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.

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.

scholarly journals THE FIBRINOLYTIC ALTERATION ASSOCIATED WITH DAILY ADMINISTRATION OF SILDENAFIL

2018 ◽  
Vol 11 (8) ◽  
pp. 107
Author(s):  
Fathelrahman M Hassan
Keyword(s):  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Daily Administration ◽  
Control Group ◽  
Average Weight ◽  
Plasminogen Activator Inhibitor 1 ◽  
Control Groups ◽  
Activator Inhibitor ◽  
Pai 1 ◽  
D Dimer

Objective: The objective of this study was to determine the fibrinolytic alteration associated with daily administration of sildenafil.Methods: A total of 12 adult male rabbits without mortality rate had been fed standard and subdivided into four groups; their average weight was 1.5, 2.5, 1.9, and 2 kg randomly selected during the period of March 2012–July 2013. Depending on weight, the control groups (2.25 mg/1.5 kg day) and sildenafil groups (3 mg/2 kg/day, 2.85 mg/1.9 kg/day, and 1.7 mg/2.5 kg/day) were injected by normal saline and sildenafil concentration, respectively to create four groups, every group was composed of three rabbits; saline rabbit (control group, n=3) and sildenafil rabbits (sildenafil group, n=9). All rabbit’s plasma samples have been investigated for prothrombin time, activated partial thromboplastin time, fibrinogen, plasminogen activator inhibitor-1 (PAI-1), prothrombin fragment 1+2, tissues plasminogen activator (tPA), plasmin antiplasmin (PAP), plasminogen, and D-dimer after 24 h of administration.Results: The PAP level was significantly (p<0.05) decreased following sildenafil injection. Sildenafil-injected (3 mg/ml) rabbits had decreased the means of PAI-1 and mean tPA, as early as 1-day post-injection, with a considerable lower PAP first determined 3 days after injection that continued into each rabbit 2 and 3.Conclusion: Better strategies are to initiate and manipulate this drug ought to reduce the chance of each thrombosis and hemorrhage, at the same time as minimizing the need for laboratory monitoring with the aid of the use of PAI-1, tPA, and PAP checks.

The association between the 4G/5G polymorphism in the promoter of the plasminogen activator inhibitor-1 gene and deep venous thrombosis in young people

2005 ◽  
Vol 20 (1) ◽  
pp. 48-52 ◽  
Author(s):  
A Mansilha ◽  
F Araújo ◽  
M Severo ◽  
S M Sampaio ◽  
T Toledo ◽  
...  
Keyword(s):  
Young People ◽  
Venous Thrombosis ◽  
Deep Venous Thrombosis ◽  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Control Group ◽  
Plasminogen Activator Inhibitor 1 ◽  
Increased Risk ◽  
Activator Inhibitor ◽  
Pai 1

Objective: To evaluate the association between the 4G/5G polymorphism in the promoter of the plasminogen activator inhibitor-1 (PAI-1) gene and deep venous thrombosis (DVT) in young people. Methods: Prevalence of the 4G/5G polymorphism was investigated using DNA analysis in a population of 81 consecutive and unrelated patients with an objectively documented first episode of DVT under 40 years old and in a control group of 88 healthy subjects. Results: The frequency of genotypes among patients was 0.27 4G/4G, 0.49 4G/5G and 0.23 5G/5G, corresponding to a frequency of 0.52 for the 4G allele. In the control group the results were, respectively, 0.24, 0.44 and 0.32, corresponding to a frequency of 0.46 for the 4G allele. The odds ratio (OR) for homozygous 4G genotype was 1.5 (95% confidence interval: 0.7–3.6), which was not statistically significant ( P = 0.51). Conclusion: In this study, the 4G/5G polymorphism in the promoter of the PAI-1 gene, including the homozygous 4G genotype, was not associated with a significantly increased risk of DVT in young people.

scholarly journals Coagulopathy is Initiated with Endothelial Dysfunction and Disrupted Fibrinolysis in Patients with COVID-19

2021 ◽  
Author(s):  
FATMA BURCU BELEN APAK ◽  
Gulbahar Yuce ◽  
Deniz Ilhan Topcu ◽  
Ayse Gultekingil ◽  
Yunus Emre Felek ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Protein C ◽  
Plasminogen Activator Inhibitor ◽  
Control Group ◽  
Endothelial Protein C Receptor ◽  
Plasminogen Activator Inhibitor 1 ◽  
Tissue Plasminogen ◽  
Activator Inhibitor ◽  
Pai 1

