Tissue plasminogen activator (tPA) treatment for COVID‐19 associated acute respiratory distress syndrome (ARDS): A case series

Wang, Janice; Hajizadeh, Negin; Moore, Ernest E.; McIntyre, Robert C.; Moore, Peter K.; Veress, Livia A.; Yaffe, Michael B.; Moore, Hunter B.; Barrett, Christopher D.

doi:10.1111/jth.14828

Cited by 500 publications

(558 citation statements)

References 13 publications

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“…Patients with elevated D-dimer or SIC score had lower mortality when treated with heparin (mostly low molecular weight) compared with those not treated with heparin. A case series of 3 patients with respiratory failure and high D-dimer levels reported transient improvement in respiratory parameters with the use of tissue plasminogen activator [5]. The lung pathology in one COVID-19 patient revealed microvascular thrombosis suggesting that the lung microvascular thrombosis in COVID-19 patients may contribute to respiratory failure and ARDS [5].…”

Section: Coagulopathymentioning

confidence: 99%

COVID-19-Related Stroke

Hess

Eldahshan

Rutkowski

2020

Transl. Stroke Res.

343

330

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The COVID-19 pandemic is associated with neurological symptoms and complications including stroke. There is hypercoagulability associated with COVID-19 that is likely a "sepsis-induced coagulopathy" and may predispose to stroke. The SARS-CoV-2 virus binds to angiotensin-converting enzyme 2 (ACE2) present on brain endothelial and smooth muscle cells. ACE2 is a key part of the renin angiotensin system (RAS) and a counterbalance to angiotensin-converting enzyme 1 (ACE1) and angiotensin II. Angiotensin II is proinflammatory, is vasoconstrictive, and promotes organ damage. Depletion of ACE2 by SARS-CoV-2 may tip the balance in favor of the "harmful" ACE1/angiotensin II axis and promote tissue injury including stroke. There is a rationale to continue to treat with tissue plasminogen activator for COVID-19-related stroke and low molecular weight heparinoids may reduce thrombosis and mortality in sepsis-induced coagulopathy.

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Section: Coagulopathymentioning

confidence: 99%

COVID-19-Related Stroke

Hess

Eldahshan

Rutkowski

2020

Transl. Stroke Res.

343

330

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“…83 The authors suggest that there is a precedent for increasing the dose of the bolus of tPA while maintaining heparin infusion, as the anticoagulant is effective against sub-massive pulmonary embolism. 83,84 In addition to readdressing the fibrinolytic balance, administration of tPA to ARDS patients may confer anti-inflammatory effects, as it has been shown to suppress neutrophil activation in a rat model of ALI induced by IL-1α. 85 A major consideration in anticoagulant or thrombolytic therapy is the undesirable complication of bleeding.…”

Section: Ther Apeuti C Op Ti On S For Ards In Covid -19 Patientsmentioning

confidence: 99%

Fibrinolytic abnormalities in acute respiratory distress syndrome (ARDS) and versatility of thrombolytic drugs to treat COVID‐19

Whyte

Morrow

Mitchell

et al. 2020

Journal of Thrombosis and Haemostasis

246

266

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The global pandemic of coronavirus disease 2019 (COVID-19) is associated with the development of acute respiratory distress syndrome (ARDS), which requires ventilation in critically ill patients. The pathophysiology of ARDS results from acute inflammation within the alveolar space and prevention of normal gas exchange. The increase in proinflammatory cytokines within the lung leads to recruitment of leukocytes, further propagating the local inflammatory response. A consistent finding in ARDS is the deposition of fibrin in the air spaces and lung parenchyma. COVID-19 patients show elevated D-dimers and fibrinogen. Fibrin deposits are found in the lungs of patients due to the dysregulation of the coagulation and fibrinolytic systems. Tissue factor (TF) is exposed on damaged alveolar endothelial cells and on the surface of leukocytes promoting fibrin deposition, while significantly elevated levels of plasminogen activator inhibitor 1 (PAI-1) from lung epithelium and endothelial cells create a hypofibrinolytic state. Prophylaxis treatment of COVID-19 patients with low molecular weight heparin (LMWH) is important to limit coagulopathy. However, to degrade pre-existing fibrin in the lung it is essential to promote local fibrinolysis. In this review, we discuss the repurposing of fibrinolytic drugs, namely tissue-type plasminogen activator (tPA), to treat COVID-19 associated ARDS. tPA is an approved intravenous thrombolytic treatment, and the nebulizer form has been shown to be effective in plastic bronchitis and is currently in Phase II clinical trial. Nebulizer plasminogen activators may provide a targeted approach in COVID-19 patients to degrade fibrin and improving oxygenation in critically ill patients. K E Y W O R D Sfibrin, fibrinolysis, plasminogen activator inhibitor 1, respiratory distress syndrome (adult), SARS virus, tissue plasminogen activatorThis is an open access article under the terms of the Creat ive Commo ns Attri bution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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“…Tissue Plasminogen Activator ARDS with concomitant DIC was observed in 70% of those who die of COVID-19 [97]. There is evidence that fibrin deposition in the pulmonary microvasculature is a contributing factor for ARDS and fibrinolytic therapy was shown to improve survival in ARDS patients.…”

Section: Extracorporeal Membrane Oxygenationmentioning

confidence: 99%

COVID-19 and Cancer: a Comprehensive Review

et al. 2020

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Purpose of Review The outbreak of the novel coronavirus disease 2019 has emerged to be the biggest global health threat worldwide, which has now infected over 1.7 million people and claimed more than 100,000 lives around the world. Under these unprecedented circumstances, there are no well-established guidelines for cancer patients. Recent Findings The risk for serious disease and death in COVID-19 cases increases with advancing age and presence of comorbid health conditions. Since the emergence of the first case in Wuhan, China, in December 2019, tremendous research efforts have been underway to understand the mechanisms of infectivity and transmissibility of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a fatal virus responsible for abysmal survival outcomes. To minimize the mortality rate, it becomes prudent to identify symptoms promptly and employ treatments appropriately. Even though no cure has been established, multiple clinical trials are underway to determine the most optimal strategy. Managing cancer patients under these circumstances is rather challenging, given their vulnerable status and the aggressive nature of their underlying disease. Summary In this comprehensive review, we discuss the impact of COVID-19 on health and the immune system of those affected, reviewing the latest treatment approaches and ongoing clinical trials. Additionally, we discuss challenges faced while treating cancer patients and propose potential approaches to manage this vulnerable population during this pandemic.

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Tissue plasminogen activator (tPA) treatment for COVID‐19 associated acute respiratory distress syndrome (ARDS): A case series

Cited by 500 publications

References 13 publications

COVID-19-Related Stroke

COVID-19-Related Stroke

Fibrinolytic abnormalities in acute respiratory distress syndrome (ARDS) and versatility of thrombolytic drugs to treat COVID‐19

COVID-19 and Cancer: a Comprehensive Review

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