scholarly journals The role of Plasminogen Activator Inhibitor 1 in predicting sepsis-associated liver dysfunction: an observational study

2020 ◽  
Author(s):  
Ewa Woznica Niesobska ◽  
Patrycja Lesnik ◽  
Ryszard Woznica ◽  
Jaroslaw Janc ◽  
Malgorzata Zalewska ◽  
...  
Keyword(s):  
Septic Shock ◽  
Observational Study ◽  
Plasminogen Activator ◽  
Liver Dysfunction ◽  
Plasminogen Activator Inhibitor ◽  
Rank Test ◽  
Plasminogen Activator Inhibitor 1 ◽  
Log Rank Test ◽  
Activator Inhibitor ◽  
Pai 1

Abstract Background Sepsis-associated liver dysfunction (SALD) is associated with poor prognosis and an increased mortality in Intensive Care Unit (ICU). Bilirubin is one of the components of Sequential Organ Failure Assessment (SOFA) used in Sepsis−3 criteria. Hyperbilirubinemia is a late and non specific symptom of liver dysfunction. The aim of the study was to identify plasma biomarkers, which could be used for an early diagnosis of SALD. Methods A single-centre, prospective observational study was conducted in the ICU of Wroclaw University Hospital. Plasma biomarkers - prothrombin time, INR, antithrombin III, bilirubin, aspartate transaminase (AST), alanine transaminase, albumin, endothelin-1, hepcidin, plasminogen activator inhibitor-1 (PAI-1), thrombin-antithrombin complex and interferon-gamma inducible protein 10 kDa were analysed. Plasma samples were obtained from eligible septic patients within 24 hours after having developed sepsis/septic shock. Enrolled patients were followed for 14 days for developing SALD and 28 days for overall survival. Results Seventy-nine patients were enrolled into the study, and 24 (30,4%) of them developed SALD. PAI-1 with cut-off value of 9 ng/ml was shown to be a good predictor of SALD (AUC = 0,727, sensitivity 79,2%; specificity 41,8%; accuracy 53,2%) and of 28-day survival in patients with sepsis/septic shock (log rank test, p = 0,00091). In combination with AST it was also useful in predicting 28-day survival (log rank test, p = 0,00242). Conclusions Sepsis-associated hyperbilirubinemia is frequent, but bilirubin is a late and non specific marker of SALD. Measuring PAI-1 serum levels at the onset of sepsis/ septic shock may be useful in predicting the development of SALD. A combination of PAI-1 and AST predicts better the 28-day survival, than PAI-1 alone, but due to low cut-off values of AST it might not be clinically significant.

scholarly journals The role of Plasminogen Activator Inhibitor 1 in predicting sepsis-associated liver dysfunction: an observational study

2021 ◽  
Author(s):  
Ewa Woznica Niesobska ◽  
Patrycja Lesnik ◽  
Ryszard Woznica ◽  
Jaroslaw Janc ◽  
Malgorzata Zalewska ◽  
...  
Keyword(s):  
Septic Shock ◽  
Observational Study ◽  
Plasminogen Activator ◽  
Liver Dysfunction ◽  
Plasminogen Activator Inhibitor ◽  
Rank Test ◽  
Plasminogen Activator Inhibitor 1 ◽  
Log Rank Test ◽  
Activator Inhibitor ◽  
Pai 1

