scholarly journals Influence of PAI-1 Gene Promoter-675 (4G/5G) Polymorphism on Fibrinolytic Activity After Cardiac Surgery Employing Cardiopulmonary Bypass

Medicina ◽  
2012 ◽  
Vol 48 (10) ◽  
pp. 75
Author(s):  
Agnese Ozolina ◽  
Eva Strike ◽  
Inta Jaunalksne ◽  
Jelena Serova ◽  
Tatjana Romanova ◽  
...  
Keyword(s):  
Blood Loss ◽  
Plasminogen Activator ◽  
Postoperative Bleeding ◽  
Gene Promoter ◽  
Plasminogen Activator Inhibitor ◽  
University Hospital ◽  
Postoperative Blood Loss ◽  
Bleeding Volume ◽  
Pai 1 ◽  
D Dimer

Background and Objective. The plasminogen activator inhibitor type-1 (PAI-1) gene promoter contains 675 (4G/5G) polymorphism. The aim of this study was evaluate the effect of the PAI-1 promoter-675 (4G/5G) polymorphism on the concentrations of PAI-1 and tissue plasminogen activator/PAI-1 (t-PA/PAI-1) complex and bleeding volume after on-pump cardiac surgery.Material and Methods. A total of 90 patients were included in the study at Pauls Stradins Clinical University Hospital. Seven patients were excluded due to surgical bleeding. Eighty-three patients were classified according to the PAI-1 genotype: 21 patients had the 4G/4G genotype; 42, the 4G/5G genotype; and 20, the 5G/5G genotype. The following fibrinolysis parameters were recorded: the PAI-1 level preoperatively, D-dimer level at 0, 6, and 24 hours after surgery, and t-PA/ PAI-1 complex level 24 hours postoperatively. A postoperative bleeding volume was registered in mL 24 hours after surgery.Results. The patients with the 5G/5G genotype had significantly lower preoperative PAI-1 levels (17 [SD, 10.8] vs. 24 ng/mL [SD, 9.6], P=0.04), higher D-dimer levels at 6 hours (371 [SD, 226] vs. 232 ng/mL [SD, 185], P=0.03) and 24 hours (326 [SD, 207] vs. 209 ng/mL [SD, 160], P=0.04), and greater postoperative blood loss (568 [SD, 192] vs. 432 mL [168], P=0.02) compared with the 4G/4G carriers. There were no significant differences in the levels of the t-PA/PAI-1 complex comparing different genotype groups.Conclusions. The carriers of the 5G/5G genotype showed the lower preoperative PAI-1 levels, greater chest tube blood loss, and higher D-dimer levels indicating that the 5G/5G carriers may have enhanced fibrinolysis.

scholarly journals Postoperative Bleeding in Cardiac Surgery

2008 ◽  
Vol 108 (4) ◽  
pp. 596-602 ◽  
Author(s):  
Jose L. Iribarren ◽  
Juan J. Jimenez ◽  
Domingo Hernández ◽  
Maitane Brouard ◽  
Debora Riverol ◽  
...  
Keyword(s):  
Cardiopulmonary Bypass ◽  
Blood Loss ◽  
Plasminogen Activator ◽  
Chest Tube ◽  
Postoperative Bleeding ◽  
Plasminogen Activator Inhibitor ◽  
Plasminogen Activator Inhibitor 1 ◽  
Transfusion Requirements ◽  
Activator Inhibitor ◽  
Pai 1

