Basic research

Procoagulant platelets regulate H1N1-induced thrombosis formation

  • Yin Xuying ,
  • Wang Xuanjia ,
  • Yang Mina ,
  • Jiang Haojie ,
  • Dai Jing ,
  • Sun Xiaoyu ,
  • Xu Yanyan
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  • 1.Department of Biochemistry and Molecular Cell Biology, Shanghai Jiao Tong University College of Basic Medical Sciences, Shanghai 200025, China
    2.Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai 200030, China
    3.Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
    4.College of Health Sciences and Technology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
First author contact:The study was designed by Yin Xuying, Xu Yanyan, Sun Xiaoyu, Dai Jing, and Jiang Haojie. The experiments were conducted by Yin Xuying, Wang Xuanjia, and Yang Mina. The manuscript was drafted and revised by Yin Xuying and Xu Yanyan. All authors have read the final version of the manuscript and consented to its submission.
Xu Yanyan, E-mail: xuyanyan901@163.com
Sun Xiaoyu, E-mail: sunxiaoyu@fudan.edu.cn.

Received date: 2025-08-19

  Accepted date: 2025-10-09

  Online published: 2026-01-30

Supported by

National Key Research and Development Program of China(2023YFC2507801);National Natural Science Foundation of China(82322004);Natural Science Foundation of Shanghai(25ZR1402094)

Abstract

Objective ·To investigate the role of procoagulant platelets in thrombosis induced by H1N1 influenza virus infection in mice. Methods ·A viral infection model was established in mice by intranasal instillation of the H1N1 influenza virus. Body weight was continuously monitored post-infection, and whole blood was collected from the retro-orbital venous plexus to measure platelet counts. Plasma samples were prepared from abdominal aortic blood. Thrombin time (TT), fibrinogen, D-dimer, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) levels were measured by using enzyme-linked immunosorbent assay (ELISA). Lung and liver tissue sections from infected mice were prepared, and hematoxylin-eosin (HE) staining was employed to observe thrombus formation in lung and liver tissues of mice. Tyramide signal amplification (TSA)-based multiplex immunohistochemistry was performed on lung and liver tissues to analyze thrombus composition. Flow cytometry was used to monitor the monocyte-platelet aggregates and the proportion of procoagulant platelets in mice after viral infection. A platelet depletion model was established by tail vein injection of anti-mouse GP1b (R300). Body weight and platelet counts were continuously monitored in infected mice. Plasma TT, fibrinogen, and D-dimer levels were measured to evaluate coagulation function in mice. Results ·Following H1N1 infection, mice exhibited progressive weight loss and abnormal coagulation parameters, including prolonged TT, decreased fibrinogen levels, and elevated D-dimer levels (all P<0.05).Plasma levels of IL-6 and TNF-α were also elevated. HE staining revealed prominent thrombus formation in the pulmonary and hepatic vasculature of infected mice (all P<0.05). Flow cytometry demonstrated a significant increase in the proportion of procoagulant platelets after infection. The proportion of procoagulant platelets showed a positive correlation with viral dose, and was associated with D-dimer levels, fibrinogen levels, and thrombus area (all P<0.05). TSA staining further confirmed that the thrombi primarily consisted of fibrin and procoagulant platelets. Depletion of platelets in mice prior to H1N1 infection markedly reduced thrombosis in lung and liver tissues and alleviated coagulation abnormalities (all P<0.05). Conclusion ·H1N1 virus infection may significantly elevate the proportion of procoagulant platelets in mice, leading to coagulation dysfunction and subsequent thrombosis in multiple tissues.

Cite this article

Yin Xuying , Wang Xuanjia , Yang Mina , Jiang Haojie , Dai Jing , Sun Xiaoyu , Xu Yanyan . Procoagulant platelets regulate H1N1-induced thrombosis formation[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2026 , 46(1) : 25 -33 . DOI: 10.3969/j.issn.1674-8115.2026.01.003

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