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 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 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 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.

TNF-α and insulin, alone and synergistically, induce plasminogen activator inhibitor-1 expression in adipocytes

1999 ◽  
Vol 276 (6) ◽  
pp. C1391-C1397 ◽  
Author(s):  
Tomohiro Sakamoto ◽  
Janet Woodcock-Mitchell ◽  
Kousuke Marutsuka ◽  
John J. Mitchell ◽  
Burton E. Sobel ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Synergistic Effects ◽  
Plasminogen Activator Inhibitor ◽  
Plasminogen Activators ◽  
System Capacity ◽  
Plasminogen Activator Inhibitor 1 ◽  
Tnf Α ◽  
Factor Α ◽  
Activator Inhibitor ◽  
Pai 1

Obesity is associated with hyperinsulinemia and elevated concentrations of tumor necrosis factor-α (TNF-α) in adipose tissue. TNF-α has been implicated as an inducer of the synthesis of plasminogen activator inhibitor-1 (PAI-1), the primary physiological inhibitor of fibrinolysis, mediated by plasminogen activators in cultured adipocytes. To identify mechanism(s) through which TNF-α induces PAI-1, 3T3-L1 preadipocytes were differentiated into adipocytes and exposed to TNF-α for 24 h. TNF-α selectively increased the synthesis of PAI-1 without increasing activity of plasminogen activators. Both superoxide (generated by xanthine oxidase plus hypoxanthine) and hydrogen peroxide were potent inducers of PAI-1, and hydroxyl radical scavengers completely abolished the TNF-α induction of PAI-1. Exposure of adipocytes to TNF-α or insulin alone over 5 days increased PAI-1 production. These agonists exert synergistic effects. Results obtained suggest that TNF-α stimulates PAI-1 production by adipocytes, an effect potentiated by insulin, and that adipocyte generation of reactive oxygen centered radicals mediates the induction of PAI-1 production by TNF-α. Because induction of PAI-1 by TNF-α is potentiated synergistically by insulin, both agonists appear likely to contribute to the impairment of fibrinolytic system capacity typical in obese, hyperinsulinemic patients.

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.

Fibrin Fragment Induction of Plasminogen Activator Inhibitor Transcription Is Mediated by Activator Protein-1 Through a Highly Conserved Element

Blood ◽  
1999 ◽  
Vol 94 (6) ◽  
pp. 2029-2038 ◽  
Author(s):  
Mitchell A. Olman ◽  
James S. Hagood ◽  
Warren L. Simmons ◽  
Gerald M. Fuller ◽  
Charles Vinson ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Transcriptional Activity ◽  
Plasminogen Activator Inhibitor ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Activator Protein 1 ◽  
Activator Protein ◽  
Activator Inhibitor ◽  
Pai 1 ◽  
D Dimer

Abstract Plasminogen activator inhibitor type-1 (PAI-1), a serine protease inhibitor, affects the processes of fibrinolysis, wound healing, and vascular remodeling. We have demonstrated that PAI-1 transcription is induced by D dimer, a plasmin proteolytic fragment of fibrin, supporting its role in negative feedback on peri-cellular proteolysis. The focus of this study was to define the mechanism of D dimer’s effects on PAI-1 transcription. D dimer increased the binding activity of the transcription factor activator protein-1 components c-fos/junD and c-fos mRNA levels in a time- and concentration-dependent manner to a greater extent than fibrinogen. Both basal and D dimer-induced PAI-1 transcriptional activity were entirely dependent on elements within the −161 to −48 bp region of the PAI-1 gene in fibroblasts. Mutations within the AP-1–like element (−59 to −52 bp) in the PAI-1 gene affected D dimer-induced transcriptional activity, c-fos/junD DNA binding, and basal and c-fos inducible PAI-1 transcriptional activity. Furthermore, expression of either wild-type or mutant c-fos proteins augmented or diminished the response of the PAI-1 promoter (−161 to +26 bp) to D dimer, respectively. D dimer-induced binding of c-fos/junD to the highly conserved and unique AP-1 like element in the PAI-1 gene provides a mechanism whereby specific fibrin fragments control fibrin persistence at sites of inflammation, fibrosis, and neoplasia.

