The predictive value of plasminogen activator inhibitor-1, fibrinogen, and D-dimer for deep venous thrombosis following surgery for traumatic lower limb fracture

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.

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First Use of a Novel Inhibitor of Plasminogen Activator Inhibitor 1 (MDI-2268) in Animal Model of Deep Venous Thrombosis and Attempts of Combined Antithrombotic Therapy

Journal of Vascular Surgery Venous and Lymphatic Disorders ◽

10.1016/j.jvsv.2019.12.006 ◽

2020 ◽

Vol 8 (2) ◽

pp. 309-310

Author(s):

Maxim Shaydakov ◽

Joshua Rainey ◽

Daniel Lawrence ◽

Jose Diaz

Keyword(s):

Animal Model ◽

Venous Thrombosis ◽

Deep Venous Thrombosis ◽

Plasminogen Activator ◽

Antithrombotic Therapy ◽

Plasminogen Activator Inhibitor ◽

Plasminogen Activator Inhibitor 1 ◽

Activator Inhibitor ◽

Inhibitor Of Plasminogen Activator

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THE FIBRINOLYTIC ALTERATION ASSOCIATED WITH DAILY ADMINISTRATION OF SILDENAFIL

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2018.v11i8.23144 ◽

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.

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Association between the plasminogen activator inhibitor-1 4G/5G polymorphism and venous thrombosis

Thrombosis and Haemostasis ◽

10.1160/th06-12-0745 ◽

2007 ◽

Vol 97 (06) ◽

pp. 907-913 ◽

Cited By ~ 56

Author(s):

Argirios Tsantes ◽

Pantelis Bagos ◽

Evdoxia Rapti ◽

Georgios Mantzios ◽

Violeta Kapsimali ◽

...

Keyword(s):

Risk Factor ◽

Venous Thrombosis ◽

Plasminogen Activator ◽

Genetic Risk ◽

Plasminogen Activator Inhibitor ◽

Genetic Risk Factor ◽

Published Data ◽

Antiphospholipid Antibody ◽

Plasminogen Activator Inhibitor 1 ◽

Activator Inhibitor

SummaryThe effect of the 675 insertion/deletion (4G/5G) polymorphism of plasminogen activator inhibitor-1 (PAI-1) gene on the risk of venous thromboembolism (VTE) remains controversial. In this study, we performed a meta-analysis of published data regarding this issue. A comprehensive electronic search was carried out up until September 2006. A total of 22 articles were included in the analysis that was performed using random effects models. Eighteen papers, concerning patients without another known risk factor, comprised 2,644 cases and 3,739 controls. The alleles contrast (4G vs. 5G allele) yielded a statistically significant odds ratio (OR) of 1.153 (95% confidence interval [CI]: 1.068–1.246). In a sub-analysis of five studies that included 256 cases with another genetic risk factor and 147 controls, the combined per-allele OR was still significant (OR:1.833,95% CI:1.325–2.536). On the contrary, the analysis of five studies regarding cases with a non-genetic risk factor for VTE (antiphospholipid antibody syndrome, Behcet disease) provided insignificant results in all aspects. There was no evidence for heterogeneity and publication bias in all analyses. Based on our findings, the 4G allele appears to increase the risk of venous thrombosis, particularly in subjects with other genetic thrombophilic defects. Recommendation for detection of this polymorphism in evaluating thrombophilia in such patients might be considered.

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Continuous Active State of Coagulation System in Patients With Nonthrombotic Inflammatory Bowel Disease

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/1076029611405034 ◽

2011 ◽

Vol 17 (6) ◽

pp. 600-604 ◽

Cited By ~ 23

Author(s):

Huseyin Alkim ◽

Selime Ayaz ◽

Canan Alkim ◽

Aysel Ulker ◽

Burhan Sahin

Keyword(s):

Plasminogen Activator ◽

Degradation Products ◽

Plasminogen Activator Inhibitor ◽

Protein S ◽

Plasminogen Activator Inhibitor 1 ◽

Inflammatory Bowel ◽

Von Willebrand ◽

Willebrand Factor ◽

Activator Inhibitor ◽

D Dimer

This study was planned for searching possible changes of the total coagulation and fibrinolysis system in inflammatory bowel disease (IBD) in order to obtain some clues for explaining the relation between IBD and hypercoagulability. A total of 24 patients with ulcerative colitis, 12 patients with Crohn disease, and 20 healthy controls were studied. Platelets; prothrombin time (PT); partial thromboplastin time (PTT); fibrinogen; d-dimer; fibrinogen degradation products; protein C; protein S; antithrombin; thrombin time; von Willebrand factor; coagulation factors V, VII, VIII, IX, XI, and XIII; plasminogen; antiplasmin; tissue plasminogen activator; plasminogen activator inhibitor 1; and prothrombin fragments 1 + 2 were studied. Most of the procoagulants (platelets, fibrinogen, von Willebrand factor, coagulation factor IX, and plasminogen activator inhibitor 1) were found increased together with decreases in some anticoagulants (protein S and antithrombin) in IBD. Also the activation markers of coagulation (d-dimer, fibrinogen degradation products, and prothrombin fragments 1 + 2) were all increased. The parameters of the total coagulation–fibrinolysis system were increased in IBD, regardless of the form and the activity of the disease.

