Fibrinolysis and COVID‐19: A plasmin paradox

Medcalf, Robert L.; Keragala, Charithani B.; Myles, Paul S.

doi:10.1111/jth.14960

Cited by 89 publications

(97 citation statements)

References 38 publications

(76 reference statements)

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“…The reported incidence of VTE in COVID‐19 ranges up to 8% in general wards, up to 35% in the ICU setting, and up to 58% in consecutive autopsies in patients in whom VTE was not suspected before death (reviewed by Marietta et al) 70 . Intriguingly, it has been speculated that in patients with severe/critical COVID‐19 disease there develops a ‘consumptive fibrinolysis’ due to overwhelming levels of fibrin and misfolded proteins/necrotic tissue in the lung, suggesting a clinical paradox where plasmin formation can be either deleterious or beneficial in COVID‐19, but not at the same time 71 . In hospitalized patients with COVID‐19, low molecular weight heparin (preferred) or unfractionated heparin at prophylactic doses for prevention of VTE is recommended by the World Health Organization 72 and several scientific societies (reviewed by Marietta et al) 70 .…”

Section: Obesity and Thrombotic Riskmentioning

confidence: 99%

Obesity: A critical risk factor in the COVID‐19 pandemic

et al. 2020

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Summary Obesity is an emerging independent risk factor for susceptibility to and severity of coronavirus disease 2019 (COVID‐19) caused by the severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2). Previous viral pandemics have shown that obesity, particularly severe obesity (BMI > 40 kg/m2), is associated with increased risk of hospitalization, critical care admission and fatalities. In this narrative review, we examine emerging evidence of the influence of obesity on COVID‐19, the challenges to clinical management from pulmonary, endocrine and immune dysfunctions in individuals with obesity and identify potential areas for further research. We recommend that people with severe obesity be deemed a vulnerable group for COVID‐19; clinical trials of pharmacotherapeutics, immunotherapies and vaccination should prioritize inclusion of people with obesity.

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Section: Obesity and Thrombotic Riskmentioning

confidence: 99%

Obesity: A critical risk factor in the COVID‐19 pandemic

et al. 2020

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“…Pathology analysis of COVID-19 patients' lungs shows widespread thrombosis with microangiopathy. It is yet to be determined whether plasmin in COVID-19 is a friend or foe as recently summarized in a review by Medcalf et al [ 94 ].…”

Section: Role Of Plasmin During the Cytokine Storm Or Cytokine Releasmentioning

confidence: 99%

The multifaceted role of plasminogen in inflammation

Heissig

Salama

Takahashi

et al. 2020

Cellular Signalling

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A fine-tuned activation and deactivation of proteases and their inhibitors are involved in the execution of the inflammatory response. The zymogen/proenzyme plasminogen is converted to the serine protease plasmin, a key fibrinolytic factor by plasminogen activators including tissue-type plasminogen activator (tPA). Plasmin is part of an intricate protease network controlling proteins of initial hemostasis/coagulation, fibrinolytic and complement system. Activation of these protease cascades is required to mount a proper inflammatory response. Although best known for its ability to dissolve clots and cleave fibrin, recent studies point to the importance of fibrin-independent functions of plasmin during acute inflammation and inflammation resolution. In this review, we provide an up-to-date overview of the current knowledge of the enzymatic and cytokine-like effects of tPA and describe the role of tPA and plasminogen receptors in the regulation of the inflammatory response with emphasis on the cytokine storm syndrome such as observed during coronavirus disease 2019 or macrophage activation syndrome. We discuss tPA as a modulator of Toll like receptor signaling, plasmin as an activator of NFkB signaling, and summarize recent studies on the role of plasminogen receptors as controllers of the macrophage conversion into the M2 type and as mediators of efferocytosis during inflammation resolution.

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“…Coagulopathy is another of the main complications of COVID-19-triggered cytokine storm, suggesting the potential role of anti-thrombotic agents to prevent venous thromboembolism. Coagulation is activated by the inflammatory response through several pro-coagulant pathways (Connors and Levy, 2020) and it presents with a considerable increase of D-dimer levels that could be ascribable to the attempt of the fibrinolytic system to remove fibrin and necrotic tissue from the lung parenchyma (Medcalf et al, 2020). Indeed, it has also been suggested that fibrinolytic therapy may be an effective pharmacological strategy to treat acute lung injury in COVID-19 patients (Liu et al, 2018).…”

Section: Drugs Potentially Counteracting the Effects Of Sars-cov-2 Inmentioning

confidence: 99%

Challenges for Drug Repurposing in the COVID-19 Pandemic Era

et al. 2020

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The coronavirus disease (COVID-19) pandemic has affected an estimated 16 million persons and caused 0.6 million deaths worldwide by September 2020. The pandemic has led to a rush to repurpose existing drugs, although the underlying evidence base is of variable quality. The improving knowledge of the virology and clinical presentation of COVID-19 is leading to a broadening pool of potential pharmacological targets. The aim of this review is to describe regulatory and pharmacological aspects of drug repurposing and to identify drugs proposed for repurposing in COVID-19 based on registered clinical trials, discussing the evidence to support their use in the treatment of this disease. The challenges of the correct interpretation of existing pre-clinical/clinical evidence as well as the generation of new evidence concerning drug repurposing in COVID-19 will also be discussed.

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Fibrinolysis and COVID‐19: A plasmin paradox

Cited by 89 publications

References 38 publications

Obesity: A critical risk factor in the COVID‐19 pandemic

Obesity: A critical risk factor in the COVID‐19 pandemic

The multifaceted role of plasminogen in inflammation

Challenges for Drug Repurposing in the COVID-19 Pandemic Era

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