Procoagulant platelets regulate H1N1-induced thrombosis formation

doi:10.3969/j.issn.1674-8115.2026.01.003

Abstract

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.

Key words: platelet, procoagulant platelet, thrombosis, infection

CLC Number:

R364

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.

Figures/Tables 4

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References 39

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