Abstract Background: Sepsis-associated liver dysfunction (SALD) is associated with poor prognosis and increased mortality in the Intensive Care Unit. Bilirubin is one of the components of Sequential Organ Failure Assessment used in Sepsis-3 criteria. Hyperbilirubinemia is a late and non-specific symptom of liver dysfunction. The aim of the study was to identify plasma biomarkers, which could be used for the early diagnosis of SALD.Methods: A single-centre, prospective observational study was conducted in the ICU of Wroclaw University Hospital. Plasma biomarkers - prothrombin time, INR, antithrombin III, bilirubin, aspartate transaminase (AST), alanine transaminase, alkaline phosphatase, gamma glutamyl transferase, albumin, endothelin-1, hepcidin, plasminogen activator inhibitor-1 (PAI-1), thrombin-antithrombin complex and interferon-gamma inducible protein 10 kDa were analysed. Plasma samples were obtained from eligible septic patients within 24 hours after having developed sepsis/septic shock. Enrolled patients were followed for 14 days for developing SALD and 28 days for overall survival.Results: 79 patients were enrolled in the study, and 24 (30.4%) of them developed SALD. PAI-1 with a cut-off value of 9ng/ml was shown to be a predictor of SALD (AUC=0.727, sensitivity 79.2%; specificity 41.8%; accuracy 53.2%) and of 28-day survival in patients with sepsis/septic shock (log rank test, p=0.00091). This was also useful in predicting 28-day survival, in combination with AST (log rank test, p=0.00242).Conclusions: Sepsis-associated hyperbilirubinemia is frequent, but bilirubin is a late and non-specific marker of SALD. Measuring PAI-1 serum levels at the onset of sepsis/ septic shock may be useful in predicting the development of SALD. A combination of PAI-1 and AST better predicts the 28-day survival than PAI-1 alone, but due to the low cut-off values of AST, this might not be clinically significant.

Plasminogen Activator Inhibitor 1: A New Prognostic Marker in Septic Shock

1989 ◽  
Vol 61 (03) ◽  
pp. 459-462 ◽  
Author(s):  
Gerard Pralong ◽  
Thierry Calandra ◽  
Michel-P Glausef ◽  
Joop Schellekens ◽  
Jan Verhoef ◽  
...  
Keyword(s):  
Septic Shock ◽  
Plasminogen Activator ◽  
Prognostic Significance ◽  
Elevated Serum ◽  
Plasminogen Activator Inhibitor ◽  
Threshold Level ◽  
Control Group ◽  
Plasminogen Activator Inhibitor 1 ◽  
Activator Inhibitor ◽  
Pai 1

SummaryThe prognostic value of plasminogen activator inhibitor type 1 (PAI-1) in septic shock was investigated in 52 patients with septic shock. The patients had significantly elevated serum PAI-1 levels with respect to the control group (p = 0.002). In patients not having a rapidly fatal underlying disease, PAI-1 was significantly higher in patients dying within a week after onset of shock than in survivors (median PAI-1: 900 and 307 ng/ml, respectively; p = 0.001). The analysis of the distribution of PAI-1 levels permitted retrospectively to determine a threshold level of PAI-1 which had prognostic significance. Mortality was 71% in patients with serum PAI-1 above 550 ng/ml, whereas only two patients (6%) having a PAI-1 below 550 ng/ml died within a week.Thus, in patients with septic shock, PAI-1 appears to have a strong predictive value as to mortality. This early marker may help the clinician in identifying a subgroup of patients particularly at risk.

943: Plasminogen Activator Inhibitor 1 (PAI-1) is Increased in Human Peyronie's Disease

2005 ◽  
Vol 173 (4S) ◽  
pp. 255-255 ◽  
Author(s):  
Hugo H. Davila ◽  
Thomas R. Magee ◽  
Freddy Zuniga ◽  
Jacob Rajfer ◽  
Nestor F. GonzalezCadavid
Keyword(s):  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Peyronie’S Disease ◽  
Plasminogen Activator Inhibitor 1 ◽  
Peyronie's Disease ◽  
Activator Inhibitor ◽  
Pai 1

Relationship of Plasminogen Activator Inhibitor-1 Levels following Thrombolytic Therapy with rt-PA as Compared to Streptokinase and Patency of Infarct Related Coronary Artery

1999 ◽  
Vol 82 (07) ◽  
pp. 104-108 ◽  
Author(s):  
Franck Paganelli ◽  
Marie Christine Alessi ◽  
Pierre Morange ◽  
Jean Michel Maixent ◽  
Samuel Lévy ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Thrombolytic Therapy ◽  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Control Group ◽  
Plasminogen Activator Inhibitor 1 ◽  
Vessel Patency ◽  
Activator Inhibitor ◽  
Pai 1

