FGL1 as a modulator of plasma D‐dimer levels: exome‐wide marker analysis of plasma tPA, PAI‐1 and D‐dimer

2021 ◽  
Author(s):  
Florian Thibord ◽  
Ci Song ◽  
Jack Pattee ◽  
Benjamin A.T. Rodriguez ◽  
Ming‐Huei Chen ◽  
...  
Keyword(s):  
Marker Analysis ◽  
Pai 1 ◽  
D Dimer

One Month Follow-up of Haemostatic Variables in Patients Undergoing Aortocoronary Bypass Surgery

1995 ◽  
Vol 73 (03) ◽  
pp. 356-361 ◽  
Author(s):  
L Mannucci ◽  
P S Gerometta ◽  
L Mussoni ◽  
C Antona ◽  
A Parolari ◽  
...  
Keyword(s):  
Cardiopulmonary Bypass ◽  
Bypass Surgery ◽  
Fibrinolytic System ◽  
Aortocoronary Bypass ◽  
Protamine Sulphate ◽  
Aortocoronary Bypass Surgery ◽  
Intraoperative Period ◽  
Pai 1 ◽  
D Dimer

SummaryIt is already known that activation of the coagulation and fibrinolytic system occurs in patients undergoing cardiopulmonary bypass (CPB). We have thus studied twenty patients (10 treated with aprotinin during CPB and 10 untreated) both during the intraoperative period and during thirty days follow up. In untreated patients D-dimer levels increased 4-fold during CPB and the levels were above baseline for the whole follow up (p<0.0001). D-dimer levels were reduced in aprotinin treated patients in comparison to untreated patients (p = 0.0172); levels then gradually increased to the values of the untreated patients over the following 24 h later and remained higher during the thirty day follow up. The behavior of haemostatic variables in the 24 h after CPB did not vary between untreated and aprotinin treated patients. In particular, five minutes after protamine sulphate administration, levels of F1 + 2 and TAT rose significantly (p = 0.0054, p = 0.0022 respectively), whereas fibrinogen significantly decreased (p<0.0001) and PAI-1 antigen levels were reduced. Two days after CPB the concentrations of F1 + 2 and TAT lowered, whereas fibrinogen and PAI-1 antigen levels increased. On the 5th, 8th and 30th days after CPB, F1 + 2 and TAT levels remained higher than those reported at baseline in both groups of patients, whereas fibrinogen levels increased over basal levels in aprotinin treated patients only.Thus, in addition to the activation of the coagulation and fibrinolytic system occurring during the intraoperative period, in patients undergoing CPB, there are alterations of haemostatic variables up to thirty days from surgery.

Aktivierungs- und Umsatzmarker der Hämostase im Verlauf der akuten tiefen Beinyenenthrombose

1995 ◽  
Vol 15 (02) ◽  
pp. 87-91 ◽  
Author(s):  
Ch. Burstein ◽  
S. Bitter ◽  
M. Kundt ◽  
M. Freund ◽  
O. Anders
Keyword(s):  
Thrombolytische Therapie ◽  
Pai 1 ◽  
D Dimer

ZusammenfassungIn einer prospektiven Untersuchung wurde das Verhalten von Thrombin-Antithrombin-lll-(TAT-)Komplex, D-Dimer, Plasminogenaktivator-lnhibitor-1 (PAI-1) und weiteren Parametern der Hämostase bei 50 Patienten mit spontaner tiefer Beinvenenthrombose bei Stellung der Diagnose während der initialen Behandlung und bei der ambulanten Kontrolle untersucht: 37 Patienten erhielten eine thrombolytische Therapie, davon 31 Patienten mit Streptokinase in ultrahoher Dosierung (UHSK) und sechs Patienten mit Urokinase; 13 Patienten wurden mit einer Heparininfusion behandelt.Im Vergleich zu den Patienten mit einer Heparintherapie führte die thrombolytische Therapie zu einem Anstieg von TAT (p <0,05), D-Dimer (p <0,01) und von PAI-1 (p <0,05). Bei vier Patienten trat eine Rethrombose nach Thrombolyse auf. Nach fibrinolytischer Therapie wurde eine Aktivierung der Gerinnung und eine erhöhte Aktivität von PAI-1 nachgewiesen, die für die Entstehung einer Rethrombose von Bedeutung sein können.

