度降低。值得注意的是，出血和非出血患者之间存在差异：出血患者的 D-二聚体、凝血酶原-抗凝血酶、t-PA、PAI-1 和 t-PA-PAI-1 在出血前呈上升趋势，随后降至基线水平；相反，非出血患者的这些指标呈下降趋势。此外，与非出血患者相比，出血患者的 D-二聚体和 t-PA 呈上升趋势（D-二聚体动态中位值：1080 vs. -440 ng/mL，p=0.05；t-PA 动态中位值：0.130 vs. 0.100 nM，p=0.038），并且这两种标记物在出血前一天显著增加。t-PA浓度超过0.304 nM与出血事件有关（OR 4.92，95% CI [1.01-24.08]，p=0.049）：结论：接触性激活可诱导 ECMO 患者，尤其是出血患者发生纤溶。这一发现支持了这一机制作为 ECMO 期间出血的可能致病因素的作用，并为新的治疗前景开辟了新途径：由于多种因素，体外膜肺氧合（ECMO）与出血并发症的高风险相关。虽然导致 ECMO 期间纤维蛋白溶解的原因有多种，但他们的研究表明，出血患者的接触性激活增加，可能会受益于通过这种途径抑制止血激活的新型治疗药物。

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来源期刊

Anesthesiology 医学-麻醉学

CiteScore

10.40

自引率

5.70%

发文量

542

审稿时长

3-6 weeks

期刊介绍： With its establishment in 1940, Anesthesiology has emerged as a prominent leader in the field of anesthesiology, encompassing perioperative, critical care, and pain medicine. As the esteemed journal of the American Society of Anesthesiologists, Anesthesiology operates independently with full editorial freedom. Its distinguished Editorial Board, comprising renowned professionals from across the globe, drives the advancement of the specialty by presenting innovative research through immediate open access to select articles and granting free access to all published articles after a six-month period. Furthermore, Anesthesiology actively promotes groundbreaking studies through an influential press release program. The journal's unwavering commitment lies in the dissemination of exemplary work that enhances clinical practice and revolutionizes the practice of medicine within our discipline.