Summary Background: Type 1 plasminogen activator inhibitor (PAI-1) is considered to be risk factor for acute myocardial infarction (AMI). A rebound of circulating PAI-1 has been reported after rt-PA administration. We investigated the relationships between PAI-1 levels before and after thrombolytic therapy with streptokinase (SK) as compared to rt-PA and the patency of infarct-related arteries. Methods and Results: Fifty five consecutive patients with acute MI were randomized to strep-tokinase or rt-PA. The plasma PAI-1 levels were studied before and serially within 24 h after thrombolytic administration. Vessel patency was assessed by an angiogram at 5 ± 1days. The PAI-1 levels increased significantly with both rt-PA and SK as shown by the levels obtained from a control group of 10 patients treated with coronary angioplasty alone. However, the area under the PAI-1 curve was significantly higher with SK than with rt-PA (p <0.01) and the plasma PAI-1 levels peaked later with SK than with rt-PA (18 h versus 3 h respectively). Conversely to PAI-1 levels on admission, the PAI-1 levels after thrombolysis were related to vessel patency. Plasma PAI-1 levels 6 and 18 h after SK therapy and the area under the PAI-1 curve were significantly higher in patients with occluded arteries (p <0.002, p <0.04 and p <0.05 respectively).The same tendency was observed in the t-PA group without reaching significance. Conclusions: This study showed that the PAI-1 level increase is more pronounced after SK treatment than after t-PA treatment. There is a relationship between increased PAI-1 levels after thrombolytic therapy and poor patency. Therapeutic approaches aimed at quenching PAI-1 activity after thrombolysis might be of interest to improve the efficacy of thrombolytic therapy for acute myocardial infarction.

Fibrinolysis in Normal Subjects - Comparison Between Plasminogen Activator Inhibitor and Other Components of the Fibrinolytic System

1988 ◽  
Vol 59 (02) ◽  
pp. 299-303 ◽  
Author(s):  
Grazia Nicoloso ◽  
Jacques Hauert ◽  
Egbert K O Kruithof ◽  
Guy Van Melle ◽  
Fedor Bachmann
Keyword(s):  
Plasminogen Activator ◽  
Fibrinolytic Activity ◽  
Plasminogen Activator Inhibitor ◽  
Venous Occlusion ◽  
Venous Stasis ◽  
Plasminogen Activator Inhibitor 1 ◽  
Plate Assay ◽  
Fibrin Plate ◽  
Activator Inhibitor ◽  
Pai 1

SummaryWe analyzed fibrinolytic parameters in 20 healthy men and 20 healthy women, aged from 25 to 59, before and after 10 and 20 min venous occlusion. The 10 min post-occlusion fibrinolytic activity measured directly in diluted unfractionated plasma by a highly sensitive 125I-fibrin plate assay correlated well with the activity of euglobulins determined by the classical fibrin plate assay (r = 0.729), but pre-stasis activities determined with these two methods did not correlate (r = 0.084). The enhancement of fibrinolytic activity after venous occlusion was mainly due to an increase of t-PA in the occluded vessels (4-fold increase t-PA antigen after 10 min and 8-fold after 20 min venous occlusion). Plasminogen activator inhibitor (PAI) activity and plasminogen activator inhibitor 1 (PAI-1)1 antigen levels at rest showed considerable dispersion ranging from 1.9 to 12.4 U/ml, respectively 6.9 to 77 ng/ml. A significant increase of PAI-1 antigen levels was observed after 10 and 20 min venous occlusion. At rest no correlation was found between PAI activity or PAI-1 antigen levels and the fibrinolytic activity measured by 125I-FPA. However, a high level of PAI-1 at rest was associated with a high prestasis antigen level of t-PA and a low fibrinolytic response after 10 min of venous stasis. Since the fibrinolytic response inversely correlated with PAI activity at rest, we conclude that its degree depends mainly on the presence of free PAI.

