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体外膜肺氧合相关凝血功能障碍的多模态特征分析。

Multi-Modal Characterization of the Coagulopathy Associated With Extracorporeal Membrane Oxygenation.

机构信息

Department of Anesthesiology and Intensive Care Medicine, University Hospital Tübingen, Tübingen, Germany.

Department of Anesthesiology, Intensive Care, and Pain Medicine, BG-Trauma Center Tübingen, Tübingen, Germany.

出版信息

Crit Care Med. 2020 May;48(5):e400-e408. doi: 10.1097/CCM.0000000000004286.

Abstract

OBJECTIVES

Extracorporeal membrane oxygenation is used to stabilize severe cardiocirculatory and/or respiratory failure. However, extracorporeal membrane oxygenation is associated with a coagulopathy characterized by thromboembolic and hemorrhagic complications. This study aimed to characterize the pathomechanism of the extracorporeal membrane oxygenation-associated coagulopathy and identify options to optimize its monitoring and therapy.

DESIGN

Prospective observational clinical trial.

SETTING

ICU of a university hospital.

PATIENTS

Patients treated with venovenous extracorporeal membrane oxygenation (n = 10) due to acute respiratory distress syndrome and patients treated with venoarterial extracorporeal membrane oxygenation (n = 8) due to cardiocirculatory failure. One patient per group (venovenous extracorporeal membrane oxygenation or venoarterial extracorporeal membrane oxygenation) had surgery before extracorporeal membrane oxygenation.

INTERVENTIONS

Blood was sampled before, and 1, 24, and 48 hours after extracorporeal membrane oxygenation implantation. Point-of-care tests (thrombelastometry/platelet aggregometry), conventional coagulation tests, whole blood counts, and platelet flow cytometry were performed.

MEASUREMENTS AND MAIN RESULTS

Even before extracorporeal membrane oxygenation, plasmatic coagulation and platelet aggregation were impaired due to systemic inflammation, liver failure, anticoagulants (heparins, phenprocoumon, apixaban), and antiplatelet medication. During extracorporeal membrane oxygenation, hemodilution and contact of blood components with artificial surfaces and shear stress inside extracorporeal membrane oxygenation additionally contributed to coagulation and platelet defects. Fibrinogen levels, fibrin polymerization, platelet activation, and microparticle release were increased in venovenous extracorporeal membrane oxygenation compared to venoarterial extracorporeal membrane oxygenation patients. Point-of-care results were available faster than conventional analyses. Bleeding requiring blood product application occurred in three of 10 venovenous extracorporeal membrane oxygenation patients and in four of eight venoarterial extracorporeal membrane oxygenation patients. No thrombotic events were observed. In-hospital mortality was 30% for venovenous extracorporeal membrane oxygenation and 37.5% for venoarterial extracorporeal membrane oxygenation patients.

CONCLUSIONS

The extracorporeal membrane oxygenation-associated coagulopathy is a multifactorial and quickly developing syndrome. It is characterized by individual changes of coagulation parameters and platelets and is aggravated by anticoagulants. The underlying factors of the extracorporeal membrane oxygenation-associated coagulopathy differ between venovenous extracorporeal membrane oxygenation and venoarterial extracorporeal membrane oxygenation patients and are best diagnosed by a combination of point-of-care and conventional coagulation and platelet analyses. Therapy protocols for treating extracorporeal membrane oxygenation-associated coagulopathy should be further validated in large-scale prospective clinical investigations.

摘要

目的

体外膜肺氧合用于稳定严重的心循环和/或呼吸衰竭。然而,体外膜肺氧合与凝血功能障碍有关,其特征为血栓栓塞和出血并发症。本研究旨在描述体外膜肺氧合相关凝血功能障碍的发病机制,并确定优化其监测和治疗的选择。

设计

前瞻性观察性临床试验。

地点

大学医院的 ICU。

患者

因急性呼吸窘迫综合征接受静脉-静脉体外膜肺氧合(n = 10)治疗的患者和因心循环衰竭接受静脉-动脉体外膜肺氧合(n = 8)治疗的患者。每组各有一名患者(静脉-静脉体外膜肺氧合或静脉-动脉体外膜肺氧合)在体外膜肺氧合前接受手术。

干预措施

在体外膜肺氧合植入前、植入后 1、24 和 48 小时采集血液样本。进行即时检测(血栓弹力描记术/血小板聚集测定)、常规凝血试验、全血细胞计数和血小板流式细胞术。

测量和主要结果

即使在体外膜肺氧合之前,由于全身炎症、肝功能衰竭、抗凝剂(肝素、苯丙香豆素、阿哌沙班)和抗血小板药物,血浆凝血和血小板聚集已受损。在体外膜肺氧合期间,血液稀释以及血液成分与人工表面的接触和体外膜肺氧合内的剪切应力进一步导致凝血和血小板缺陷。与静脉-动脉体外膜肺氧合患者相比,静脉-静脉体外膜肺氧合患者的纤维蛋白原水平、纤维蛋白聚合、血小板活化和微颗粒释放增加。即时检测结果比常规分析更快可用。在 10 名静脉-静脉体外膜肺氧合患者中有 3 名和 8 名静脉-动脉体外膜肺氧合患者中有 4 名出现需要血液制品应用的出血。未观察到血栓形成事件。静脉-静脉体外膜肺氧合患者的院内死亡率为 30%,静脉-动脉体外膜肺氧合患者的院内死亡率为 37.5%。

结论

体外膜肺氧合相关凝血功能障碍是一种多因素且迅速发展的综合征。其特点是凝血参数和血小板的个体变化,并因抗凝剂而加重。静脉-静脉体外膜肺氧合和静脉-动脉体外膜肺氧合患者的体外膜肺氧合相关凝血功能障碍的基础因素不同,通过即时检测和常规凝血及血小板分析的联合检测可最佳诊断。体外膜肺氧合相关凝血功能障碍的治疗方案应在大规模前瞻性临床研究中进一步验证。

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