NY Cardiovascular Research, New York, NY, USA.
Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Clin Appl Thromb Hemost. 2020 Jan-Dec;26:1076029620936776. doi: 10.1177/1076029620936776.
COVID-19 has proven to be particularly challenging given the complex pathogenesis of SARS-CoV-2. Early data have demonstrated how the host response to this novel coronavirus leads to the proliferation of pro-inflammatory cytokines, massive endothelial damage, and generalized vascular manifestations. While SARS-CoV-2 primarily targets the upper and lower respiratory tract, other organ systems are also affected. SARS-CoV-2 relies on 2 host cell receptors for successful attachment: angiotensin-converting enzyme 2 and transmembrane protease serine 2. Clinicopathologic reports have demonstrated associations between severe COVID-19 and viral coagulopathy, resulting in pulmonary embolism; venous, arterial, and microvascular thrombosis; lung endothelial injury; and associated thrombotic complications leading to acute respiratory distress syndrome. Viral coagulopathy is not novel given similar observations with SARS classic, including the consumption of platelets, generation of thrombin, and increased fibrin degradation product exhibiting overt disseminated intravascular coagulation-like syndrome. The specific mechanism(s) behind the thrombotic complications in COVID-19 patients has yet to be fully understood. Parenteral anticoagulants, such as heparin and low-molecular-weights heparins, are widely used in the management of COVID-19 patients. Beyond the primary (anticoagulant) effects of these agents, they may exhibit antiviral, anti-inflammatory, and cytoprotective effects. Direct oral anticoagulants and antiplatelet agents are also useful in the management of these patients. Tissue plasminogen activator and other fibrinolytic modalities may also be helpful in the overall management. Catheter-directed thrombolysis can be used in patients developing pulmonary embolism. Further investigations are required to understand the molecular and cellular mechanisms involved in the pathogenesis of COVID-19-associated thrombotic complications.
COVID-19 被证明是特别具有挑战性的，因为 SARS-CoV-2 的复杂发病机制。早期数据表明，宿主对这种新型冠状病毒的反应如何导致促炎细胞因子的增殖、大量内皮损伤和广泛的血管表现。虽然 SARS-CoV-2 主要靶向上呼吸道和下呼吸道，但其他器官系统也受到影响。SARS-CoV-2 依赖 2 种宿主细胞受体成功附着：血管紧张素转换酶 2 和跨膜蛋白酶丝氨酸 2。临床病理报告表明，严重 COVID-19 与病毒凝血功能障碍之间存在关联，导致肺栓塞；静脉、动脉和微血管血栓形成；肺内皮损伤；以及相关的血栓并发症导致急性呼吸窘迫综合征。病毒凝血功能障碍并不新鲜，因为与 SARS 经典病例有类似的观察结果，包括血小板消耗、凝血酶生成和纤维蛋白降解产物增加，表现出明显的弥散性血管内凝血样综合征。COVID-19 患者血栓并发症的确切机制尚未完全了解。肝素和低分子量肝素等肠外抗凝剂广泛用于 COVID-19 患者的治疗。除了这些药物的主要（抗凝）作用外，它们还可能具有抗病毒、抗炎和细胞保护作用。直接口服抗凝剂和抗血小板药物在这些患者的治疗中也很有用。组织型纤溶酶原激活剂和其他纤维蛋白溶解方式在整体治疗中也可能有帮助。导管定向溶栓可用于发生肺栓塞的患者。需要进一步研究以了解 COVID-19 相关血栓并发症发病机制中涉及的分子和细胞机制。