A Specific Immunologic Assay for Functional Plasminogen Activator Inhibitor 1 in Plasma – Standardized Measurements of the Inhibitor and Related Parameters in Patients with Venous Thromboembolic Disease

1992 ◽  
Vol 68 (05) ◽  
pp. 486-494 ◽  
Author(s):  
Malou Philips ◽  
Anne-Grethe Juul ◽  
Johan Selmer ◽  
Bent Lind ◽  
Sixtus Thorsen
Keyword(s):  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Normal Subjects ◽  
Tissue Type ◽  
Blood Collection ◽  
Plasminogen Activator Inhibitor 1 ◽  
Type Plasminogen Activator ◽  
Significant Difference ◽  
Activator Inhibitor ◽  
Pai 1

SummaryA new assay for functional plasminogen activator inhibitor 1 (PAI-1) in plasma was developed. The assay is based on the quantitative conversion of PAI-1 to urokinase-type plasminogen activator (u-PA)-PAI-l complex the concentration of which is then determined by an ELISA employing monoclonal anti-PAI-1 as catching antibody and monoclonal anti-u-PA as detecting antibody. The assay exhibits high sensitivity, specificity, accuracy, and precision. The level of functional PAI-1, tissue-type plasminogen activator (t-PA) activity and t-PA-PAI-1 complex was measured in normal subjects and in patients with venous thromboembolism in a silent phase. Blood collection procedures and calibration of the respective assays were rigorously standardized. It was found that the patients had a decreased fibrinolytic capacity. This could be ascribed to high plasma levels of PAI-1. The release of t-PA during venous occlusion of an arm for 10 min expressed as the increase in t-PA + t-PA-PAI-1 complex exhibited great variation and no significant difference could be demonstrated between the patients with a thrombotic tendency and the normal subjects.

Relation between Plasminogen Activator Inhibitor-1 and Hepatic Enzyme Concentrations in Hyperlipidemic Patients

1994 ◽  
Vol 72 (03) ◽  
pp. 434-437 ◽  
Author(s):  
E Bruckert ◽  
A Ankri ◽  
P Glral ◽  
G Turpin
Keyword(s):  
Blood Pressure ◽  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Tolerance Test ◽  
High Plasma ◽  
Oral Glucose ◽  
Plasminogen Activator Inhibitor 1 ◽  
Glutamyl Transferase ◽  
Activator Inhibitor ◽  
Pai 1

SummaryPlasminogen activator inhibitor type-1 (PAI-1) is a key determinant of the fibrinolytic capacity. Its activity correlates with most of the characteristic features of insulin resistance syndrome, i. e. obesity, high blood pressure and hyperlipidemia.We measured plasma PAI-1 antigen levels in 131 asymptomatic men (aged 44.2 ± 11 years) who had been referred for hyperlipidemia. Those taking medication and those with a secondary hyperlipidemia were excluded.We confirmed the correlation between PAI-1 levels and the following variables: body mass index, blood pressure, triglyceride concentration, and blood glucose and insulin levels before and after an oral glucose tolerance test. We also found a significant and independent correlation between PAI-1 and the concentration of the hepatic enzymes glutamyl transferase, alanine aminotransferase and aspartate aminotransferase.Mild liver abnormalities (presumably steatosis) may thus be one of the factors accounting for high plasma PAI-1 levels in hyperlipidemic patients.

The Roles of α2-Antiplasmin and Plasminogen Activator Inhibitor 1 (PAI-1) in the Inhibition of Clot Lysis

1993 ◽  
Vol 70 (02) ◽  
pp. 301-306 ◽  
Author(s):  
Linda A Robbie ◽  
Nuala A Booth ◽  
Alison M Croll ◽  
Bruce Bennett
Keyword(s):  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Fibrin Clot ◽  
Clot Lysis ◽  
Plasminogen Activator Inhibitor 1 ◽  
Dependent Inhibition ◽  
Activator Inhibitor ◽  
Pai 1

SummaryThe relative importance of the two major inhibitors of fibrinolysis, α2-antiplasmin (α2-AP) and plasminogen activator inhibitor (PAI-1), were investigated using a simple microtitre plate system to study fibrin clot lysis in vitro. Cross-linked fibrin clots contained plasminogen and tissue plasminogen activator (t-PA) at concentrations close to physiological. Purified α2-AP and PAI-1 caused dose-dependent inhibition. All the inhibition due to normal plasma, either platelet-rich or poor, was neutralised only by antibodies to α2-AP. Isolated platelets, at a final concentration similar to that in blood, 2.5 × 108/ml, markedly inhibited clot lysis. This inhibition was neutralised only by antibodies to PAI-1. At the normal circulating ratio of plasma to platelets, α2-AP was the dominant inhibitor. When the platelet:plasma ratio was raised some 20-fold, platelet PAI-1 provided a significant contribution. High local concentrations of PAI-1 do occur in thrombi in vivo, indicating a role for PAI-1, complementary to that of α2-AP, in such situations.