Types 1 and 2 Plasminogen Activator lnhibitor and Tirmor Necrosis Factor Alpha in Fatients with Sepsis

1990 ◽  
Vol 64 (01) ◽  
pp. 003-006 ◽  
Author(s):  
J A Páramo ◽  
J L Pérez ◽  
M Serrano ◽  
E Rochal
Keyword(s):  
Plasminogen Activator ◽  
Plasma Concentrations ◽  
Plasminogen Activator Inhibitor ◽  
Necrosis Factor Alpha ◽  
Human Sepsis ◽  
Tnf Α ◽  
Gram Negative Bacteremia ◽  
Activator Inhibitor ◽  
Necrosis Factor ◽  
Pai 1

SummaryWe have determined the plasma concentrations of types 1 and 2 of plasminogen activator inhibitor (PAI-1 and PAI-2), tumor necrosis factor (TNF-α) and endotoxin in 47 patients with bacterial infection (22 patients presented with positive blood cultures). Results were compared with those observed in 30 healthy subjects. There was a significant increase in PAI-1 and TNF-α in patients as compared to controls (p <0.0001), whereas no differences for PAI-2 were observed. PAI-1 and TNF-α were significantly higher in 18 patients with gram-negative bacteremia as compared to all other patients (p <0.0001). However, no correlation between the analyzed parameters and either endotoxin or clinical outcome was observed. We conclude that there is an increase of PAI-1 and TNF-α in patients with sepsis, which is not related to the endotoxin concentration. Our results suggest that PAI-1, but not PAI-2, is the main plasminogen activator inhibitor in human sepsis.

Increased Mononuclear Cell Tissue Factor and Type-2 Plasminogen Activator Inhibitor and Reduced Plasma Fibrinolytic Capacity in Children with Lymphoma

1994 ◽  
Vol 72 (01) ◽  
pp. 054-057 ◽  
Author(s):  
N Semeraro ◽  
P Montemurro ◽  
P Giordano ◽  
N Santoro ◽  
D De Mattia ◽  
...  
Keyword(s):  
Tissue Factor ◽  
Plasminogen Activator ◽  
Blood Clotting ◽  
Mononuclear Cells ◽  
Plasminogen Activator Inhibitor ◽  
Tissue Type ◽  
Fibrin Deposition ◽  
Activator Inhibitor ◽  
Pai 1 ◽  
D Dimer

SummaryBlood clotting activation and fibrin deposition are common findings in lymphoma patients. We evaluated the capacity of peripheral blood mononuclear cells to produce procoagulant activity (PCA) and plasminogen activator inhibitor (PAI) in 12 children with newly diagnosed lymphoma (8 non-Hodgkin’s, 4 Hodgkin’s) and in 12 matched healthy donors. In the same subjects we also measured plasma antigen levels of tissue-type PA (t-PA), urokinase-type PA (u-PA), PAI-1, PAI-2, and D-dimer. PCA generated by mononuclear cells after incubation for 20 h at 37° C was significantly higher in patients than in controls (p = 0.027). In all samples it was identified as tissue factor by functional criteria (dependence on factor VII). Moreover, culture medium obtained from patients’ mononuclear cells after incubation for 20 h at 37° C contained significantly higher amounts of PAI activity and PAI-2 antigen than control samples (p <0.001). Plasma PAI-1 and t-PA antigens were significantly augmented in patients (p <0.005), the mean increase of PAI-I being about 5 times higher than that of t-PA. Plasma levels of D-dimer wete markedly increased in the patients’ group (p <0.001), whereas u-PA and PAI-2 antigens did not differ from controls. It is suggested that monocytes from lymphoma patients are endowed with functional abnormalities leading to the simultaneous expression of tissue factor and antifibrinolytic activity. These abnormalities, coupled with a reduced plasma fibrinolytic potential, could play an important pathogenetic role in blood clotting activation and fibrin deposition associated with lymphoma.

scholarly journals Combined presence of coagulation factor XIII V34L and plasminogen activator inhibitor 1 4G/5G gene polymorphisms significantly contribute to recurrent pregnancy loss in serbian population

2019 ◽  
Vol 0 (0) ◽  
Author(s):  
Ivana Joksic ◽  
Zeljko Mikovic ◽  
Dejan Filimonovic ◽  
Jelena Munjas ◽  
Natasa Karadzov Orlic ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Gene Polymorphisms ◽  
Factor Xiii ◽  
Pregnancy Loss ◽  
Recurrent Pregnancy Loss ◽  
Plasminogen Activator Inhibitor ◽  
Plasminogen Activator Inhibitor 1 ◽  
History Of ◽  
Activator Inhibitor ◽  
Pai 1

