Anticoagulation Strategies in Adults Undergoing Extracorporeal Membrane Oxygenation: A Systematic Review and Meta-Analysis

IF 2.2 3区医学 Q3 ENGINEERING, BIOMEDICAL

Artificial organs Pub Date : 2026-08-08 Epub Date: 2026-05-20 DOI:10.1111/aor.70162

Vincenz Scharner, Karoline Lenz, Harald Herkner, Nina Buchtele, Thomas Staudinger, Eva Schaden, Marion Wiegele, Johannes Gratz

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引用次数: 0

Abstract

Background

Extracorporeal membrane oxygenation (ECMO) is a life-saving intervention for patients with severe cardiac or respiratory failure, but it is associated with a high risk of thrombotic and bleeding complications. Unfractionated heparin (UFH) remains the most frequently used anticoagulant, largely due to historical practice and longstanding clinical familiarity, despite the absence of robust evidence from randomized controlled trials. Alternative strategies—including direct thrombin inhibitors (DTIs), low-molecular-weight heparins (LMWHs), nafamostat mesylate (NM), and no anticoagulation—are increasingly being explored. However, a comprehensive and contemporary comparison of these approaches has been lacking.

Methods

We conducted a comprehensive search of PubMed/MEDLINE, EMBASE, and CENTRAL through March 2025, supplemented by manual searches of reference lists. We included randomized controlled trials and observational studies including patients 16 years or older receiving ECMO for ≥ 24 h that compared any anticoagulation strategy with another or with no anticoagulation. The primary outcome was thromboembolic events; secondary outcomes included bleeding and mortality. Risk of bias was assessed using validated tools. Meta-analyses were performed using a multivariable random-effects model, with prespecified subgroup analyses by ECMO modality (venoarterial [VA], venovenous [VV], or mixed) and subsequent sensitivity analyses.

Results

Twenty-one observational studies involving 2 775 adult ECMO patients were included, with UFH serving as the comparator in all studies. DTIs showed reduced thromboembolism (OR 0.73; 95% CI: 0.53–0.99) and were associated with significantly lower bleeding (OR 0.51; 95% CI: 0.39–0.67) and mortality (OR 0.70; 95% CI: 0.52–0.94), confirmed in a sensitivity analysis. LMWH was associated with significantly reduced odds of thromboembolic events (OR 0.26; 95% CI: 0.13–0.55), as well as showing a favorable bleeding profile (OR 0.46; 95% CI: 0.25–0.87), yet no significant difference in mortality (OR 0.80; 95% CI: 0.30–2.14). While no anticoagulation reduced the odds for bleeding (OR 0.17; 95% CI: 0.07–0.38) and NM showed no significant differences, both had wide confidence intervals, limiting interpretation. Heterogeneity for LMWH was low for efficacy and bleeding, yet substantial for mortality; for DTI, low to moderate; for no anticoagulation, low; and for NM, substantial to high on all comparisons.

Conclusions

In this systematic review and meta-analysis, DTIs and LMWH appear to be effective and safe alternatives to UFH in adult ECMO, with consistent reductions in thromboembolic and bleeding events and a survival benefit observed for DTIs. These findings support reconsideration of UFH as the default anticoagulant and favor a more prominent role for alternative strategies in clinical practice.

Trial Registration

PROSPERO CRD42022363588

查看原文本刊更多论文

接受体外膜氧合的成人抗凝策略：系统回顾和荟萃分析。

背景：体外膜氧合（ECMO）是一种挽救严重心脏或呼吸衰竭患者生命的干预措施，但它与血栓和出血并发症的高风险相关。尽管缺乏随机对照试验的有力证据，但未分离肝素（UFH）仍然是最常用的抗凝剂，这主要是由于历史实践和长期临床熟悉。替代策略——包括直接凝血酶抑制剂（DTIs）、低分子肝素（LMWHs）、甲磺酸那莫他酯（NM）和无抗凝——正在被越来越多地探索。然而，缺乏对这些方法进行全面和当代的比较。方法：到2025年3月，我们对PubMed/MEDLINE、EMBASE和CENTRAL进行了全面检索，并辅以人工检索参考文献列表。我们纳入了随机对照试验和观察性研究，包括16岁或以上接受ECMO≥24小时的患者，将任何抗凝策略与另一种抗凝策略或无抗凝策略进行比较。主要结局是血栓栓塞事件；次要结局包括出血和死亡率。使用经过验证的工具评估偏倚风险。采用多变量随机效应模型进行meta分析，并通过ECMO模式（静脉动脉[VA]、静脉静脉[VV]或混合）进行预先指定的亚组分析和随后的敏感性分析。结果：纳入21项观察性研究，涉及2775例成人ECMO患者，所有研究均以UFH作为比较物。在敏感性分析中证实，dti可减少血栓栓塞（OR 0.73; 95% CI: 0.53-0.99），并与出血（OR 0.51; 95% CI: 0.39-0.67）和死亡率（OR 0.70; 95% CI: 0.52-0.94）的显著降低相关。低分子肝素显著降低了血栓栓塞事件的发生率（OR 0.26; 95% CI: 0.13-0.55），并显示出良好的出血情况（OR 0.46; 95% CI: 0.25-0.87），但死亡率无显著差异（OR 0.80; 95% CI: 0.30-2.14）。虽然无抗凝降低了出血的几率（OR 0.17; 95% CI: 0.07-0.38）和NM没有显着差异，但两者都有很宽的置信区间，限制了解释。低分子肝素的疗效和出血异质性低，但死亡率显著；对于DTI，低至中等；对于无抗凝作用的，低；对于NM来说，在所有比较中都是相当高的。结论：在这项系统回顾和荟萃分析中，DTIs和低分子肝素似乎是成人ECMO中UFH的有效和安全的替代方案，DTIs的血栓栓塞和出血事件持续减少，并且观察到DTIs的生存获益。这些发现支持重新考虑UFH作为默认抗凝剂，并支持在临床实践中替代策略发挥更突出的作用。试验注册：PROSPERO CRD42022363588。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Artificial organs 工程技术-工程：生物医学

CiteScore

4.30

自引率

12.50%

发文量

303

审稿时长

4-8 weeks

期刊介绍： Artificial Organs is the official peer reviewed journal of The International Federation for Artificial Organs (Members of the Federation are: The American Society for Artificial Internal Organs, The European Society for Artificial Organs, and The Japanese Society for Artificial Organs), The International Faculty for Artificial Organs, the International Society for Rotary Blood Pumps, The International Society for Pediatric Mechanical Cardiopulmonary Support, and the Vienna International Workshop on Functional Electrical Stimulation. Artificial Organs publishes original research articles dealing with developments in artificial organs applications and treatment modalities and their clinical applications worldwide. Membership in the Societies listed above is not a prerequisite for publication. Articles are published without charge to the author except for color figures and excess page charges as noted.