Fibrinolytic therapy for refractory COVID-19 acute respiratory distress syndrome: Scientific rationale and review

Abstract

The coronavirus disease 2019 (COVID-19) pandemic has caused respiratory failure and associated mortality in numbers that have overwhelmed global health systems. Thrombotic coagulopathy is present in nearly three quarters of patients with COVID-19 admitted to the intensive care unit, and both the clinical picture and pathologic findings are consistent with microvascular occlusive phenomena being a major contributor to their unique form of respiratory failure. Numerous studies are ongoing focusing on anticytokine therapies, antibiotics, and antiviral agents, but none to date have focused on treating the underlying thrombotic coagulopathy in an effort to improve respiratory failure in COVID-19. There are animal data and a previous human trial demonstrating a survival advantage with fibrinolytic therapy to treat acute respiratory distress syndrome. Here, we review the extant and emerging literature on the relationship between thrombotic coagulopathy and pulmonary failure in the context of COVID-19 and present the scientific rationale for consideration of targeting the coagulation and fibrinolytic systems to improve pulmonary function in these patients.

Keywords: COVID‐19; acute respiratory distress syndrome; fibrinolysis; pulmonary failure; tissue plasminogen activator.

Figure 1

Pharmacokinetic simulations of t‐PA levels over time relative to its native inhibitor (PAI‐1) in patients with COVID‐19 based on various body mass and bolus/maintenance doses of t‐PA. The model assumes a plasma clearance of 8.3 min, and a terminal half‐life of 88 min. ⁸² PAI‐1, plasminogen activator inhibitor‐1; t‐PA, tissue‐type plasminogen activator

Figure 2

Possible algorithm for consideration of fibrinolytic therapy in severe, medically refractory COVID‐19 respiratory failure. COVID‐19, coronavirus disease 2019; MI, myocardial infarction; t‐PA, tissue‐type plasminogen activator inhibitor‐1