Patients with coronavirus disease-19 (COVID-19) are at high risk for thrombotic arterial and venous occlusions. However, bleeding complications have also been observed in some patients. Understanding the balance between coagulation and fibrinolysis will help inform optimal approaches to thrombosis prophylaxis and potential utility of fibrinolytic-targeted therapies. 118 hospitalized COVID-19 patients and 30 healthy controls were included in the study. We measured plasma antigen levels of tissue-type plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) and performed spontaneous clot-lysis assays. We found markedly elevated tPA and PAI-1 levels in patients hospitalized with COVID-19. Both factors demonstrated strong correlations with neutrophil counts and markers of neutrophil activation. High levels of tPA and PAI-1 were associated with worse respiratory status. High levels of tPA, in particular, were strongly correlated with mortality and a significant enhancement in spontaneous ex vivo clot-lysis. While both tPA and PAI-1 are elevated among COVID-19 patients, extremely high levels of tPA enhance spontaneous fibrinolysis and are significantly associated with mortality in some patients. These data indicate that fibrinolytic homeostasis in COVID-19 is complex with a subset of patients expressing a balance of factors that may favor fibrinolysis. Further study of tPA as a biomarker is warranted.
【저자키워드】 viral infection, Biomarkers, thrombosis, Cardiovascular biology, 【초록키워드】 COVID-19, coronavirus disease, coronavirus, Biomarker, Mortality, thrombosis, neutrophil, fibrinolysis, Antigen, Coagulation, Prophylaxis, Coronavirus disease-19, Patient, bleeding, Complication, understanding, plasma, correlation, utility, patients, homeostasis, COVID-19 patients, Therapies, hospitalized COVID-19 patient, marker, neutrophil activation, high risk, balance, in some, respiratory status, Ex vivo, Factor, healthy control, These data, complex, fibrinolytic, help, neutrophil count, favor, thrombotic, neutrophil counts, while, Thrombosis prophylaxis, lysis, approach, venous, ENhance, performed, significantly, assays, elevated, demonstrated, correlated, expressing, subset, patients hospitalized, with COVID-19, 【제목키워드】 hospitalized COVID-19 patient, tissue plasminogen activator,