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Enhanced Procoagulant Activity on Blood Cells after Acute Ischemic Stroke

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Abstract

The role of phosphatidylserine (PS)-mediated procoagulant activity (PCA) in stroke remains unclear. To ascertain this role, early dynamic evolution of PS exposure on blood cells and released microparticles (MPs) and the corresponding PCA were evaluated in patients with acute ischemic stroke (AIS). Flow cytometry analyses revealed that initial levels of PS exposure on erythrocyte, platelet, and leukocyte were 2.40-, 1.36-, and 1.38-fold higher, respectively, in AIS than the risk factor-matched (RF) controls. Concomitantly, total PS+ MPs were increased in AIS (1949 ± 483/μl) compared with the RF group (1674 ± 387/μl; P = 0.019) and healthy controls (1052 ± 179/μl; P < 0.001). Specifically, PS+ erythrocytes gradually increased within 1 week. PS+ platelets and MPs peaked at 24 h and declined at 7 days, while PS+ leukocytes were markedly elevated at 24 h. Further, PS exposure on blood cells and MPs in stroke resulted in shortened clotting time with an accompanying increase in FXa and thrombin formation significantly. Treatment with lactadherin, a PS antagonist, delayed the coagulation time by approximately 20 % and blocked the generation of FXa and thrombin by about 50 %. Furthermore, initial counts of PS+ platelets and platelet MPs significantly correlated with stroke severity. Thrombin generation promoted by platelets and MPs at 12 h was significantly higher in patients with cardioembolism than in patients without. The thrombophilic susceptibility of AIS patients can be partly ascribed to PS exposure on blood cells and the release of MPs. Our studies identify PS exposure as a potentially novel therapeutic target in the treatment of AIS.

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Authors and Affiliations

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

    Zhipeng Yao, Xiaoming Wu, Lu Zhao, Li Guo, Dongxia Tong, Xiaoyan Yang, Ruijuan Deng, Jialan Shi & Jin Zhou

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

    Lixiu Wang, Zengxiang Dong, Yayan Bi & Ye Tian

  3. Department of Neurology, the Fourth Hospital, Harbin Medical University, Harbin, China

    Chunling Chi

  4. Department of Research, Brigham and Women’s Hospital, Harvard Medical School, VA Boston Healthcare System, Boston, MA, USA

    Valerie A. Novakovic

  5. Department of Surgery, Brigham and Women’s Hospital, Harvard Medical School, VA Boston Healthcare System, Boston, MA, USA

    Hemant S Thatte & Jialan Shi

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

    Junjie Kou

  7. Department of Neurosurgery, the Second Hospital, Harbin Medical University, Harbin, China

    Shaoshan Hu

Authors
  1. Zhipeng Yao
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  2. Lixiu Wang
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  3. Xiaoming Wu
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  4. Lu Zhao
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  5. Chunling Chi
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  6. Li Guo
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  7. Dongxia Tong
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  8. Xiaoyan Yang
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  9. Zengxiang Dong
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  10. Ruijuan Deng
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  11. Valerie A. Novakovic
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  12. Hemant S Thatte
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  13. Yayan Bi
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  14. Ye Tian
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  15. Jialan Shi
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  16. Jin Zhou
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  17. Junjie Kou
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  18. Shaoshan Hu
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Corresponding authors

Correspondence to Jialan Shi, Jin Zhou, Junjie Kou or Shaoshan Hu.

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Funding

This work was supported by grants from the National Natural Science Foundation of China (81270588, 81470301, 81670128, 81670298, and 61575058), Natural Science Foundation of Heilongjiang Province (ZD2015020), and Graduate Innovation Fund of Harbin Medical University (YJSCX2015-56HYD).

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Approval

All procedures performed in this study 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.

Informed Consent

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

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Yao, Z., Wang, L., Wu, X. et al. Enhanced Procoagulant Activity on Blood Cells after Acute Ischemic Stroke. Transl. Stroke Res. 8, 83–91 (2017). https://doi.org/10.1007/s12975-016-0501-7

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  • DOI: https://doi.org/10.1007/s12975-016-0501-7

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