Influence of insulin-induced hypoglycemia on the hemostatic and fibrinolytic system in patients with hypothalamicpituitary disorders

1998 ◽  
Vol 18 (02) ◽  
pp. 74-79
Author(s):  
K.-H. Zurborn ◽  
H. D. Bruhn ◽  
H. Mönig
Keyword(s):  
Factor Viii ◽  
Plasminogen Activator ◽  
Tolerance Test ◽  
Insulin Tolerance Test ◽  
Fibrinolytic System ◽  
Tissue Type ◽  
Insulin Tolerance ◽  
Factor Viii Antigen ◽  
Pai 1 ◽  
D Dimer

SummaryIn order to study the acute and prolonged effects of hypoglycemia on the hemostatic and fibrinolytic system we measured prothrombin fragment (F1+2), thrombin-antithrombin III complex (TAT), platelet factor 4 (PF4), β-thromboglobulin (âTG), factor VIII antigen (F VIII antigen), D-dimer, tissue-type plasminogen activator (t-PA) antigen, and plasminogen activator inhibitor (PAI-1) in 22 patients during insulin tolerance test. F1+2 and TAT increased significantly 15 and 90 minutes after administration of insulin, as did PF4 and âTG. At 4 and 24 hours, these parameters were not different from baseline. Factor VIII antigen was not significantly altered. D-dimer concentration did not change. However, the D-dimer/TAT ratio significantly decreased at 15 and 90 minutes but increased markedly above baseline at 4 and 24 hours. t-PA antigen was also found to be elevated at 15 and 90 minutes but had returned to baseline at 4 and 24 hours. PAI-1 concentration did not change. We conclude from these data that both coagulation and fibrinolysis are activated in the short-term response to acute insulin-induced hypoglycemia, followed by a prolonged activation of fibrinolysis. Our study may explain why patients undergoing insulin tolerance test, despite marked clotting and platelet activation, almost never develop thromboembolic complications.

Hemostatic Parameters and Platelet Activation Marker Expression in Cyanotic and Acyanotic Pediatric Patients Undergoing Cardiac Surgery in the Presence of Tranexamic Acid

2000 ◽  
Vol 83 (01) ◽  
pp. 54-59 ◽  
Author(s):  
Elena Levin ◽  
John Wu ◽  
John Alexander ◽  
Clayton Reichart ◽  
Suvro Sett ◽  
...  
Keyword(s):  
Cardiac Surgery ◽  
Blood Loss ◽  
Tranexamic Acid ◽  
Platelet Activation ◽  
Pediatric Patients ◽  
Factor Xiiia ◽  
Congenital Defects ◽  
Plasma Factor ◽  
Pai 1 ◽  
D Dimer

SummaryWe have investigated hemostatic parameters including platelet activation in 56 pediatric patients with or without cyanosis undergoing cardiopulmonary bypass (CPB) and cardiac surgery to repair congenital defects. Patients were participants in a study assessing the effects of tranexamic acid on surgery-related blood loss. Parameters monitored included blood loss, prothrombin F1.2, thrombin-antithrombin complexes, t-PA, PAI-1, plasminogen, fibrin D-dimer, and plasma factor XIII. Additionally, flow cytometry monitored platelet degranulation (P-selectin or CD63), as well as surface-bound fibrinogen, von Willebrand factor and factor XIIIa. Cyanotic patients had evidence of supranormal coagulation activation as both fibrin D-dimer and PAI-1 levels were elevated prior to surgery. While the extent of expression of Pselectin or CD63 was not informative, platelet-associated factor XIIIa was elevated in cyanotic patients at baseline. In both patient groups, CPB altered platelet activation state and coagulation status irrespective of the use of tranexamic acid.

PAI-1 and D-Dimer in Type 2 Diabetic Women With Asymptomatic Macrovascular Disease Assessed by Carotid Doppler

2009 ◽  
Vol 16 (2) ◽  
pp. 204-208 ◽  
Author(s):  
Anna Letícia Soares ◽  
Pedro Wesley Rosário ◽  
Michelle Aparecida Ribeiro Borges ◽  
Marinez Oliveira Sousa ◽  
Ana Paula Salles Moura Fernandes ◽  
...  
Keyword(s):  
Carotid Plaque ◽  
Macrovascular Disease ◽  
Intima Media Thickness ◽  
Plasminogen Activator Inhibitor ◽  
Diabetic Patients ◽  
Plasminogen Activator Inhibitor 1 ◽  
Type 2 Diabetic ◽  
Pai 1 ◽  
D Dimer

Asymptomatic diabetic patients with different degrees of macrovascular complications can present different hemostatic changes. At this study, plasminogen activator inhibitor-1 (PAI-1) and D-dimer were evaluated in 12 women without diabetes and 64 type 2 diabetic women. All patients were classified into 3 different categories according to the carotid intima-media thickness (IMT) assessed by Doppler: 25 with <1 mm (normal), 15 with >1 mm and without plaque (intermediate), and 24 with stenosis lower than 50% of the vessel lumen (plaque). The results showed increased plasma D-dimer in type 2 diabetic women with carotid plaque when compared to the other groups. High levels of PAI-1 were observed in all the 3 groups of diabetic women when compared to women without diabetes. Our results suggest that high levels of PAI-1 in type 2 diabetic women are only associated with diabetes and are not associated with macrovascular progression; however, it seems that D-dimer plasma levels are associated with carotid plaque.

