Plasma tissue plasminogen activator and plasminogen activator inhibitor-1 in hospitalized COVID-19 patients
| العنوان: | Plasma tissue plasminogen activator and plasminogen activator inhibitor-1 in hospitalized COVID-19 patients |
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| المؤلفون: | Yu Zuo, Srilakshmi Yalavarthi, Alyssa Harbaugh, Mark Warnock, Yogendra Kanthi, Daniel A. Lawrence, Kelsey Gockman, Jason S. Knight, Jacqueline A. Madison, Melanie Zuo |
| المصدر: | Scientific Reports medRxiv Scientific Reports, Vol 11, Iss 1, Pp 1-9 (2021) |
| بيانات النشر: | Springer Science and Business Media LLC, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, Male, Neutrophils, medicine.medical_treatment, 030204 cardiovascular system & hematology, Tissue plasminogen activator, Gastroenterology, Severity of Illness Index, chemistry.chemical_compound, Leukocyte Count, 0302 clinical medicine, Aged, 80 and over, Multidisciplinary, Fibrinolysis, Middle Aged, Thrombosis, Hospitalization, Coagulation, Plasminogen activator inhibitor-1, Tissue Plasminogen Activator, Medicine, Biomarker (medicine), Female, medicine.drug, Adult, medicine.medical_specialty, Science, Article, Fibrin Fibrinogen Degradation Products, 03 medical and health sciences, Internal medicine, Plasminogen Activator Inhibitor 1, medicine, Humans, Aged, business.industry, SARS-CoV-2, Case-control study, COVID-19, medicine.disease, Cardiovascular biology, 030104 developmental biology, chemistry, Viral infection, Case-Control Studies, business, Plasminogen activator, Leukocyte L1 Antigen Complex, Ex vivo, Biomarkers |
| الوصف: | BackgroundPatients with coronavirus disease 19 (COVID-19) are at high risk for thrombotic arterial and venous occlusions. At the same time, bleeding complications have been observed in some patients. Better understanding the balance between coagulation and fibrinolysis will help inform optimal approaches to thrombosis prophylaxis and potential utility of fibrinolytic-targeted therapies.Methods118 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.FindingsWe found markedly elevated levels of tPA and PAI-1 among patients hospitalized with COVID-19. Both factors demonstrated a strong correlation 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 also strongly correlated with mortality and with a significant enhancement in spontaneous ex vivo clot lysis.InterpretationWhile 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, and suggest that further study of tPA as a potential biomarker is warranted.FundingCOVID-19 Cardiovascular Impact Research Ignitor Grant from the Michigan Medicine Frankel Cardiovascular Center, the National Institutes of Health, the A. Alfred Taubman Medical Research Institute, the Rheumatology Research Foundation, the Lupus Research Alliance, the Falk Medical Research Trust, the Burroughs Wellcome Fund, and the JOBST-American Venous Forum. |
| اللغة: | English |
| تدمد: | 2045-2322 |
| DOI: | 10.1038/s41598-020-80010-z |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::dc9753e79720d1b6e5b5a5a3112f1680Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....dc9753e79720d1b6e5b5a5a3112f1680 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20452322 |
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| DOI: | 10.1038/s41598-020-80010-z |