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Neutrophil extracellular traps are increased after extracorporeal membrane oxygenation support initiation and present in thrombus: A preclinical study using sheep as an animal model

  • Author Footnotes
    1 These authors have contributed equally to this work.
    Yang Zhang
    Footnotes
    1 These authors have contributed equally to this work.
    Affiliations
    Department of Laboratory Medicine, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, No.167, Beilishi Road, Xicheng District, Beijing 100037, China
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  • Author Footnotes
    1 These authors have contributed equally to this work.
    Rui Peng
    Footnotes
    1 These authors have contributed equally to this work.
    Affiliations
    Department of Laboratory Medicine, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, No.167, Beilishi Road, Xicheng District, Beijing 100037, China

    Center of Clinical Laboratory, Beijing Friendship Hospital, Capital Medical University, Beijing, China
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  • Shengqiang Pei
    Affiliations
    Department of Laboratory Medicine, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, No.167, Beilishi Road, Xicheng District, Beijing 100037, China
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  • Sizhe Gao
    Affiliations
    Department of Cardiopulmonary Bypass, State Key Laboratory of Cardiovascular Medicine, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
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  • Yang Sun
    Affiliations
    Department of Laboratory Medicine, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, No.167, Beilishi Road, Xicheng District, Beijing 100037, China
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  • Gaowa Cheng
    Affiliations
    Department of Laboratory Medicine, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, No.167, Beilishi Road, Xicheng District, Beijing 100037, China
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  • Dongze Yu
    Affiliations
    Department of Laboratory Medicine, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, No.167, Beilishi Road, Xicheng District, Beijing 100037, China
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  • Ximing Wang
    Affiliations
    Department of Laboratory Medicine, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, No.167, Beilishi Road, Xicheng District, Beijing 100037, China
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  • Zhangwei Gao
    Affiliations
    Department of Laboratory Medicine, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, No.167, Beilishi Road, Xicheng District, Beijing 100037, China
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  • Bingyang Ji
    Correspondence
    Corresponding authors.
    Affiliations
    Department of Cardiopulmonary Bypass, State Key Laboratory of Cardiovascular Medicine, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
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  • Zhou Zhou
    Correspondence
    Corresponding authors.
    Affiliations
    Department of Laboratory Medicine, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, No.167, Beilishi Road, Xicheng District, Beijing 100037, China
    Search for articles by this author
  • Author Footnotes
    1 These authors have contributed equally to this work.
Published:November 05, 2022DOI:https://doi.org/10.1016/j.thromres.2022.10.019

      Abstract

      Background

      The balance between thrombosis and hemostasis is a difficult issue during extracorporeal membrane oxygenation (ECMO) support. The pathogenesis leading to thrombotic complications during ECMO support is not well understood. Neutrophil extracellular traps (NETs) were reported to participate in thrombosis and have a key role in inflammation. This study aimed to explore the role of NETs in thrombosis during ECMO support and investigate NETs as a predictive biomarker for thrombotic complications during ECMO assistance.

      Methods

      Ten ovine models of ECMO support were established. Animals were then randomly divided into 2 groups (5 sheep/group): venoarterial (VA) ECMO group and venovenous (VV) ECMO group. The venous blood samples were collected at different time points. Markers of NETs were detected in plasma, neutrophils, and thrombi from the vessels and membrane. Moreover, circulating NETs levels in 8 adults treated in the intensive care unit (ICU) who received VA-ECMO and 8 healthy controls were detected; patient survival was also recorded.

      Results

      In vivo study showed that neutrophils and NETs markers (dsDNA and citH3) levels were significantly elevated 6 h after ECMO compared to baseline. Isolated neutrophils from fresh blood at 6 h could release more NETs. dsDNA and citH3 levels were significantly higher in the VA mode than in the VV mode. NETs were found in thrombi from the vessel and membrane. Clinical data further revealed that dsDNA, citH3, and nucleosomes were higher in patients who received ECMO than in healthy controls.

      Conclusions

      These data suggest NETs might be associated with thrombus during ECMO support, especially in the VA mode. These findings provide new insight into preventing thrombotic complications by targeting NETs. Also, NETs may potentially become an early warning biomarker for thrombosis under ECMO assistance.

      Keywords

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