Assessment of Fibrinolysis in Sepsis Patients with Urokinase Modified Thromboelastography

• Published in: PloS one Vol. 10; no. 8; p. e0136463
• Main Authors: Panigada, Mauro, Zacchetti, Lucia, L'Acqua, Camilla, Cressoni, Massimo, Anzoletti, Massimo Boscolo, Bader, Rossella, Protti, Alessandro, Consonni, Dario, D'Angelo, Armando, Gattinoni, Luciano
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 26.08.2015; Public Library of Science (PLoS)
• Subjects: Activated clay; Adult; Aged; Anesthesiology; Bilirubin; Biomarkers - analysis; Case-Control Studies; Complications and side effects; Confidence intervals; Consent; Damage detection; Discharge; Female; Fibrinolysis; Hemophilia; Humans; Impairment; Infections; Inhibitors; Intensive care; Intensive Care Units; Kaolin; Lactic acid; Male; Markers; Middle Aged; Morbidity; Mortality; Patients; Physiological aspects; Pilot Projects; Plasminogen activator inhibitors; Point-of-Care Systems; Prospective Studies; Sepsis; Sepsis - physiopathology; Septic shock; Statistical analysis; Thrombelastography - methods; Thrombin; Thrombosis; U-Plasminogen activator; Urokinase; Viscoelasticity; Italy
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0136463

Impairment of fibrinolysis during sepsis is associated with worse outcome. Early identification of this condition could be of interest. The aim of this study was to evaluate whether a modified point-of-care viscoelastic hemostatic assay can detect sepsis-induced impairment of fibrinolysis and to correlate impaired fibrinolysis with morbidity and mortality. This single center observational prospective pilot study was performed in an adult Intensive Care Unit (ICU) of a tertiary academic hospital. Forty consecutive patients admitted to the ICU with severe sepsis or septic shock were included. Forty healthy individuals served as controls. We modified conventional kaolin activated thromboelastography (TEG) adding urokinase to improve assessment of fibrinolysis in real time (UK-TEG). TEG, UK-TEG, plasminogen activator inhibitor (PAI)-1, thrombin-activatable fibrinolysis inhibitor (TAFI), d-dimer, DIC scores and morbidity (rated with the SOFA score) were measured upon ICU admission. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs) of mortality at ICU discharge. UK-TEG revealed a greater impairment of fibrinolysis in sepsis patients compared to healthy individuals confirmed by PAI-1. TAFI was not different between sepsis patients and healthy individuals. 18/40 sepsis patients had fibrinolysis impaired according to UK-TEG and showed higher SOFA score (8 (6-13) vs 5 (4-7), p = 0.03), higher mortality (39% vs 5%, p = 0.01) and greater markers of cellular damage (lactate levels, LDH and bilirubin). Mortality at ICU discharge was predicted by the degree of fibrinolysis impairment measured by UK-TEG Ly30 (%) parameter (OR 0.95, 95% CI 0.93-0.98, p = 0.003). Sepsis-induced impairment of fibrinolysis detected at UK-TEG was associated with increased markers of cellular damage, morbidity and mortality.