Abstract Background: A substantial group of patients suffer coagulopathy of Covid-19 (CAC) and are presented with thrombosis. The pathogenesis involved in CAC is not fully understood.Objectives: We evaluated the hemostatic and inflammatory parameters of 51 hospitalized Covid-19 adult patients and 21 controls. The parameters analyzed were danger signal molecule (High molecular weight group box protein-1/HMGBP-1), platelet count, prothrombin time (PT), activated partial thromboplastin time (aPTT), D-dimer, fibrinogen, endothelial protein C receptor (EPCR), soluble E-selectin, soluble P-selectin, thrombomodulin, tissue plasminogen activator (TPA), plasminogen activator inhibitor-1 (PAI-1), soluble fibrin monomer complex (SFMC), platelet-derived microparticles (PDMP), β-thromboglobulin, antithrombin and protein C. The main objective of our study was to investigate which part of the hemostatic system was mostly affected at the admission of Covid-19 patients and whether these parameters could differentiate intensive care unit (ICU) and non-ICU patients. Patients and Methods:In this prospective case-control study, 51 patients ≥18 years who are hospitalized with the diagnosis of Covid-19 and 21 healthy control subjects were included. We divided the patients into two groups according to their medical progress, either into ICU and non-ICU group. Regarding the outcome, patients were again categorized as survivor and non-survivor groups. Blood samples were collected from patients at admission at the time of hospitalization before administration of any treatment for Covid-19. The analyzes of the study were made with the IBM SPSS V22 program. p < 0.05 was considered statistically significant.Results:A total of 51 adult patients (F/M: 24/27) (13 ICU and 38 non-ICU) were included in the study cohort. The mean age of the patients was 68.1 ± 14.4 years. The control group consisted of 21 age and sex-matched healthy individuals. All of the patients were hospitalized, in a group of 13 patients, Covid-19 progressed to severe form and were hospitalized at ICU. We found out that the levels of fibrinogen, prothrombin time (PT), endothelial protein-C receptor (EPCR), D-dimer, soluble E-selectin, soluble P-selectin, plasminogen activator inhibitor-1 (PAI-1), and tissue plasminogen activator (TPA) were increased; whereas, the levels of soluble fibrin monomer complex (SFMC), platelet-derived microparticles (PDMP), antithrombin and protein-C were decreased in Covid-19 patients compared to the control group at hospital admission. Tissue plasminogen activator was the only marker that had a significantly different median level between ICU and non-ICU groups (p<0.001).Conclusions:In accordance with the previous literature, we showed that Covid-19 associated coagulopathy is distinct from sepsis-induced DIC with prominent early endothelial involvement and fibrinolytic shut-down. Reconstruction of endothelial function at early stages of infection may protect patients to progress to ICU hospitalization. We believe that after considering the patient’s bleeding risk, early administration of LMWH therapy at Covid-19 even in at outpatient setting may be useful both for restoring endothelial function and anticoagulation. The intensity of anticoagulation in non-ICU and ICU Covid-19 patients should be clarified with further studies.

Association of Plasminogen Activator Inhibitor-1 Gene Polymorphisms and Methylene Tetrahydrofolate Reductase Polymorphisms with Spontaneous Miscarriages

2017 ◽  
Vol 138 (2) ◽  
pp. 111-115
Author(s):  
Petra Bubalo ◽  
Iva Buterin ◽  
Zrinko Šalek ◽  
Vesna Ðogić ◽  
Silva Zupančić-Šalek
Keyword(s):  
Plasminogen Activator ◽  
Statistical Significance ◽  
Plasminogen Activator Inhibitor ◽  
Control Group ◽  
Plasminogen Activator Inhibitor 1 ◽  
Mthfr Polymorphisms ◽  
Methylene Tetrahydrofolate Reductase ◽  
Methylene Tetrahydrofolate ◽  
Activator Inhibitor ◽  
Pai 1

Aim: The objective of this study was to investigate a possible correlation between the plasminogen activator inhibitor-1 (PAI-1) and methylene tetrahydrofolate reductase (MTHFR) polymorphisms and unexplained spontaneous miscarriages (SM). Materials and Methods: PAI-1 polymorphisms were evaluated in 150 women with pregnancy in their history. One hundred women with a history of SM formed the study group and 50 women with normal pregnancies served as the control group. Also, the combination of PAI-1 and MTHFR polymorphisms were evaluated in 138 women out of a total of 150, which included 92 women with SM in their history compared to 46 women in the control group. For statistical analysis, χ2 test, Phi, and Cramer V tests were used; p < 0.05 was taken as a statistically significant result. Results: Our findings show: (a) the correlation between SM and PAI-1 mutations reaches statistical significance (p = 0.026); (b) there was a statistically significant difference between heterozygous PAI-1 in women with only 1 SM compared to the control group (p = 0.047); (c) the comparison of combinations of both mutations, PAI-1 and MTHFR, with the control group demonstrates statistical significance in favor of women with SM and both mutations (p = 0.022). Conclusion: PAI-1 and MTHFR polymorphisms may play an important role in pregnancy complications because heterozygous PAI-1 mutations and a combination of both PAI-1 and MTHFR mutations might contribute to SM.

