Is there a role for tissue plasminogen activator (tPA) as a novel treatment for refractory COVID-19 associated acute respiratory distress syndrome (ARDS)?

• Main Authors: Barrett, Christopher D. (Author), Yaffe, Michael B. (Author)
• Other Authors: Massachusetts Institute of Technology. Department of Biological Engineering (Contributor), Massachusetts Institute of Technology. Department of Biology (Contributor)
• Format: Article
• Language: English
• Published: Ovid Technologies (Wolters Kluwer Health), 2020-04-27T20:22:34Z.
• Subjects: Article
• Online Access: Get fulltext

 The global pandemic of COVID-19 has begun to oversaturate the world's medical capacity to accommodate a large surge of patients with acute respiratory distress syndrome (ARDS). Acute respiratory distress syndrome has no effective treatment besides supportive care, with the use of ventilatory strategies encompassing low tidal volumes that limit transpulmonary pressures being the mainstay. A consistent finding in ARDS is the deposition of fibrin in the airspaces and lung parenchyma, along with fibrin-platelet microthrombi in the pulmonary vasculature, which contribute to the development of progressive respiratory dysfunction and right heart failure. Similar pathologic findings have now been observed in lung specimens from patients infected with COVID-19. This physiologically destructive activation of the clotting system in ARDS results from enhanced activation and propagation of clot formation together with suppression of fibrinolysis, and is thought to be mediated by dysfunction of the pulmonary endothelium in the case of influenza A. Targeting the coagulation and fibrinolytic systems to improve the treatment of ARDS has been proposed since at least 2003. In particular, the use of plasminogen activators to limit ARDS progression and reduce ARDS-induced death has received strong support from animal models and a phase 1 human clinical trial. In 2001, Hardaway and colleagues showed that administration of either urokinase or streptokinase to patients with terminal ARDS reduced the expected mortality from 100% to 70% with no adverse bleeding events. Importantly, the majority of patients who ultimately succumbed died from renal or hepatic failure, rather than pulmonary failure. [First paragraph] ©2020