SARS-CoV-2 infection induces soluble platelet activation markers and PAI-1 in the early moderate stage of COVID-19
SARS-CoV-2 infection induces soluble platelet activation markers and PAI-1 in the early moderate stage of COVID-19
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DOI：
10.1111/ijlh.13829
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发表时间：
2022-03-09
影响因子：
3
通讯作者：
Ahmad, Firdos
中科院分区：
文献类型：
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作者：
Al-Tamimi, Abaher O.;Yusuf, Ayesha M.;Ahmad, Firdos
凝血功能障碍和血栓栓塞是重症COVID-19的重要合并症因素。然而，目前尚不清楚在COVID-19发病过程中，血小板活化标志物和凝血因子何时出现异常。在这里，我们试图评估COVID-19中重度阶段的凝血和血小板激活标志物水平，以了解其发病机制。方法为了解这一点，招募住院的COVID-19患者（需重症监护的重症病例）或非肺炎（中度病例）。采用凝血酶原时间（PT）、活化部分凝血活素时间（APTT）、d -二聚体和组织因子途径抑制剂（TFPI）等基本凝血试验进行表型和分子表征。采用基于流式细胞术的多重检测方法评估FXI、抗凝血酶、凝血酶原、纤维蛋白原、FXIII、p -选择素、sCD40L、纤溶酶原、组织纤溶酶原激活剂（tPA）、纤溶酶原激活剂抑制剂-1 （PAI-1）和d -二聚体。结果在中度COVID-19患者中，血浆p -选择素和CD40配体（sCD40L）均有诱导作用，随着病情的加重，血浆p -选择素和CD40配体明显消失。此外，血浆组织因子途径抑制剂（TFPI）和FXIII水平显著降低，特别是在重症COVID-19患者中。进一步分析显示，中度和重度患者均有纤维蛋白原诱导。有趣的是，在中度COVID-19病例中，PAI-1升高更为明显，而在重度COVID-19病例中，tPA升高尤为明显。特别是，纤维蛋白原和tPA的水平与疾病的严重程度直接相关。综上所述，可溶性p选择素、sCD40L、纤维蛋白原和PAI-1的诱导表明，在COVID-19患者需要重症监护前的中期，血小板和凝血系统被激活。这些发现将有助于设计更好的血栓预防措施，以限制COVID-19的严重程度。
Introduction Coagulation dysfunction and thromboembolism emerge as strong comorbidity factors in severe COVID-19. However, it is unclear when particularly platelet activation markers and coagulation factors dysregulated during the pathogenesis of COVID-19. Here, we sought to assess the levels of coagulation and platelet activation markers at moderate and severe stages of COVID-19 to understand the pathogenesis. Methods To understand this, hospitalized COVID-19 patients with (severe cases that required intensive care) or without pneumonia (moderate cases) were recruited. Phenotypic and molecular characterizations were performed employing basic coagulation tests including prothrombin time (PT), activated partial thromboplastin time (APTT), D-Dimer, and tissue factor pathway inhibitor (TFPI). The flow cytometry-based multiplex assays were performed to assess FXI, anti-thrombin, prothrombin, fibrinogen, FXIII, P-selectin, sCD40L, plasminogen, tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1), and D-Dimer. Results The investigations revealed induction of plasma P-selectin and CD40 ligand (sCD40L) in moderate COVID-19 cases, which were significantly abolished with the progression of COVID-19 severity. Moreover, a profound reduction in plasma tissue factor pathway inhibitor (TFPI) and FXIII were identified particularly in the severe COVID-19. Further analysis revealed fibrinogen induction in both moderate and severe patients. Interestingly, an elevated PAI-1 more prominently in moderate, and tPA particularly in severe COVID-19 cases were observed. Particularly, the levels of fibrinogen and tPA directly correlated with the severity of the disease. Conclusions In summary, induction of soluble P-selectin, sCD40L, fibrinogen, and PAI-1 suggests the activation of platelets and coagulation system at the moderate stage before COVID-19 patients require intensive care. These findings would help in designing better thromboprophylaxis to limit the COVID-19 severity.