scholarly journals Plasminogen activator inhibitor-1 in the evolution of stroke

2004 ◽  
Vol 132 (5-6) ◽  
pp. 143-147 ◽  
Author(s):  
Zagorka Jovanovic ◽  
Mirka Ilic ◽  
Jasna Zidverc-Trajkovic ◽  
Aleksandra Pavlovic ◽  
Milija Mijajlovic ◽  
...  
Keyword(s):  
Acute Stroke ◽  
Plasminogen Activator ◽  
Fibrinolytic Activity ◽  
Plasminogen Activator Inhibitor ◽  
Control Group ◽  
Plasminogen Activator Inhibitor 1 ◽  
Computed Tomography Scanning ◽  
Activator Inhibitor ◽  
Pai 1

Fibrinolytic activity in the acute stroke was examined by monitoring the level of plasminogen activator inhibitor-1 (PAI-1), as one of the indicators of fibrinolytic activity. Given the role of PAI-1 in the processes of atherogenesis and thrombogenesis, plasma PAI-1 level was measured in 59 patients (up to 50 years of age) with atherothrombotic stroke (verified by computed tomography scanning or magnetic resonance imaging of brain) in the period from 12 to 24 hours (I analysis) and 30 days after the onset of stroke (II analysis); then, it was correlated with plasma PAI-1 level in the control group (57 healthy subjects), which was 2.86?0.70 U/ml. It was found that PAI-1 level was significantly higher in the acute stroke (I analysis: PAI-1 =4.10?1.40 U/ml, p<0.001; II analysis: PAI-1 =3.64+0.90 U/ml, p<0.001), while fibrinolytic activity was lower, especially on the first day from the stroke that was not completely increased even after 30 days. There was no difference in PAI-1 levels between the subgroups of patients with infarction and lacunar cerebral ischemia (p>0.05), as well as between females and males (p>0.05). Along with significantly increased fibrinogen level (4.65?1 g/l, in the controls - 2.83?0.64 g/l, p<0.001), significantly higher triglycerides (2.04?0.76 mmol/l, in the controls - 1.38+0.54 mmol/l, p<0.001) and lipoproteins(a) (0.405?0.29 g/l, in the controls -0.172?0.14 g/l, p<0.001) were found, correlating with higher plasma PAI-1 level in these patients. The increased plasma level of PAI-1 pointed to possibility of decreased fibrinolytic activity in pathogenesis of ischemie stroke, as well as, risk of reinsult, which had been the greatest after the onset of stroke and declined gradually within several weeks.

scholarly journals Association of Plasminogen Activator Inhibitor-1 and Cardiovascular Events Development in Patients with Prediabetes

2021 ◽  
Vol 9 (B) ◽  
pp. 726-733
Author(s):  
Yelena Laryushina ◽  
Viktoriya Parakhina ◽  
Lyudmila Turgunova ◽  
Dinara Sheryazdanova ◽  
Raushan Dosmagambetova ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Cardiovascular Events ◽  
Fasting Glucose ◽  
Plasminogen Activator Inhibitor ◽  
Control Group ◽  
Homa Index ◽  
Plasminogen Activator Inhibitor 1 ◽  
C Peptide ◽  
Activator Inhibitor ◽  
Pai 1

Background. Plasminogen activator inhibitor-1(PAI-1) is a marker of endothelial dysfunction(ED) and a predictor of both the development of type 2 diabetes mellitus, and a cardiovascular event(CVE). Its role in the CVE development was sufficiently studied in patients without carbohydrate metabolism disorders, and understudied in patients with prediabetes. Aim: the research interest is the study of PAI-1 in patients with prediabetes and its effect on the CVE development. Materials and methods. The case-control study of 168 patients aged from 18 to 65 was carried out among the local population from January to December 2019.After clinical examination, patients were divided into 3 groups: group 1 (n=55)– patients with prediabetes and with CVE; group 2 (n=93) - patients with prediabetes and without CVE; the control group n=20. Results. Differences in PAI-1 level were found in groups 1 (Me=30718.6 pg/ml) and 2 (Me=24692.0 pg/ml; p≤0.001), even greater differences were found in both groups compared to the control one (p≤0.001). The correlation analysis has found in both group influence such IR indicators as fasting glucose, IR-HOMA index, glucagon, C-peptide to elevation of PAI-1. These findings indicate that with an elevation of the PAI-1 level, the concentration of fasting glucose, glucagon, C-peptide and scores of IR-HOMA index increase in both group. The Binary regression analysis has demonstrated, that an elevation of the PAI-1 biomarker increases the likelihood of CVE by 3.3 fold in patients with prediabetes (p≤0.01). In addition to, a model has been derived for assessing the risk of cardiovascular events in patients with prediabetes. Conclusions. Elevation of PAI-1 concentration is associated with insulin resistance which leads to ED, and further development risk of CVE in patients with prediabetes.