Background Plasminogen activator inhibitor 1 (PAI-1) attenuates the conversion of plasminogen to plasmin. Polymorphisms of the PAI-1 gene are associated with varying PAI-1 levels and risk of prothrombotic events in nonsurgical patients. The purpose of this study, a secondary analysis of a clinical trial, was to investigate whether PAI-1 genotype affects the efficacy of tranexamic acid (TA) in reducing postoperative chest tube blood loss of patients undergoing cardiopulmonary bypass. Methods Fifty patients were classified according to PAI-1 genotype (4G/4G, 4G/5G, or 5G/5G). Twenty-four received 2 g TA before and after cardiopulmonary bypass, whereas 26 received placebo. The authors recorded data related to coagulation, fibrinolysis, and bleeding before surgery, at admission to the intensive care unit (0 h), and 4 and 24 h later. Results In patients not receiving TA, those with the 5G/5G genotype had significantly higher chest tube blood loss and transfusion requirements compared with patients with the other genotypes at all time points. Patients with the 5G/5G genotype receiving TA showed significantly lower blood loss compared with the placebo group. There were no significant differences in blood loss or transfusion requirements between patients with the 4G/4G genotype when TA was used. Conclusions Plasminogen activator inhibitor-1 5G/5G homozygotes who did not receive TA showed significantly greater postoperative bleeding than patients with other PAI-1 genotypes. 5G/5G homozygotes who received TA showed the greatest blood-sparing benefit.

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.

scholarly journals The Relationship Between Thrombo-Inflammatory Biomarkers and Cellular Indices of Inflammation in Lymphoma Patients

2021 ◽  
Vol 27 ◽  
pp. 107602962110503
Author(s):  
Mark Jaradeh ◽  
Nausheen Baig ◽  
Emily Bontekoe ◽  
Mirjana Mitrovic ◽  
Darko Antic ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Factor Xiii ◽  
Plasminogen Activator Inhibitor ◽  
Inflammatory Biomarkers ◽  
Kinetic Assay ◽  
Blood Profile ◽  
Inflammatory Biomarker ◽  
Tnf Α ◽  
Pai 1 ◽  
D Dimer

Introduction Thrombo-inflammatory biomarkers play an important role in the pathogenesis of lymphoma. We aimed to characterize the interrelationship of thrombo-inflammatory biomarkers and blood cellular indices in lymphoma patients. Materials and Methods Ninety-eight lymphoma patient samples were collected from Lymphoma Center of Clinic of Hematology, University of Belgrade, Serbia. Normal controls (n = 50) represented plasma from healthy individuals. Plasminogen activator inhibitor (PAI-1), D-Dimer, factor XIII, C-reactive protein (CRP), microparticles (Mp), Von Willebrand factor (vWF), total protein S, urokinase-type plasminogen activator (uPA), tumor necrosis factor (TNF α), β2-glycoprotein I ( β2GPI), and fibronectin levels were measured utilizing commercially-available ELISA methods. Thrombin generation profile (TGA) was measured using a fluorometric kinetic assay. Platelets, leukocytes, lymphocytes, and neutrophils were measured in conjunction with the complete blood profile. Results Statistically significant differences were noted in levels of PAI-1, D-Dimer, factor XIII, CRP, microparticles, vWF, uPA, TNF α, β2GPI, fibronectin, and TGA when compared to normal (all P values < .001). Platelet to leukocyte ratio (PLA) correlated to TNF α and fibronectin ( R = −0.31 and −0.53, respectively) and the platelet to neutrophil ratio (PNR) correlated to factor XIII and β2GPI ( R = 0.40 and 0.40, respectively). Conclusion Plasma samples from lymphoma patients demonstrated a significantly altered thrombo-inflammatory biomarker profile that has notable correlations to blood cellular indices.

scholarly journals 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.

2003 ◽  
Vol 50 (1) ◽  
pp. 279-289 ◽  
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.

Postoperative Hemostasis and Fibrinolysis in Patients Undergoing Cardiopulmonary Bypass with or without Aprotinin Therapy

1994 ◽  
Vol 72 (03) ◽  
pp. 438-443 ◽  
Author(s):  
He Lu ◽  
Charles Du Buit ◽  
Jeannette Soria ◽  
Bernard Touchot ◽  
Bernard Chollet ◽  
...  
Keyword(s):  
Placebo Group ◽  
Cardiopulmonary Bypass ◽  
Blood Loss ◽  
Plasminogen Activator ◽  
Fold Increase ◽  
Tissue Type ◽  
Postoperative Blood Loss ◽  
High Dose ◽  
Double Blind Study ◽  
Pai 1

