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Fibrinolytic abnormalities in acute respiratory distress syndrome (ARDS) and versatility of thrombolytic drugs to treat COVID-19.
Whyte, Claire S; Morrow, Gael B; Mitchell, Joanne L; Chowdary, Pratima; Mutch, Nicola J.
  • Whyte CS; Aberdeen Cardiovascular & Diabetes Centre, School of Medicine, Medical Sciences and Nutrition, Aberdeen, UK.
  • Morrow GB; Aberdeen Cardiovascular & Diabetes Centre, School of Medicine, Medical Sciences and Nutrition, Aberdeen, UK.
  • Mitchell JL; Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
  • Chowdary P; Institute of Cardiovascular and Metabolic Sciences, School of Biological Sciences, University of Reading, Reading, UK.
  • Mutch NJ; Katharine Dormandy Haemophilia and Thrombosis Centre Royal Free Hospital, London, UK.
J Thromb Haemost ; 18(7): 1548-1555, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-116254
Semantic information from SemMedBD (by NLM)
1. Fibrinolytic Agents TREATS COVID-19
Subject
Fibrinolytic Agents
Predicate
TREATS
Object
COVID-19
2. Critical Illness PROCESS_OF Patients
Subject
Critical Illness
Predicate
PROCESS_OF
Object
Patients
3. COVID-19 COEXISTS_WITH Respiratory Distress Syndrom
Subject
COVID-19
Predicate
COEXISTS_WITH
Object
Respiratory Distress Syndrom
4. Respiration PROCESS_OF Patients
Subject
Respiration
Predicate
PROCESS_OF
Object
Patients
5. cytokine INTERACTS_WITH Leukocytes
Subject
cytokine
Predicate
INTERACTS_WITH
Object
Leukocytes
6. Lung LOCATION_OF cytokine
Subject
Lung
Predicate
LOCATION_OF
Object
cytokine
7. Parenchyma PART_OF Lung
Subject
Parenchyma
Predicate
PART_OF
Object
Lung
8. COVID-19 PROCESS_OF Patients
Subject
COVID-19
Predicate
PROCESS_OF
Object
Patients
9. Lung PART_OF Patients
Subject
Lung
Predicate
PART_OF
Object
Patients
10. Epithelium PART_OF Lung
Subject
Epithelium
Predicate
PART_OF
Object
Lung
11. Alveolar Epithelial Cells PART_OF Endothelium
Subject
Alveolar Epithelial Cells
Predicate
PART_OF
Object
Endothelium
12. Epithelium LOCATION_OF Plasminogen Activator Inhibitor 1
Subject
Epithelium
Predicate
LOCATION_OF
Object
Plasminogen Activator Inhibitor 1
13. Endothelial Cells LOCATION_OF Plasminogen Activator Inhibitor 1
Subject
Endothelial Cells
Predicate
LOCATION_OF
Object
Plasminogen Activator Inhibitor 1
14. Alveolar Epithelial Cells LOCATION_OF Thromboplastin
Subject
Alveolar Epithelial Cells
Predicate
LOCATION_OF
Object
Thromboplastin
15. Lung LOCATION_OF Fibrin
Subject
Lung
Predicate
LOCATION_OF
Object
Fibrin
16. Fibrin AUGMENTS Fibrinolysis
Subject
Fibrin
Predicate
AUGMENTS
Object
Fibrinolysis
17. alteplase TREATS Respiratory Distress Syndrom
Subject
alteplase
Predicate
TREATS
Object
Respiratory Distress Syndrom
18. alteplase ASSOCIATED_WITH Croupous bronchitis
Subject
alteplase
Predicate
ASSOCIATED_WITH
Object
Croupous bronchitis
19. Plasminogen Activator TREATS COVID-19
Subject
Plasminogen Activator
Predicate
TREATS
Object
COVID-19
20. Plasminogen Activator TREATS Patients
Subject
Plasminogen Activator
Predicate
TREATS
Object
Patients
21. Alveolar ventilation function PROCESS_OF Patients
Subject
Alveolar ventilation function
Predicate
PROCESS_OF
Object
Patients
22. Fibrinolytic Agents TREATS COVID-19