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 Prevention of Renal Fibrin Deposition in Endotoxin-induced DIC through Inhibition of PAI-1

2000 ◽  
Vol 84 (07) ◽  
pp. 65-70 ◽  
Author(s):  
Ramón Montes ◽  
Paul Declerck ◽  
Alfonso Calvo ◽  
Marta Montes ◽  
José Hermida ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Plasminogen Activator ◽  
Disseminated Intravascular Coagulation ◽  
Plasminogen Activator Inhibitor ◽  
Control Group ◽  
Fibrin Deposition ◽  
Plasminogen Activator Inhibitor 1 ◽  
Activator Inhibitor ◽  
Pai 1

SummaryPlasminogen activator inhibitor-1 (PAI-1) increases in endotoxemia thus possibly cooperating in altering the hemostatic balance in a prothrombotic direction. The effect of the inhibition of PAI-1 with the monoclonal antibody MA-33B8 was studied systemically and in kidneys in a lapine model of endotoxin-induced disseminated intravascular coagulation (DIC). The increase in plasmatic PAI activity in the control group (n = 9) was inhibited in the MA-33B8 treated rabbits (n = 5). Control rabbits showed renal fibrin deposits, whereas only one of the MA-33B8 rabbits did so. These results were confirmed immunohistochemically in kidneys as PAI-1 immunostaining was seen inside the glomeruli and larger vessels in the control group, whereas MA-33B8 rabbits showed a remarkable decrease, demonstrating that MA-33B8 successfully inhibited PAI-1 in the kidneys as well. Therefore evidence for the important role of PAI-1 in fibrin generation in endotoxin-induced DIC is presented, suggesting that strategies aiming at its reduction can be useful in this pathology.

scholarly journals The prevalence of 4G5G polymorphism of plasminogen activator inhibitor-1 (PAI-1) gene in polycystic ovarian syndrome and its association with plasma PAI-1 levels

2004 ◽  
pp. 793-798 ◽  
Author(s):  
E Diamanti-Kandarakis ◽  
G Palioniko ◽  
K Alexandraki ◽  
A Bergiele ◽  
T Koutsouba ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Dna Analysis ◽  
Fasting Glucose ◽  
Plasminogen Activator Inhibitor ◽  
Control Group ◽  
Total Testosterone ◽  
Plasminogen Activator Inhibitor 1 ◽  
Significant Difference ◽  
Activator Inhibitor ◽  
Pai 1

OBJECTIVE: To investigate the prevalence of 4G5G polymorphism of plasminogen activator inhibitor-1 (PAI-1) gene in polycystic ovary syndrome (PCOS) and its functional significance. DESIGN: Case-control study. METHODS: We studied 98 patients and 64 controls. Body mass index (BMI) and waist-to-hip (WHR) ratio were determined. Blood samples were obtained for DNA analysis. PAI-1 plasma levels, serum total testosterone, fasting insulin and fasting glucose were measured and the glucose-to-insulin ratio was estimated in all subjects. RESULTS: There was a statistically significant difference in the distribution of PAI-1 gene variations among the groups. The PCOS group had significantly higher 4G/4G and 4G/5G combinations than the control group, whereas there were significantly less 5G/5G. Among the PCOS women, 39.8% had the genotype 4G/4G, 39.8% 4G/5G and 20.4% 5G/5G. From the control group, 20.3% had genotype 4G/4G, 28.1% 4G/5G and 51.6% 5G/5G. In the 4G/4G genotype subgroup 75% were PCOS and 25% were controls, in the 4G/5G were 68.42% and 31.58% and in the 5G/5G were 31.58% and 62.26% respectively. The population of PCOS women had significantly higher PAI-1 levels, WHR, total testosterone, and fasting glucose than the population of controls. CONCLUSIONS: 1) The genotypic subtypes 4G/4G and 4G/5G, in PCOS, were present with a statistically higher frequency compared with controls. 2) PCOS women have higher levels of PAI-1 compared with the control group. 3) The presence of the 4G allele in PAI-1 promoter region of the gene further increases the PAI-1 levels.

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