SummaryBackgroundRecurrent pregnancy loss (RPL) is a heterogeneous condition affecting up to 5% of women of reproductive age. Inherited thrombophilia have been postulated as one of the causes of RPL. Here we examined the prevalence of nine thrombophilic gene polymorphisms among women with history of recurrent miscarriages and fertile controls.MethodsThe study included 70 women with history of at least three early pregnancy losses and 31 fertile controls with no miscarriages. We investigated mutations in genes responsible for clotting and fibrinolysis, including factor V (FV) Leiden, FV H1299R, factor II (FII) G20210A, methylene tetrahydrofolate reductase (MTHFR) C677T and A1298C, factor XIII (FXIII) V34L, plasminogen activator inhibitor-1 (PAI-1) 4G/5G and endothelial protein C receptor (EPCR) H1 and H3 haplotypes using reverse polymerase chain reaction ViennaLab cardiovascular disease StrippAssays.ResultsOur results showed no significant increase in prevalence of tested polymorphisms in women with RPL. However, relative risk for PRL among women heterozygous for FXIII V34L was 2.81 times increased (OR 2.81, 95% CI 1.15–6.87, P=0.023). Haplotype analysis showed that combined presence of high-risk genotypes for FXIII and PAI-1 significantly increases risk for RPL (OR 13.98, CI 95% 1.11–17.46, P=0.044).ConclusionsThis is the first study in Serbian population that investigated prevalence of FVR2, A1298C, FXIII V34L and EPCR gene variants. Compound heterozygosity for FXIII V34L and PAI-1 4G is significant risk factor for recurrent miscarriage. Our results should be viewed in context of small case-control study, so further large prospective studies are need for confirmation of our findings.

Thrombolysis, With or Without Heparin, During the First Nine Weeks After Acute Myocardiat Infarction

1997 ◽  
Vol 3 (3) ◽  
pp. 183-189
Author(s):  
W. Pickering ◽  
M. Brozovic ◽  
M. Dancy ◽  
H. Cohen
Keyword(s):  
Myocardial Infarction ◽  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Recombinant Tissue Plasminogen Activator ◽  
Activity Levels ◽  
Fibrin Plate ◽  
Rebound Increase ◽  
Key Words Thrombolysis ◽  
Pai 1 ◽  
D Dimer

The duration and characteristics of fibrinolytic "shut-down" were studied in 40 patients serially for a 9-week period after acute myocardial infarction (AMI). Patients were randomized into four equal groups to receive streptokinase (SK), SK plus heparin (SK + H), recombinant tissue plasminogen activator (rt-PA) or recombinant t-PA plus heparin (rt-PA + H). All patients received oral aspirin. Plasma fibrinolysis was assessed by performance of the following tests: fibrin plate lysis (FPL), tissue plas. minogen activator (t-PA) activity and t-PA antigen (Ag), plasminogen (plg) and α2-antiplasmin (α2-AP) activity, Clauss fibrinogen, and D-dimer. Prethrombolysis global fibrinolysis was normal in most patients, although plasminogen activator inhibitor (PAI) activity and PA inhibitor-1 antigen (PAI-I Ag) were increased 37.5% of the patients. Fibrin plate lysis was significantly decreased for the first 48 h in all four groups (p < 0.05-0.002) compared with normal controls (n = 10); the decrease persisted longest (5 days) in the group receiving rt-PA alone. The decreased fibrin plate lysis was accompanied by significantly increased D-dimer levels (p < 0.003-0.0002) as well as decreased plg and α2-AP activities (p < 0.05-0.0002), which persisted longer. (≤72 h) in patients receiving SK, indicating a more widespread activation of fibrinolysis in this group. Fibrinogen levels showed a rebound increase which began ≤24 h after thrombolysis while levels of plg and a2-AP were at their lowest. The fibrinogen rebound persisted for at least 6 weeks (p < 0.05-0.002). t-PA activity remained unchanged, and t-PA Ag levels were variable and showed no consistent pattern over the study period. PAI-1 Ag and PAI activity levels were significantly increased (p < 0.02-0.0005) in all four groups for the first 24 h, and individual patients showed increased levels at various times over the study period. The only significant prethrombolysis fibrinolytic change was increased PAI activity and PAI-1 Ag. The only significant effect of heparin was a shortening of the period of decreased global fibrinolysis observed in the rt-PA group from 5 to 2 days. Our findings show that the fibrinolytic shut-down after AMI in patients receiving thrombolysis is short-lived, lasting only a few days. Key Words : Thrombolysis—Myocardial infarction-Fibrinolysis-Heparin.

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