Subject
Fibrinolytic Agents
Predicate
TREATS
Object
COVID-19
23. Critical Illness PROCESS_OF Patients
Subject
Critical Illness
Predicate
PROCESS_OF
Object
Patients
24. COVID-19 COEXISTS_WITH Respiratory Distress Syndrome, Adult
Subject
COVID-19
Predicate
COEXISTS_WITH
Object
Respiratory Distress Syndrome, Adult
25. Respiration PROCESS_OF Patients
Subject
Respiration
Predicate
PROCESS_OF
Object
Patients
26. cytokine INTERACTS_WITH Leukocytes
Subject
cytokine
Predicate
INTERACTS_WITH
Object
Leukocytes
27. Lung LOCATION_OF cytokine
Subject
Lung
Predicate
LOCATION_OF
Object
cytokine
28. Parenchyma PART_OF Lung
Subject
Parenchyma
Predicate
PART_OF
Object
Lung
29. COVID-19 PROCESS_OF Patients
Subject
COVID-19
Predicate
PROCESS_OF
Object
Patients
30. Lung PART_OF Patients
Subject
Lung
Predicate
PART_OF
Object
Patients
31. Epithelium PART_OF Lung
Subject
Epithelium
Predicate
PART_OF
Object
Lung
32. Alveolar Epithelial Cells PART_OF Endothelium
Subject
Alveolar Epithelial Cells
Predicate
PART_OF
Object
Endothelium
33. Epithelium LOCATION_OF Plasminogen Activator Inhibitor 1
Subject
Epithelium
Predicate
LOCATION_OF
Object
Plasminogen Activator Inhibitor 1
34. Endothelial Cells LOCATION_OF Plasminogen Activator Inhibitor 1
Subject
Endothelial Cells
Predicate
LOCATION_OF
Object
Plasminogen Activator Inhibitor 1
35. Alveolar Epithelial Cells LOCATION_OF Thromboplastin
Subject
Alveolar Epithelial Cells
Predicate
LOCATION_OF
Object
Thromboplastin
36. Lung LOCATION_OF Fibrin
Subject
Lung
Predicate
LOCATION_OF
Object
Fibrin
37. Fibrin AUGMENTS Fibrinolysis
Subject
Fibrin
Predicate
AUGMENTS
Object
Fibrinolysis
38. alteplase TREATS Respiratory Distress Syndrome, Adult
Subject
alteplase
Predicate
TREATS
Object
Respiratory Distress Syndrome, Adult
39. alteplase ASSOCIATED_WITH Croupous bronchitis
Subject
alteplase
Predicate
ASSOCIATED_WITH
Object
Croupous bronchitis
40. Plasminogen Activator TREATS COVID-19
Subject
Plasminogen Activator
Predicate
TREATS
Object
COVID-19
41. Plasminogen Activator TREATS Patients
Subject
Plasminogen Activator
Predicate
TREATS
Object
Patients
42. Alveolar ventilation function PROCESS_OF Patients
Subject
Alveolar ventilation function
Predicate
PROCESS_OF
Object
Patients
ABSTRACT
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.
Subject(s)
Keywords

Full text: Available Collection: International databases Database: MEDLINE Main subject: Pneumonia, Viral / Thrombolytic Therapy / Tissue Plasminogen Activator / Coronavirus Infections / Fibrinolysis / Fibrinolytic Agents / Betacoronavirus Type of study: Diagnostic study / Randomized controlled trials Limits: Humans Language: English Journal: J Thromb Haemost Journal subject: Hematology Year: 2020 Document Type: Article Affiliation country: Jth.14872

Full text: Available Collection: International databases Database: MEDLINE Main subject: Pneumonia, Viral / Thrombolytic Therapy / Tissue Plasminogen Activator / Coronavirus Infections / Fibrinolysis / Fibrinolytic Agents / Betacoronavirus Type of study: Diagnostic study / Randomized controlled trials Limits: Humans Language: English Journal: J Thromb Haemost Journal subject: Hematology Year: 2020 Document Type: Article Affiliation country: Jth.14872