Fibrinolysis as a Novel Therapy in COVID-19
Other therapies targeting coagulation are being examined regarding their potential therapeutic utility in COVID-19, including fibrinolytic agents such as tPA (tissue-type plasminogen activator). tPA converts the inactive enzyme plasminogen to plasmin leading to the subsequent breakdown of cross-linked fibrin. The interest in tPA has emerged from the concept that ARDS is characterized by significant local inflammatory reaction in addition to a hypofibrinolytic state. As discussed previously, severe COVID-19 can result in ARDS, which promotes mass upregulation of inflammatory cytokines and leukocytes, and can result in extensive thrombin generation, fibrin formation, and microvascular thrombosis.155
The use of systemic tPA in preclinical and human models of ARDS demonstrates improved oxygenation, and a case report of tPA use in severe COVID-19 showed an initial improvement in oxygenation during tPA infusion, but this effect was lost after tPA therapy ceased.156–158 However, the benefits of tPA may be offset by the considerable risk of major bleeding seen in nonstroke clinical trials,159 which has led to the consideration of nebulized therapy to increase local concentrations and reduce systemic coagulation effects. Recent clinical trial data suggest that, in severe ARDS, nebulized fibrinolytic therapy is associated with improved oxygenation and ventilatory parameters, which may be another plausible treatment option in COVID-19.155