The Central Role of PAI-1 in COVID-19: Thrombosis and beyond

Fibrinolytic Proteins and Factor XIII as Predictors of Thrombotic and Hemorrhagic Complications in Hospitalized COVID-19 Patients

“…This assay represents the dynamic analysis of specific aspects of hemostasis, and particularly, in our study, compared to controls, patients displayed shorter CFT and higher MCF values. These signs of hypercoagulability by ROTEM testing are not novel, and our results are consistent with the findings of studies showing shorter CFT and higher MCF in COVID-19 patients (25,(41)(42)(43).…”

“…Interestingly, in our study, we could identify high baseline PAI-1 and t-PA levels as independent predictors of thrombosis during follow-up. This association further supports the central role of endothelial dysfunction and PAI-1 at the intersection of pulmonary and cardiovascular complications in COVID-19 infection (40,42), suggesting the targeted inhibition of PAI-1 as a novel therapeutic option to improve outcomes beyond thrombosis in these patients. Together with these two fibrinolytic biomarkers, we found that also a high NLR value at enrollment was independently associated with thrombosis at follow-up.…”

The favorable impacts of silibinin polyphenols as adjunctive therapy in reducing the complications of COVID-19: A review of research evidence and underlying mechanisms

“…In addition, they observed that silibinin considerably decreases the expression of TNF-α and inflammatory cytokines such as genes MCP-1, IL-6, and PAI-1 [28] . The latter is an indicator of endothelial dysfunction, which contributes to the thrombotic events of COVID-19 [115] . However, one of the limitations of such studies was the lack of clinical trials or very few human studies which are encouraged to investigate in detail the mechanism of action of this compound on molecular pathways.…”

Hypoxia and Hypercoagulability in COVID-19: Chicken or the Egg?

“…11 In COVID-19 patients, plasminogen activator inhibitor 1 is thought to play a central role in coagulation cascade initiation, inhibition of fibrinolysis, and overall morbidity in severe disease presentations. 12 Not surprisingly, Corey et al 4 demonstrated significant elevations of plasminogen activator inhibitor 1 in patients with severe COVID-19 ARDS and a significant association between elevated plasminogen activator inhibitor 1 concentrations, thromboembolic events, and mortality. Although their single-center cohort is relatively small and limited by a variety of prophylactic and therapeutic anticoagulation regimens received by study patients, these results are promising.…”