SummaryIntra- and postoperative blood loss during open heart surgery is reduced by approximately 50% when aprotinin, a potent inhibitor for plasmin and kallikrein, is administered during surgery. But whether aprotinin increases the risk of thrombotic complications remains controversial. The aim of this study was to evaluate the effects of aprotinin administration on coagulation and fibrinolysis during and after cardiopulmonary bypass (CPB). Thirty patients undergoing CPB were randomly assigned to two comparable groups for a double-blind study (16 patients receiving high-dose aprotinin, 14 patients receiving placebo). Patients’ plasma levels of ATM (thrombin-induced modified antithrombin III), FbDP (fibrin degradation products, D-Dimers), t-PA (tissue-type plasminogen activator) and PAI-1 (plasminogen activator inhibitor type 1) were measured at regular intervals. In both groups, ATM level increased during surgery (from less than 30 to 90-110 ng/ml) and returned to normal 24 h after surgery and remained unchanged thereafter. Aprotinin reduced this increase in ATM levels (p = 0.02 at 30 min after the start of CPB). The FbDP generated during surgery was greatly reduced in the aprotinin group (945 ng/ml) in comparison with the placebo group (1889 ng/ml, p = 0.004). After surgery, FbDP levels decreased in both groups with nadirs at 2nd day (placebo group: 940 ng/ml and aprotinin group: 865 ng/ml) indicating a hypo-fibrinolytic period. Then, the FbDP level in both groups started to increase up to the 9th day, in an identical manner. This postoperative hypofibrinolysis is related to the changes of t-PA and PAI-1 levels: immediately after surgery there was a 2’fold increase in t-PA level and a 4-5 fold increase in PAI-1 level in the two groups. During the following 24 h, t-PA levels decreased in both groups. In contrast, PAI-1 levels in the placebo group during the same time increased sharply to a maximum level (175.7 ng/ml). This further increase did not occur in the aprotinin group although it remained at a high level (79.2 ng/ml). The difference in the increase of PAI-1 between the 2 groups (value at 24 h minus preoperative value: Dl-Tl) was significantly different (p = 0.04). Then t-PA continued to decrease and PAI-1 began to decrease steadily. Total blood loss was significantly reduced by aprotinin therapy (3.06 ml/kg versus 5.86 ml/kg). The present study confirms the inhibitory effects of aprotinin on both fibrinolytic activity and blood coagulation activation during CPB, and reveals an hypofibrinolytic period that lasts 48 h after surgery in both aprotinin and placebo groups. This inhibition of fibrinolysis is apparently associated with high PAI-1 level. The data of this study also show that 2 days after aprotinin therapy, there is no prolonged effect of aprotinin on fibrinolysis. In addition, the lower level of PAI-1 in the aprotinin group after surgery might result from a protection of endothelial cells by aprotinin, suggesting an unexpected benefit of aprotinin therapy.

Correlations between Plasminogen Activator Inhibitor-1 and Peritoneal Transport in Pediatric Ccpd Patients

1995 ◽  
Vol 15 (6_suppl) ◽  
pp. 246-251 ◽  
Author(s):  
Jen-Jar Lin ◽  
Kamal Singhal ◽  
Lance Parton ◽  
Clair Cascio ◽  
Clifford S. Patlak ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Surface Area ◽  
Body Surface Area ◽  
Body Surface ◽  
Plasminogen Activator Inhibitor ◽  
University Hospital ◽  
Plasminogen Activator Inhibitor 1 ◽  
Peritoneal Transport ◽  
Activator Inhibitor ◽  
Pai 1

