Early outcomes with utilization of tissue plasminogen activator in COVID-19–associated respiratory distress: A series of five cases

Abstract

BACKGROUND Coronavirus patients demonstrate varying degrees of respiratory insufficiency; many will progress to respiratory failure with a severe version of acute respiratory distress syndrome refractory to traditional supportive strategies. Providers must consider alternative therapies to deter or prevent the cascade of decompensation to fulminant respiratory failure. METHODS This is a case-series of five COVID-19 positive patients who demonstrated severe hypoxemia, declining respiratory performance, and escalating oxygen requirements. Patients met the following criteria: COVID-19 positivity, worsening respiratory performance, severe hypoxemia (Pao 2 ≤ 80) despite traditional supportive measures, escalating supplemental oxygen requirements, and D-dimer greater than 1.5 μg/mL. All patients received protocol directed thrombolytic therapy with tissue plasminogen activator (tPA). RESULTS All five patients improved without deleterious effects of thrombolytic therapy. Patient one was on maximum ventilator support, paralytics, and prone positioning without improvement. During tPA administration his Pao 2/FIO2 ratio improved from 69 to 127. Ventilator support was weaned immediately on posttreatment day 1, and he was extubated on posttreatment day 12. Our second through fifth patients were not intubated at time of initiation of tPA therapy. These patients each required significant oxygen supplementation trending toward intubation. After tPA therapy, all patients demonstrated a noticeable increase in Pao 2 values overtime. Three of these patients avoided intubation due to COVID-19–associated respiratory failure. CONCLUSION Administration of thrombolytics was followed by overall improvement in patients' oxygen requirements, and in three cases, prevented progression to mechanical ventilation, without deleterious effects. Clinical trials of thrombolytic therapy would further serve to underscore the efficacy and utility of this therapy. LEVEL OF EVIDENCE Case series of therapeutic effect, Level V.

COVID-19-associated coagulopathy and disseminated intravascular coagulation

“…Treatment of existing fibrin, which interferes with pulmonary circulation, using a fibrinolytic drug is expected to improve thrombotic conditions. In fact, systemic administration of the fibrinolytic drug tissue-type plasminogen activator (tPA) to ARDS in COVID-19 has been attempted and appears effective in some cases [ 88 – 90 ].…”

Incidence and determinants of high-sensitivity troponin and natriuretic peptides elevation at admission in hospitalized COVID-19 pneumonia patients

“…However, several hypotheses could be made to explain our observations. PaO2/FIO2 ratio is a key parameter for defining acute respiratory distress syndrome [28] and in patients with COVID-19 pneumonia has been used as marker of disease severity [27] as well as end point in studies testing novel treatments [29]. Additionally, PaO2/ FIO2 may decrease with higher oxygen consumption and lower cardiac output [30]: both elements can contribute to myocardial injury.…”

Perspective on fibrinolytic therapy in COVID-19: the potential of inhalation therapy against suppressed-fibrinolytic-type DIC

“…Some articles suggest several treatment options using fibrinolytic drugs for acute respiratory distress syndrome (ARDS) in severe cases of COVID-19 [1][2][3][4]. ARDS and organ dysfunction associated with a cytokine storm have been identified as causes of death in COVID-19 [5].…”

“…Although heparin is frequently used to remedy the thrombotic pathology in COVID-19, pulmonary embolism is still seen in approximately 20% of severe cases, and there is disagreement regarding the intensity of anticoagulant therapy. Besides heparin, the thrombotic condition might be improved by using fibrinolytic drugs to degrade pre-existing fibrin in the lung [1][2][3][4]. The fibrinolytic drug, tissue-type plasminogen activator (tPA), has been systemically administered to treat ARDS in COVID-19 and appeared to be effective in some patients [2][3][4].…”

“…Besides heparin, the thrombotic condition might be improved by using fibrinolytic drugs to degrade pre-existing fibrin in the lung [1][2][3][4]. The fibrinolytic drug, tissue-type plasminogen activator (tPA), has been systemically administered to treat ARDS in COVID-19 and appeared to be effective in some patients [2][3][4]. Since tPA has been reported to show an antiinflammatory effect in addition to a fibrinolytic action, this potential of tPA would be helpful for improving the prognosis of COVID-19 patients [11,12].…”