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

IntroductionIn a prospective cohort of hospitalized COVID-19 patients, an extensive characterization of hemostatic alterations by both global and specific assays was performed to clarify mechanisms underlying the coagulopathy and identify predictive factors for thrombotic and hemorrhagic events duri...

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Main Authors: Marina Marchetti, Patricia Gomez-Rosas, Laura Russo, Sara Gamba, Eleonora Sanga, Cristina Verzeroli, Chiara Ambaglio, Francesca Schieppati, Francesco Restuccia, Ezio Bonanomi, Marco Rizzi, Stefano Fagiuoli, Andrea D’Alessio, Grigorios T. Gerotziafas, Luca Lorini, Anna Falanga
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-06-01
Series:Frontiers in Cardiovascular Medicine
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fcvm.2022.896362/full
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author Marina Marchetti
Patricia Gomez-Rosas
Patricia Gomez-Rosas
Laura Russo
Sara Gamba
Eleonora Sanga
Cristina Verzeroli
Chiara Ambaglio
Francesca Schieppati
Francesco Restuccia
Ezio Bonanomi
Marco Rizzi
Stefano Fagiuoli
Andrea D’Alessio
Grigorios T. Gerotziafas
Luca Lorini
Anna Falanga
Anna Falanga
author_facet Marina Marchetti
Patricia Gomez-Rosas
Patricia Gomez-Rosas
Laura Russo
Sara Gamba
Eleonora Sanga
Cristina Verzeroli
Chiara Ambaglio
Francesca Schieppati
Francesco Restuccia
Ezio Bonanomi
Marco Rizzi
Stefano Fagiuoli
Andrea D’Alessio
Grigorios T. Gerotziafas
Luca Lorini
Anna Falanga
Anna Falanga
author_sort Marina Marchetti
collection DOAJ
description IntroductionIn a prospective cohort of hospitalized COVID-19 patients, an extensive characterization of hemostatic alterations by both global and specific assays was performed to clarify mechanisms underlying the coagulopathy and identify predictive factors for thrombotic and hemorrhagic events during hospitalization.Materials and MethodsIntensive care unit (ICU; n = 46) and non-ICU (n = 55) patients were enrolled, and the occurrence of thrombotic and hemorrhagic events was prospectively monitored. At study inclusion, thromboelastometry together with the measurement of specific coagulation proteins and hypercoagulation markers was performed.ResultsPatients (median age 67 years) showed significantly shorter clot formation time together with greater maximum clot firmness by thromboelastometry, increased levels of F1 + 2 and D-dimer, as biomarkers of hypercoagulability, and of procoagulant factors V, VIII, IX, XI, and fibrinogen, while FXIII was significantly reduced. The concentration of fibrinolytic proteins, tissue plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) were elevated in the overall cohort of patients. Many of these hemostatic alterations were significantly greater in ICU compared to non-ICU subjects and, furthermore, they were associated with inflammatory biomarker elevation [i.e., interleukin 6 (IL-6), C-reactive protein (CRP), neutrophil to lymphocyte ratio (NLR), and procalcitonin]. After enrollment, 7 thrombosis and 14 major bleedings occurred. Analysis of clinical and biological data identified increased t-PA, PAI-1, and NLR values as independent predictive factors for thrombosis, while lower FXIII levels were associated with bleeding.ConclusionThis study demonstrates alterations in all different hemostatic compartments analyzed, particularly in severe COVID-19 conditions, that strongly correlated with the inflammatory status. A potential role of fibrinolytic proteins together with NLR and of FXIII as predictors of thrombotic and hemorrhagic complications, respectively, is highlighted.
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spelling doaj.art-f66313e950aa46dbb5cc5f8adad744e22022-12-22T03:21:59ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2022-06-01910.3389/fcvm.2022.896362896362Fibrinolytic Proteins and Factor XIII as Predictors of Thrombotic and Hemorrhagic Complications in Hospitalized COVID-19 PatientsMarina Marchetti0Patricia Gomez-Rosas1Patricia Gomez-Rosas2Laura Russo3Sara Gamba4Eleonora Sanga5Cristina Verzeroli6Chiara Ambaglio7Francesca Schieppati8Francesco Restuccia9Ezio Bonanomi10Marco Rizzi11Stefano Fagiuoli12Andrea D’Alessio13Grigorios T. Gerotziafas14Luca Lorini15Anna Falanga16Anna Falanga17Department of Immunohematology and Transfusion Medicine, Hospital Papa Giovanni XXIII, Bergamo, ItalyDepartment of Immunohematology and Transfusion Medicine, Hospital Papa Giovanni XXIII, Bergamo, ItalyHematology Service, Hospital General Regional Tecamac Instituto Mexicano del Seguro Social (IMSS), Mexico, MexicoDepartment of Immunohematology and Transfusion Medicine, Hospital Papa Giovanni XXIII, Bergamo, ItalyDepartment of Immunohematology and Transfusion Medicine, Hospital Papa Giovanni XXIII, Bergamo, ItalyDepartment of Immunohematology and Transfusion Medicine, Hospital Papa Giovanni XXIII, Bergamo, ItalyDepartment of Immunohematology and Transfusion