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Incidence of increased plasminogen activator inhibitor in patients with deep venous thrombosis and/or pulmonary embolism

Thrombosis Research ◽

10.1016/0049-3848(89)90242-9 ◽

1989 ◽

Vol 56 (4) ◽

pp. 565-570 ◽

Cited By ~ 23

Author(s):

M.Dolores Tabernero ◽

Amparo Estellés ◽

Vicente Vicente ◽

Ignacio Alberca ◽

Justo Aznar

Keyword(s):

Pulmonary Embolism ◽

Venous Thrombosis ◽

Deep Venous Thrombosis ◽

Plasminogen Activator ◽

Plasminogen Activator Inhibitor ◽

Activator Inhibitor

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Fibrin D-dimer impairs the accumulation and anticoagulant properties of heparan sulphate and stimulates secretion of plasminogen activator inhibitor-1 by rabbit coronary endothelial cells.

Acta Biochimica Polonica ◽

10.18388/abp.2003_3737 ◽

2003 ◽

Vol 50 (1) ◽

pp. 279-289 ◽

Cited By ~ 2

Author(s):

Natalia Yu Yevdokimova ◽

Larisa D Veselovska ◽

Genrietta K Gogolinska ◽

Olexandra M Buchanevich ◽

Galina V Kosyakova ◽

...

Keyword(s):

Endothelial Cells ◽

Plasminogen Activator ◽

Heparan Sulphate ◽

Plasminogen Activator Inhibitor ◽

No Production ◽

Plasminogen Activator Inhibitor 1 ◽

Coronary Endothelial Cells ◽

Activator Inhibitor ◽

Pai 1 ◽

D Dimer

Fibrin split product D-dimer (DD) is most probably involved in the development of vascular disorders. At 1.5 microM concentration DD inhibited the incorporation of D-[1-(3)H]glucosamine hydrochloride and [2-(14)C]acetate x Na into pericellular heparan sulphate (HS) of rabbit coronary endothelial cells without affecting other groups of glycosaminoglycans (GAGs). At the same time, DD reduced HS ability to bind antithrombin (AT) and suppressed NO production. The effect of DD on pericellular GAGs was similar to that of N(omega)-methyl-L-arginine, the competitive inhibitor of endothelial NO synthase (eNOS). L-Ascorbic acid, eNOS activator, increased the level of endogenous NO in the DD-treated cells, and restored HS accumulation and antithrombin binding. It is suggested that DD influence on endothelial HS may be mediated by NO production. Another effect of DD, namely, stimulation of plasminogen activator inhibitor-1 (PAI-1) secretion did not depend on the NO level. The decreased HS content, reduced anticoagulant properties of HS, and increased PAI-1 secretion disorganized the endothelial matrix, and promoted fibrin formation and vascular damage. This points to DD as an important factor in the development of vascular disorders.

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Specific Polymorphism 4G/5G Gene for PAI-1 as a Possible Cause of Cerebral Venous Thrombosis: A Case Report

Serbian Journal of Experimental and Clinical Research ◽

10.1515/sjecr-2016-0038 ◽

2017 ◽

Vol 18 (2) ◽

pp. 169-173

Author(s):

Tatjana Boskovic Matic ◽

Aleksandar Gavrilovic ◽

Snezana Simovic ◽

Dejan Aleksic ◽

Katarina Vesic ◽

...

Keyword(s):

Venous Thrombosis ◽

Plasminogen Activator ◽

Cerebral Venous Thrombosis ◽

Sinus Thrombosis ◽

Plasminogen Activator Inhibitor ◽

Plasminogen Activator Inhibitor 1 ◽

Sagittal Sinus ◽

Clinical Center ◽

The Impact ◽

Activator Inhibitor

AbstractThrombosis of veins and venous sinus (CVT) is the rare cerebral vascular disorder which makes less than 1% of all strokes. Thrombosis of veins and venous sinuses is picturesquely called “мајоr neurological forger” since it is characterized by very varied clinical picture. Among the various causes of CVT, which can be of infective or non-infective nature, the congenital hyper coagulations especially stand out, diagnosis is based on highly sophisticated diagnostic tests.We present the case of a female patient, 36 years old, who was hospitalized at the Clinic for Neurology in Clinical Center because of the diffuse headache she had for the last few days, with milder right-sided hemiparesis and one generalized tonic-clonic epileptic seizure. With nuclear magnetic resonance (MR/2D venography) the thrombosis of the upper and lower sagittal sinuses is confirmed. By appropriate laboratory tests, as well as by confirmatory immunological and genetic analyses, the impact of the most of the factors is excluded which can contribute to the occurrence of venous thrombosis. The only pathological findings which indicated the possible congenital thrombophilia as the cause of the sagittal sinus thrombosis was the determination of the specific polymorphism of the 4G/5G gene for plasminogen activator inhibitor 1.According to our knowledge, this is the first decribed case of the possible impact of the specific polymorphism of the 4G/5G gene for plasminogen activator inhibitor of 1 on the development of cerebral venous thrombosis.

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