MUlticenter STudy of tissue plasminogen activator (alteplase) use in COVID‐19 severe respiratory failure (MUST COVID): A retrospective cohort study
BACKGROUND: Few therapies exist to treat severe COVID-19 respiratory failure once it develops. Given known diffuse pulmonary microthrombi on autopsy studies of COVID-19 patients, we hypothesized that tissue plasminogen activator (tPA) may improve pulmonary function in COVID-19 respiratory failure. M...
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| Format: | Article |
| Language: | English |
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Wiley
2023
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| Online Access: | https://hdl.handle.net/1721.1/147027 |
| _version_ | 1826195348086849536 |
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| author | Yaffe, Michael Barrett, Christopher |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Yaffe, Michael Barrett, Christopher |
| author_sort | Yaffe, Michael |
| collection | MIT |
| description | BACKGROUND: Few therapies exist to treat severe COVID-19 respiratory failure once it develops. Given known diffuse pulmonary microthrombi on autopsy studies of COVID-19 patients, we hypothesized that tissue plasminogen activator (tPA) may improve pulmonary function in COVID-19 respiratory failure. METHODS: A multicenter, retrospective, observational study of patients with confirmed COVID-19 and severe respiratory failure who received systemic tPA (alteplase) was performed. Seventy-nine adults from seven medical centers were included in the final analysis after institutional review boards' approval; 23 were excluded from analysis because tPA was administered for pulmonary macroembolism or deep venous thrombosis. The primary outcome was improvement in the PaO2/FiO2 ratio from baseline to 48 h after tPA. Linear mixed modeling was used for analysis. RESULTS: tPA was associated with significant PaO2/FiO2 improvement at 48 h (estimated paired difference = 23.1 ± 6.7), which was sustained at 72 h (interaction term p < 0.00). tPA administration was also associated with improved National Early Warning Score 2 scores at 24, 48, and 72 h after receiving tPA (interaction term p = 0.00). D-dimer was significantly elevated immediately after tPA, consistent with lysis of formed clot. Patients with declining respiratory status preceding tPA administration had more marked improvement in PaO2/FiO2 ratios than those who had poor but stable (not declining) respiratory status. There was one intracranial hemorrhage, which occurred within 24 h following tPA administration. CONCLUSIONS: These data suggest tPA is associated with significant improvement in pulmonary function in severe COVID-19 respiratory failure, especially in patients whose pulmonary function is in decline, and has an acceptable safety profile in this patient population. |
| first_indexed | 2024-09-23T10:11:16Z |
| format | Article |
| id | mit-1721.1/147027 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T10:11:16Z |
| publishDate | 2023 |
| publisher | Wiley |
| record_format | dspace |
| spelling | mit-1721.1/1470272023-01-10T03:37:09Z MUlticenter STudy of tissue plasminogen activator (alteplase) use in COVID‐19 severe respiratory failure (MUST COVID): A retrospective cohort study Yaffe, Michael Barrett, Christopher Massachusetts Institute of Technology. Department of Biology Massachusetts Institute of Technology. Department of Biological Engineering BACKGROUND: Few therapies exist to treat severe COVID-19 respiratory failure once it develops. Given known diffuse pulmonary microthrombi on autopsy studies of COVID-19 patients, we hypothesized that tissue plasminogen activator (tPA) may improve pulmonary function in COVID-19 respiratory failure. METHODS: A multicenter, retrospective, observational study of patients with confirmed COVID-19 and severe respiratory failure who received systemic tPA (alteplase) was performed. Seventy-nine adults from seven medical centers were included in the final analysis after institutional review boards' approval; 23 were excluded from analysis because tPA was administered for pulmonary macroembolism or deep venous thrombosis. The primary outcome was improvement in the PaO2/FiO2 ratio from baseline to 48 h after tPA. Linear mixed modeling was used for analysis. RESULTS: tPA was associated with significant PaO2/FiO2 improvement at 48 h (estimated paired difference = 23.1 ± 6.7), which was sustained at 72 h (interaction term p < 0.00). tPA administration was also associated with improved National Early Warning Score 2 scores at 24, 48, and 72 h after receiving tPA (interaction term p = 0.00). D-dimer was significantly elevated immediately after tPA, consistent with lysis of formed clot. Patients with declining respiratory status preceding tPA administration had more marked improvement in PaO2/FiO2 ratios than those who had poor but stable (not declining) respiratory status. There was one intracranial hemorrhage, which occurred within 24 h following tPA administration. CONCLUSIONS: These data suggest tPA is associated with significant improvement in pulmonary function in severe COVID-19 respiratory failure, especially in patients whose pulmonary function is in decline, and has an acceptable safety profile in this patient population. 2023-01-09T18:52:33Z 2023-01-09T18:52:33Z 2022 2023-01-09T18:45:17Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/147027 Yaffe, Michael and Barrett, Christopher. 2022. "MUlticenter STudy of tissue plasminogen activator (alteplase) use in COVID‐19 severe respiratory failure (MUST COVID): A retrospective cohort study." Research and Practice in Thrombosis and Haemostasis, 6 (2). en 10.1002/RTH2.12669 Research and Practice in Thrombosis and Haemostasis Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Wiley Elsevier |
| spellingShingle | Yaffe, Michael Barrett, Christopher MUlticenter STudy of tissue plasminogen activator (alteplase) use in COVID‐19 severe respiratory failure (MUST COVID): A retrospective cohort study |
| title | MUlticenter STudy of tissue plasminogen activator (alteplase) use in COVID‐19 severe respiratory failure (MUST COVID): A retrospective cohort study |
| title_full | MUlticenter STudy of tissue plasminogen activator (alteplase) use in COVID‐19 severe respiratory failure (MUST COVID): A retrospective cohort study |
| title_fullStr | MUlticenter STudy of tissue plasminogen activator (alteplase) use in COVID‐19 severe respiratory failure (MUST COVID): A retrospective cohort study |
| title_full_unstemmed | MUlticenter STudy of tissue plasminogen activator (alteplase) use in COVID‐19 severe respiratory failure (MUST COVID): A retrospective cohort study |
| title_short | MUlticenter STudy of tissue plasminogen activator (alteplase) use in COVID‐19 severe respiratory failure (MUST COVID): A retrospective cohort study |
| title_sort | multicenter study of tissue plasminogen activator alteplase use in covid 19 severe respiratory failure must covid a retrospective cohort study |
| url | https://hdl.handle.net/1721.1/147027 |
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