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Intravascular cells and circulating microparticles induce procoagulant activity via phosphatidylserine exposure in heart failure

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Abstract

Relatively little information is known about the definitive role of phosphatidylserine (PS) in the hypercoagulability of heart failure (HF). Our objectives were to assess the levels of PS exposure on microparticles (MPs) and blood cells (BCs) in each group of HF patients and to evaluate their procoagulant activity (PCA). HF patients in each NYHA functional class II–IV (II n = 30, III n = 30, IV n = 30) and healthy controls (n = 25) were enrolled in the present study. PS exposure on MPs, BCs was analyzed with flow cytometry. MPs were classified based on their cellular origin: platelets (CD41a+), neutrophils (CD66b+), endothelial cells (CD31+CD41a−), erythrocytes (CD235a+), monocytes (CD14+), T lymphocytes (CD3+), and B lymphocytes (CD19+). PCA was evaluated by clotting time, extrinsic/intrinsic FXa and prothrombinase production assays, as well as fibrin formation assays. Inhibition assays of PCA of PS+ BCs and MPs were performed by lactadherin. There was no significant difference in MP cellular origin between healthy and HF subjects. However, the total number of PS+ MPs was significantly increased in HF patients compared with healthy controls. In addition, circulating PS+ BCs cooperated with PS+ MPs to markedly shorten coagulation time and dramatically increase FXa/thrombin generation and fibrin formation in each HF group. Moreover, blockade of exposed PS on BCs and MPs with lactadherin inhibited PCA by approximately 80%. Our results lead us to believe that exposing PS on the injured BCs and MPs played a pivotal role in the hypercoagulability state in HF patients.

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Acknowledgements

We are grateful to all the patients for their participation in the investigation, staff for excellent technical assistance and the sample collection. The authors are fully responsible for the study design, data collection, analysis and interpretation of the data, and writing of the manuscript. All authors agreed to submit the manuscript for publication.

Funding

This work was supported by grants from the National Natural Science Foundation of China (Grant Nos. 81470301, 81670128, 81873433).

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Authors and Affiliations

  1. Department of Cardiology of the First Hospital, Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin, China

    Yan Kou, Zengxiang Dong, Yayan Bi & Lu Fu

  2. Department of Cardiology of the Second Hospital, Harbin Medical University, Harbin, China

    Lili Zou, Ruipeng Liu, Xinyi Zhao, Ying Wang & Junjie Kou

  3. Department of Ultrasonography of the First Hospital, Harbin Medical University, Harbin, China

    Cong Zhang

  4. Department of Hematology of the First Hospital, Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin, 150001, China

    Jialan Shi

  5. Departments of Research and Surgery, VA Boston Healthcare System, Brigham and Women’s Hospital, Harvard Medical School, 1400 VFW Parkway, West Roxbury, Boston, MA, USA

    Jialan Shi

Authors
  1. Yan Kou
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  2. Lili Zou
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  3. Ruipeng Liu
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  4. Xinyi Zhao
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  6. Cong Zhang
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  8. Junjie Kou
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  9. Yayan Bi
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  10. Lu Fu
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Contributions

YK conceived and designed the study, analyzed the data, made the figures and wrote the manuscript. LZ, RL, XZ, YW, CZ and ZD conducted the assays and contributed to data acquisition. JK and YB designed the study. LF and JS, designed the study, provide the patient samples and revised the manuscript.

Corresponding authors

Correspondence to Lu Fu or Jialan Shi.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Kou, Y., Zou, L., Liu, R. et al. Intravascular cells and circulating microparticles induce procoagulant activity via phosphatidylserine exposure in heart failure. J Thromb Thrombolysis 48, 187–194 (2019). https://doi.org/10.1007/s11239-019-01889-8

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