Objective Plasminogen activator inhibitor-1 (PAI-1) is an important regulator of plasminogen activators and has been shown to be involved in the accumulation of extracellular matrix (ECM) in various tissues. Since peritoneal ECM is a resistance site for peritoneal transport, the production and release of PAI-1 in the peritoneum may affect the peritoneal transport of water and small solutes. Design The linear correlations between the dialysate PAI-1 levels and the variables of peritoneal transport during peritoneal equilibration tests (PET) wereexamined. .Setting A tertiary university hospital. Patients Six stable pediatric patients (age 10.8%4 years) undergoing continuous cycler-assisted peritoneal dialysis were included. Interventions None. Results All data are mean±SD. There was a positive correlation between the infused volume and the net ultrafiltration (UF, 198±127 mL, r = 0.82, p < 0.05). The dialysate PAI-1 levels increased during the dwell time (2.44±2.23 ng/mL or 2.46±1.72 μg at 4 hours vs 0.04±0.1 ng/mL or 0.04±0.09 μg at 0 hour, p < 0.05). The saturation indices (dialysate/plasma ratio) of PAI-1 and albumin at 4 hours were 1.05±1.21 and 0.028±0.004, respectively. The changes from O-hour dwell to 4-hour dwell in the dialysate PAI-1 concentration (PAI4-o, 2.4±2.2 ng/mL) or amount corrected to body surface area (APAI4-0/BSA, 2.61 ±2.11μg/ m2) negatively correlated with UF or UF/body surface area and positively correlated with the number of episodes of peritonitis. There was no correlation between PAI4-o, APAI4-0/BSA, or plasma PAI-1 concentration and the mass transfer coefficient and clearance of either urea or creatinine. Conclusions The elevated PAI-1 level during the PET was likely from the local production and release of PAI-1. It had an inverse relationship with the amount of ultrafiltration. Repeated inflammation of the peritoneum was associated with an increased production and release of PAI-1 into the peritoneum.

Haemostatic activation and Inflammatory response after three methods of treatment of great saphenous vein incompetence

2013 ◽  
Vol 29 (3) ◽  
pp. 154-163 ◽  
Author(s):  
L Dzieciuchowicz ◽  
G Espinosa ◽  
J A Páramo
Keyword(s):  
Inflammatory Response ◽  
Plasminogen Activator ◽  
Saphenous Vein ◽  
Great Saphenous Vein ◽  
Statistical Significance ◽  
Plasminogen Activator Inhibitor ◽  
High Ligation ◽  
Methods Of Treatment ◽  
Pai 1 ◽  
D Dimer

Objective: The purpose of this study was to compare the activation of haemostasis and inflammatory response after three different methods of treatment of great saphenous vein (GSV) incompetence. Material and methods: Forty-five patients with GSV incompetence were assigned to one of the three types of treatment: high ligation and stripping (HL&S), radiofrequency ablation with ClosureFast (RFA) and endovenous laser ablation (EVLA) with 810 nm diode laser with miniphlebectomy if required. Peripheral blood samples were obtained in the morning before the surgery and 24 hours and 10 days after the procedure. The concentrations of C-reactive protein (CRP), D-dimer, prothrombin fragment 1+2 (F1 + 2), antigen of tissue plasminogen activator (t-PA) and von Willebrand factor (vWF) antigen and activity of plasminogen activator inhibitor (PAI-1) were determined. The results were statistically analysed with SPSS for Windows 15.0. Results: Thirty-eight patients completed the study: 13 from RFA, 14 from EVLA and 11 from HL&S group. The baseline data did not differ among groups. There was a significant increase of D-dimer in HL&S group after 24 hours ( P = 0.002). The changes in RFA and EVLA groups did not show statistical significance ( P = 0.092). PAI-1 decreased in RFA patients after 24 hours ( P = 0.02), did not change in EVLA patients, and tended to increase after HL&S (P = 0.08). The highest CRP increase was observed in HL&S group ( P = 0.003). No significant changes in F1 + 2, t-PA and vWF were observed in any group of patients at 24 hours. At 10 days, a further significant increase of D-dimer ( P = 0.04) and CRP ( P = 0.018) concentrations in HL&S but not RFA and EVLA patients was observed. Conclusions: Endovenous thermal ablation is associated with significantly less activation of haemostasis and inflammatory response when compared with HL&S.

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