Department of Clinical and Biological Sciences, Turin University, 10043 Orbassano, Turin, Italy.
Int J Mol Sci. 2021 Dec 20;22(24):13638. doi: 10.3390/ijms222413638.
COVID-19 infection is associated with a broad spectrum of presentations, but alveolar capillary microthrombi have been described as a common finding in COVID-19 patients, appearing as a consequence of a severe endothelial injury with endothelial cell membrane disruption. These observations clearly point to the identification of a COVID-19-associated coagulopathy, which may contribute to thrombosis, multi-organ damage, and cause of severity and fatality. One significant finding that emerges in prothrombotic abnormalities observed in COVID-19 patients is that the coagulation alterations are mainly mediated by the activation of platelets and intrinsically related to viral-mediated endothelial inflammation. Beyond the well-known role in hemostasis, the ability of platelets to also release various potent cytokines and chemokines has elevated these small cells from simple cell fragments to crucial modulators in the blood, including their inflammatory functions, that have a large influence on the immune response during infectious disease. Indeed, platelets are involved in the pathogenesis of acute lung injury also by promoting NET formation and affecting vascular permeability. Specifically, the deposition by activated platelets of the chemokine platelet factor 4 at sites of inflammation promotes adhesion of neutrophils on endothelial cells and thrombogenesis, and it seems deeply involved in the phenomenon of vaccine-induced thrombocytopenia and thrombosis. Importantly, the hyperactivated platelet phenotype along with evidence of cytokine storm, high levels of P-selectin, D-dimer, and, on the other hand, decreased levels of fibrinogen, von Willebrand factor, and thrombocytopenia may be considered suitable biomarkers that distinguish the late stage of COVID-19 progression in critically ill patients.
COVID-19 感染表现多样，但肺泡毛细血管微血栓已被描述为 COVID-19 患者的常见表现，其出现是由于严重的内皮损伤导致内皮细胞膜破裂。这些观察结果清楚地表明存在 COVID-19 相关的凝血异常，这可能导致血栓形成、多器官损伤，并导致疾病的严重程度和死亡率增加。在 COVID-19 患者中观察到的血栓形成异常的一个重要发现是，凝血改变主要是由血小板激活介导的，与病毒介导的内皮炎症密切相关。血小板除了在止血方面的众所周知的作用外，其释放各种强效细胞因子和趋化因子的能力已将这些小细胞从简单的细胞碎片提升为血液中的关键调节剂，包括其炎症功能，这对传染病期间的免疫反应有很大影响。事实上，血小板通过促进 NET 形成和影响血管通透性，也参与急性肺损伤的发病机制。具体来说，激活的血小板在炎症部位沉积趋化因子血小板因子 4，促进中性粒细胞在内皮细胞上的黏附和血栓形成，并且似乎深深涉及到疫苗引起的血小板减少症和血栓形成现象。重要的是，高活性血小板表型以及细胞因子风暴、高水平 P-选择素、D-二聚体的证据，另一方面，纤维蛋白原、血管性血友病因子和血小板减少的水平降低，可能被认为是区分危重症 COVID-19 患者疾病晚期的合适生物标志物。