Determinants of Plasminogen Activator Inhibitor-1 Activity in Survivors of Myocardial Infarction

1995 ◽  
Vol 73 (02) ◽  
pp. 261-267 ◽  
Author(s):  
Rosaire P Gray ◽  
Vidya Mohamed-Ali ◽  
David L H Patterson ◽  
John S Yudkin
Keyword(s):  
Myocardial Infarction ◽  
Plasminogen Activator ◽  
Plasma Insulin ◽  
Plasminogen Activator Inhibitor ◽  
Immunoreactive Insulin ◽  
Plasminogen Activator Inhibitor 1 ◽  
Serum Triglycerides ◽  
Fasting Plasma ◽  
Activator Inhibitor ◽  
Pai 1

SummaryA significant relationship has been described between plasminogen activator inhibitor-1 (PAI-1) and plasma insulin concentrations. However, most radioimmunoassays (RIA) substantially overestimate plasma insulin concentrations because of cross reaction with proinsulin-like molecules and it has been proposed that proinsulin-like molecules may be important determinants of PAI-1 activity. We measured fasting plasma immunoreactive insulin by conventional RIA, fasting plasma insulin (EIMA) by specific two site immuno-enzymometric assay, and intact proinsulin and des-31,32-proinsulin by two site immunoradiometric assay (IRMA) in 74 (50 nondiabetic and 24 diabetic) subjects who had survived a myocardial infarction between 6 and 24 months previously. In univariate analysis, PAI-1 activity correlated with serum triglycerides (rs=0.43; p <0.0001), insulin sensitivity (rs = -0.30; p = 0.004), and immunoreactive insulin (rs = 0.45; p <0.0001). However, the relationship between PAI-1 activity and plasma specific insulin (IEMA) was weaker (rs = 0.24; p = 0.019) than those with intact proinsulin (rs = 0.53; p <0.0001) and des-31,32-proinsulin (rs = 0.54; p <0.0001) despite the low concentrations of these proinsulin-like molecules. In multiple regression analysis, only des-31,32-proinsulin (p = 0.001) and serum triglycerides (p = 0.013) were significant determinants of PAI-1 activity. In conclusion, these results suggest that proinsulin-like molecules and serum triglycerides are important determinants of PAI-1 activity in survivors of myocardial infarction.

Localization of a Vitronectin Binding Region of Plasminogen Activator Inhibitor-1

1995 ◽  
Vol 73 (05) ◽  
pp. 829-834 ◽  
Author(s):  
Jaya Padmanabhan ◽  
David C Sane
Keyword(s):  
Binding Site ◽  
Plasminogen Activator ◽  
Inhibitory Activity ◽  
Plasminogen Activator Inhibitor ◽  
Structural Homology ◽  
Binding Region ◽  
Plasminogen Activator Inhibitor 1 ◽  
Activator Inhibitor ◽  
Pai 1

SummaryThe PAI-1 binding site for VN was studied using two independent methods. PAI-1 was cleaved by Staph V8 protease, producing 8 fragments, only 2 of which bound to [125I]-VN. These fragments were predicted to overlap between residues 91-130. Since PAI-2 has structural homology to PAI-1, but does not bind to vitronectin, chimeras of PAI-1 and PAI-2 were constructed. Four chimeras, containing PAI-1 residues 1-70,1-105,1-114, and 1-167 were constructed and expressed in vitro. PAI-1, PAI-2, and all of the chimeras retained inhibitory activity for t-PA, but only the chimera containing PAI-1 residues 1-167 formed a complex with VN. Together, these results predict that the VN binding site of PAI-1 is between residues 115-130.

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