Medicine, Hospital Papa Giovanni XXIII, Bergamo, ItalyDepartment of Immunohematology and Transfusion Medicine, Hospital Papa Giovanni XXIII, Bergamo, ItalyDepartment of Immunohematology and Transfusion Medicine, Hospital Papa Giovanni XXIII, Bergamo, ItalyDepartment of Anesthesiology and Critical Care Medicine, Hospital Papa Giovanni XXIII, Bergamo, ItalyDepartment of Anesthesiology and Critical Care Medicine, Hospital Papa Giovanni XXIII, Bergamo, ItalyUnit of Infectious Diseases, Hospital Papa Giovanni XXIII, Bergamo, ItalyDepartment of Internal Medicine, Hospital Papa Giovanni XXIII, Bergamo, ItalyMedical Oncology and Internal Medicine, Policlinico San Marco – Gruppo San Donato, Bergamo, ItalySorbonne Université, INSERM UMR_S938, Research Group “Cancer-Hemostasis-Angiogenesis”, Centre de Recherche Saint-Antoine, Institut Universitaire de Cancérologie, Paris, FranceDepartment of Anesthesiology and Critical Care Medicine, Hospital Papa Giovanni XXIII, Bergamo, ItalyDepartment of Immunohematology and Transfusion Medicine, Hospital Papa Giovanni XXIII, Bergamo, ItalySchool of Medicine and Surgery, University of Milano Bicocca, Milan, ItalyIntroductionIn a prospective cohort of hospitalized COVID-19 patients, an extensive characterization of hemostatic alterations by both global and specific assays was performed to clarify mechanisms underlying the coagulopathy and identify predictive factors for thrombotic and hemorrhagic events during hospitalization.Materials and MethodsIntensive care unit (ICU; n = 46) and non-ICU (n = 55) patients were enrolled, and the occurrence of thrombotic and hemorrhagic events was prospectively monitored. At study inclusion, thromboelastometry together with the measurement of specific coagulation proteins and hypercoagulation markers was performed.ResultsPatients (median age 67 years) showed significantly shorter clot formation time together with greater maximum clot firmness by thromboelastometry, increased levels of F1 + 2 and D-dimer, as biomarkers of hypercoagulability, and of procoagulant factors V, VIII, IX, XI, and fibrinogen, while FXIII was significantly reduced. The concentration of fibrinolytic proteins, tissue plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) were elevated in the overall cohort of patients. Many of these hemostatic alterations were significantly greater in ICU compared to non-ICU subjects and, furthermore, they were associated with inflammatory biomarker elevation [i.e., interleukin 6 (IL-6), C-reactive protein (CRP), neutrophil to lymphocyte ratio (NLR), and procalcitonin]. After enrollment, 7 thrombosis and 14 major bleedings occurred. Analysis of clinical and biological data identified increased t-PA, PAI-1, and NLR values as independent predictive factors for thrombosis, while lower FXIII levels were associated with bleeding.ConclusionThis study demonstrates alterations in all different hemostatic compartments analyzed, particularly in severe COVID-19 conditions, that strongly correlated with the inflammatory status. A potential role of fibrinolytic proteins together with NLR and of FXIII as predictors of thrombotic and hemorrhagic complications, respectively, is highlighted.https://www.frontiersin.org/articles/10.3389/fcvm.2022.896362/fullCOVID-19thrombosisbleedinghypercoagulabilitythromboelastometryfibrinolysis
spellingShingle Marina Marchetti
Patricia Gomez-Rosas
Patricia Gomez-Rosas
Laura Russo
Sara Gamba
Eleonora Sanga
Cristina Verzeroli
Chiara Ambaglio
Francesca Schieppati
Francesco Restuccia
Ezio Bonanomi
Marco Rizzi
Stefano Fagiuoli
Andrea D’Alessio
Grigorios T. Gerotziafas
Luca Lorini
Anna Falanga
Anna Falanga
Fibrinolytic Proteins and Factor XIII as Predictors of Thrombotic and Hemorrhagic Complications in Hospitalized COVID-19 Patients
Frontiers in Cardiovascular Medicine
COVID-19
thrombosis
bleeding
hypercoagulability
thromboelastometry
fibrinolysis
title Fibrinolytic Proteins and Factor XIII as Predictors of Thrombotic and Hemorrhagic Complications in Hospitalized COVID-19 Patients
title_full Fibrinolytic Proteins and Factor XIII as Predictors of Thrombotic and Hemorrhagic Complications in Hospitalized COVID-19 Patients
title_fullStr Fibrinolytic Proteins and Factor XIII as Predictors of Thrombotic and Hemorrhagic Complications in Hospitalized COVID-19 Patients
title_full_unstemmed Fibrinolytic Proteins and Factor XIII as Predictors of Thrombotic and Hemorrhagic Complications in Hospitalized COVID-19 Patients
title_short Fibrinolytic Proteins and Factor XIII as Predictors of Thrombotic and Hemorrhagic Complications in Hospitalized COVID-19 Patients
title_sort fibrinolytic proteins and factor xiii as predictors of thrombotic and hemorrhagic complications in hospitalized covid 19 patients
topic COVID-19
thrombosis
bleeding
hypercoagulability
thromboelastometry
fibrinolysis
url https://www.frontiersin.org/articles/10.3389/fcvm.2022.896362/full
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