Venous thrombosis epidemiology, pathophysiology, and anticoagulant therapies and trials in severe acute respiratory syndrome coronavirus 2 infection

Obi, Andrea T.; Barnes, Geoffrey D.; Napolitano, Lena M.; Henke, Peter K.; Wakefield, Thomas W.

OBJECTIVE: Infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus confers a risk of significant coagulopathy, with the resulting development of venous thromboembolism (VTE), potentially contributing to the morbidity and mortality. The purpose of the present review was to evaluate the potential mechanisms that contribute to this increased risk of coagulopathy and the role of anticoagulants in treatment. METHODS: A literature review of coronavirus disease 2019 (COVID-19) and/or SARS-CoV-2 and cell-mediated inflammation, clinical coagulation abnormalities, hypercoagulability, pulmonary intravascular coagulopathy, and anticoagulation was performed. The National Clinical Trials database was queried for ongoing studies of anticoagulation and/or antithrombotic treatment or the incidence or prevalence of thrombotic events in patients with SARS-CoV-2 infection. RESULTS: The reported rate of VTE among critically ill patients infected with SARS-CoV-2 has been 21% to 69%. The phenomenon of breakthrough VTE, or the acute development of VTE despite adequate chemoprophylaxis or treatment dose anticoagulation, has been shown to occur with severe infection. The pathophysiology of overt hypercoagulability and the development of VTE is likely multifactorial, with evidence supporting the role of significant cell-mediated responses, including neutrophils and monocytes/macrophages, endothelialitis, cytokine release syndrome, and dysregulation of fibrinolysis. Collectively, this inflammatory process contributes to the severe pulmonary pathology experienced by patients with COVID-19. As the infection worsens, extreme D-dimer elevations, significant thrombocytopenia, decreasing fibrinogen, and prolongation of prothrombin time and partial thromboplastin time occur, often associated with deep vein thrombosis, in situ pulmonary thrombi, and/or pulmonary embolism. A new phenomenon, termed pulmonary intravascular coagulopathy, has been associated with morbidity in patients with severe infection. Heparin, both unfractionated heparin and low-molecular-weight heparin, have emerged as agents that can address the viral infection, inflammation, and thrombosis in this syndrome. CONCLUSIONS: The overwhelming inflammatory response in patients with SARS-CoV-2 infection can lead to a hypercoagulable state, microthrombosis, large vessel thrombosis, and, ultimately, death. Early VTE prophylaxis should be provided to all admitted patients. Therapeutic anticoagulation therapy might be beneficial for critically ill patients and is the focus of 39 ongoing trials. Close monitoring for thrombotic complications is imperative, and, if confirmed, early transition from prophylactic to therapeutic anticoagulation should be instituted. The interplay between inflammation and thrombosis has been shown to be a hallmark of the SARS-CoV-2 viral infection.