Seattle Children's Hospital, Seattle, WA, USA; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA.
Thromb Res. 2022 Mar;211:154-160. doi: 10.1016/j.thromres.2022.02.011. Epub 2022 Feb 12.
Extracorporeal membrane oxygenation (ECMO) can be life-saving, but suffers from thrombus formation in the circuit with associated risks of oxygenator occlusion, hemolysis and arterial embolism. The formation of thrombin is the key step to thrombus formation and two factors are needed for sustained thrombin generation, a coagulation activator to initiate the process and a procoagulant phospholipid surface for the coagulation system to assemble on.
The purpose of this study was to use thrombin generation potential (TGP) and other assays to determine the specific coagulation activators and sources of procoagulant phospholipid that are present in ECMO patient plasma. Samples were collected from 60 patients on ECMO (age 1d-19y) followed evaluation of native and stimulated TGP, measurement of factor II levels and determination of procoagulant extracellular vesicle levels by flow cytometry.
During ECMO, native (unstimulated) TGP was increased, followed by a decrease back towards normal after ECMO ended. The main activator of TGP in ECMO plasma was increased FXIa (100% of samples tested), while increased tissue factor activity was present in 7%. Procoagulant phospholipids were present in plasma from ECMO patients in the form of circulating platelet and red cell extracellular vesicles, which were increased 2 to 7-fold compared to normal. Procoagulant extracellular vesicle levels correlated with increased plasma native TGP activity.
ECMO activates coagulation in plasma primarily through activation of the contact system and formation of activated factor XIa and generation of circulating procoagulant extracellular vesicles through platelet and red cell activation.
体外膜肺氧合(ECMO)可以救命,但会在体外循环中形成血栓,从而带来氧合器堵塞、溶血和动脉栓塞等相关风险。血栓形成的关键步骤是凝血酶的形成,持续生成凝血酶需要两个因素,即启动过程的凝血激活剂和凝血系统组装的促凝磷脂表面。
本研究旨在使用凝血酶生成潜力(TGP)和其他检测方法来确定 ECMO 患者血浆中存在的特定凝血激活剂和促凝磷脂来源。从 60 名 ECMO 患者(年龄 1 天至 19 岁)中采集样本,随后评估天然和刺激的 TGP、测量因子 II 水平,并通过流式细胞术测定促凝细胞外囊泡水平。
在 ECMO 过程中,天然(未刺激)TGP 增加,随后在 ECMO 结束后恢复正常。ECMO 血浆中 TGP 的主要激活剂是增加的 FXIa(测试的 100%样本),而 7%存在增加的组织因子活性。促凝磷脂以循环血小板和红细胞细胞外囊泡的形式存在于 ECMO 患者的血浆中,与正常相比增加了 2 至 7 倍。促凝细胞外囊泡水平与增加的血浆天然 TGP 活性相关。
ECMO 通过接触系统的激活以及激活的因子 XIa 的形成和血小板及红细胞激活导致的循环促凝细胞外囊泡的生成,主要在血浆中激活凝血。