Coagulation Abnormalities and Thrombosis in Patients Infected With SARS-CoV-2 and Other Pandemic Viruses

Abstract

The world is amid a pandemic caused by severe acute respiratory syndrome-coronavirus 2. Severe acute respiratory syndrome-coronavirus causes serious respiratory tract infections that can lead to viral pneumonia, acute respiratory distress syndrome, and death. Some patients with coronavirus disease 2019 (COVID-19) have an activated coagulation system characterized by elevated plasma levels of d-dimer-a biomarker of fibrin degradation. Importantly, high levels of D-dimer on hospital admission are associated with increased risk of mortality. Venous thromboembolism is more common than arterial thromboembolism in hospitalized COVID-19 patients. Pulmonary thrombosis and microvascular thrombosis are observed in autopsy studies, and this may contribute to the severe hypoxia observed in COVID-19 patients. It is likely that multiple systems contribute to thrombosis in COVID-19 patients, such as activation of coagulation, platelet activation, hypofibrinolysis, endothelial cell dysfunction, inflammation, neutrophil extracellular traps, and complement. Targeting these different pathways may reduce thrombosis and improve lung function in COVID-19 patients.

Keywords: coronavirus; fibrin; orthomyxoviridae; pandemics; thrombosis.

Figure.

Potential pathways that drive thrombosis in coronavirus disease 2019 (COVID-19) patients. Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infects lung epithelial cells and endothelial cells (ECs), which leads to the recruitment of a variety of immune cells, such as macrophages and neutrophils. Activated macrophages and ECs contribute to the cytokine storm. EC activation also increases vascular permeability (VP). Neutrophils release neutrophil extracellular traps (NETs). Activated platelets likely contribute to thrombosis and NET formation. TF (tissue factor) expression is likely to be increased in activated epithelial cells, macrophages, and ECs and will activate the coagulation system. Similarly, FXIIa (factor XIIa) can increase coagulation. SARS-CoV-2 infection also activates the fibrinolytic system and may increase PAI-1 (plasminogen activator inhibitor 1), which would reduce fibrin degradation. Finally, the complement system is activated in COVID-19 patients, and cellular damage would increase the activation of the coagulation system.