Covid-19 associated acute respiratory distress syndrome, treated with tissue plasminogen activator, as a compassionate salvage therapy

Introduction: The association of diffuse pulmonary micro and macro thrombi is well established in acute respiratory distress syndrome (ARDS). Similar pathological findings are observed in COVID-19 related pulmonary injury. Herein, we present a COVID-19 induced respiratory failure case, treated with unconventional tissue plasminogen activator (tPA) infusion therapy, which led to remarkable hypoxemia improvement. Case description: 53-year-old male, a former smoker, presented with fever, cough, and shortness of breath. He tested positive for COVID-19 and was found to have bilateral lower lobe consolidation on Chest CT and elevated inflammatory markers. The patient was started on therapeutic anticoagulation with enoxaparin. The patient was hypoxic, requiring 6 liters oxygen supplementation via nasal cannula initially, but on day 9, he developed worsening hypoxic respiratory failure requiring 100 % High-flow nasal cannula (HFNC) oxygen supplementation without significant change in radiological findings compared to prior imaging. A spike in D dimer levels was appreciated as well, from 2600 to 10,000 ng/mL. The decision was made to administer tPA 25 mg over 2 hours, followed by a 25 mg tPA infusion administered over the next 22 hours. Therapeutic enoxaparin was restarted afterwards. His oxygenation status improved after the bolus dose and required 50 % HFNC. On day 2 of administration, the patient's hypoxemia dramatically improved, and the patient was saturating 96% with 3 liters of oxygen supplementation. Discussion: Our patient developed refractory hypoxemia which couldn't be explained by radiographic findings and combined with a spike in D dimer, suggested a high thrombotic burden in the pulmonary circulation which prompted us to consider low dose tPA as a salvage therapy. Dramatic improvement of hypoxemia post tPA administration confirmed our suspicion. Multiple case series in mechanically ventilated and non-mechanically ventilated patients with COVID-19 associated ARDS, have shown mortality benefit after tPA infusion. However not commonly used in view of the potential adverse effect of life-threatening bleed. Our case highlights the fact that, in spite of absence of randomized evidence, tPA may be used as a compassionate salvage therapy, if no contraindications exist.