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. 2025 Jan 6;26(1):4.
doi: 10.1186/s40360-024-00806-x.

Effects of different antiplatelet therapy drugs on platelet activation and platelet-leukocyte aggregate formation in early septic ARDS

Lu Wang  1 , Liang-Yu Mi  1 , Xiang-Yu Chen  1 , Huai-Wu He  1 , Yun Long  2
Affiliations

Effects of different antiplatelet therapy drugs on platelet activation and platelet-leukocyte aggregate formation in early septic ARDS

Lu Wang et al. BMC Pharmacol Toxicol. .

Abstract

Background: In patients with sepsis, platelets are activated and adhere to neutrophils, forming platelet-leukocyte aggregates (PLAs) that lead to the development of MODS. ARDS is one of the main manifestations of septic MODS. We designed this study to explore the effects of different anti-plate therapy drugs on platelet activation and platelet-leukocyte aggregate (PLA) formation in the early stage of septic ARDS.

Methods: Sixty adult male SD rats were randomly divided into: Control group; ARDS group, ARDS + aspirin group, ARDS + clopidogrel group and ARDS + tirofiban group. ARDS was performed via instill lipopolysaccharide (LPS) intratracheally at a dose of 5 mg/kg. Aspirin or clopidogrel were given by gavage immediately after modeling. Tirofiban were given by intraperitoneal injection immediately after modeling. Rats in every group were euthanized by rapid decapitation 6 h after modeling. Platelet activation and PLA were assessed using flow cytometry and immunofluorescence staining. Histology of lung was performed by hematoxylin and eosin staining.

Results: Aspirin, clopidogrel and tirofiban decreased CRP, IL-1 and TNF-α significantly in septic ARDS (P < 0.05). Aspirin, clopidogrel and tirofiban decreased platelet function and ratio of wet/dry significantly in septic ARDS (P < 0.05). Aspirin, clopidogrel and tirofiban increased PaO2 significantly in septic ARDS (P < 0.05). Platelet activation and PLA in the ARDS + aspirin group, ARDS + clopidogrel group and ARDS + tirofiban group decreased significantly compared to the ARDS group (P < 0.05). At 6 h after ARDS operation, obvious histological damage was observed in the lungs. All of these histological changes were quantitatively evaluated using injury scores. Aspirin, clopidogrel and tirofiban reduced the histological damages in ARDS group (P < 0.05).

Conclusions: Aspirin, clopidogrel and tirofiban alleviated the inflammatory response and pulmonary edema, reduced platelet function, and alleviated hypoxemia in early septic ARDS. Aspirin, clopidogrel and tirofiban reduced platelet activation and PLA formation in early septic ARDS. Aspirin, clopidogrel and tirofiban ultimately alleviated lung injury in early septic ARDS.

Keywords: ARDS; Aspirin; Clopidogrel; Platelet-leukocyte aggregate; Sepsis; Tirofiban.

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Conflict of interest statement

Declarations. Ethics approval: This study was approved by the Institutional Animal Care and Use Committee (IACUC) at Peking Union Medical College, Beijing, China. (IACUC protocol number: XHDW-2023-029). Consent for publication: All authors have agreed to publish it. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Inflammatory cytokines, platelet function, wet/dry, and PaO2. Results are presented as mean ± SD (n = 12). a = P < 0.05 compared to the Control group, b = P < 0.05 compared to the ARDS group
Fig. 2
Fig. 2
Platelet activation and platelet-leukocyte aggregate (PLA) in the peripheral blood. Results are presented as mean ± SD (n = 12). a = P < 0.05 compared to the Control group, b = P < 0.05 compared to the ARDS group
Fig. 3
Fig. 3
Platelet-leukocyte aggregate (PLA) in the lung. Scale bars: 20 μm. Results are presented as mean ± SD (n = 12). a = P < 0.05 compared to the Control group, b = P < 0.05 compared to the ARDS group
Fig. 4
Fig. 4
Histopathological scores of the lung. Scale bars: 100 μm. Results are presented as mean ± SD (n = 12). a = P < 0.05 compared to the Control group, b = P < 0.05 compared to the ARDS group
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