Abstract P663: Polygenic Risk Scores for Plasma Levels of Fibrin D-Dimer and Tissue Plasminogen Activator Are Associated With Non-Lacunar Stroke

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Yonit A Addissie ◽  
Brady Gaynor ◽  
Thomas Jaworek ◽  
Huichun Xu ◽  
Colin O Stine ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Plasma Levels ◽  
Early Onset ◽  
Late Onset ◽  
Plasma Concentrations ◽  
Risk Scores ◽  
Lacunar Stroke ◽  
Related Factors ◽  
Pai 1 ◽  
D Dimer

Introduction: Plasma concentrations of prothrombotic factors such as fibrinogen have previously been associated with ischemic stroke risk. To extend this observation, we examined the association of polygenic risk scores (PRS) for increased plasma levels of thrombosis-related factors with ischemic stroke. Our hypotheses were that these PRS would be more associated with early than late onset stroke and with non-lacunar than lacunar stroke. Methods: We identified 9053 late onset (≥ 60 years) stroke cases from the NINDS International Stroke Genetics Consortium (SiGN) with 24804 controls and 6594 early onset (< 60 years) stroke cases from the Genetics of Early Onset Ischemic Stroke Consortium with 30561 controls. We identified previously known loci associated with plasma levels of four thrombosis-related factors: fibrinogen, fibrin D-dimer, tPA and PAI-1 from prior GWAS studies and developed genome-wide PRS for plasma concentrations of these factors. We then used logistic regression to test the association of these scores with risk of stroke and stroke subtype. Results: PRS for fibrin D dimer levels were associated with increased risk for all stroke and specifically for older (p = 0.019), but not younger (p = 0.22) onset stroke. PRS for tPA levels were also marginally associated with older (p = 0.06), but not younger (p = 0.24) onset stroke. Genetic risk scores for both D dimer and tPA were associated with non-lacunar stroke (Table 1). Further analyses stratified by age revealed PRS for D dimer to be significantly associated with non-lacunar stroke (but not lacunar stroke) in both late and early onset cohorts. PRS for fibrinogen and PAI-1 were not associated with stroke. Conclusion: Genomic risk scores for thrombosis-related factors including D dimer and tPA levels were associated with risk for ischemic stroke, and specifically, non-lacunar stroke.

Tissue Plasminogen Activator Plasma Levels as a Potential Diagnostic Aid in Acute Pulmonary Embolism

2003 ◽  
Vol 127 (3) ◽  
pp. 310-315
Author(s):  
Julio Flores ◽  
Angel García-Avello ◽  
Victor M. Flores ◽  
JoséL. Navarro ◽  
Felipe Canseco ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Lower Limb ◽  
Pulmonary Angiography ◽  
Enzyme Linked Immunosorbent Assay ◽  
Clinical Probability ◽  
Tissue Plasminogen ◽  
Lung Scan ◽  
Pai 1 ◽  
D Dimer

Abstract Context.—Pulmonary embolism (PE) is a potentially fatal and frequent complication of deep venous thrombosis, and the most reliable techniques for the diagnosis of PE are not universally available and have other limitations. Objective.—To determine the efficacy of 4 different fibrinolysis system parameters, namely, tissue plasminogen activator (tPA), tissue plasminogen activator inhibitor type 1 (PAI-1), plasmin-antiplasmin complexes (PAP), and D-dimer, in the diagnosis of acute PE. Setting.—A 350-bed university hospital serving an area with 280 000 inhabitants. Patients.—Sixty-six consecutive outpatients with clinically suspected PE. The diagnosis of PE was based on ventilation-perfusion (V/Q) lung scan in combination with clinical assessment, lower limb study, and (when required) pulmonary angiography. Main Outcome Measures.—At the moment of clinical suspicion, a sample of venous blood was obtained to measure levels of tPA, PAI-1, PAP, and D-dimer using an enzyme-linked immunosorbent assay method. Results.—Twenty-seven patients (41%) were classified as PE positive (high clinical probability and V/Q lung scan [n = 12], nondiagnostic V/Q lung scan and high clinical probability [n = 1], inconclusive V/Q lung scan and positive lower limb examination for deep venous thrombosis [n = 11], and positive pulmonary angiography [n = 3]), and 39 patients (59%) were classified PE negative. The sensitivity/negative predictive value for tPA, using a cutoff of 8.5 ng/mL, and PAI-1, using a cutoff of 15 ng/mL, were 100%/100% and 100%/100%, respectively. A tPA level lower than 8.5 ng/mL occurred in 13 (19.7%; all PE negative) of 66 patients with suspected PE, and PAI-1 levels were lower than 15 ng/mL in 9 (13.6%; all PE negative) of 66 patients with suspected PE. The D-dimer, using a cutoff of 500 ng/mL, showed a sensitivity and negative predictive value of 92.6% and 87.5%, respectively. Conclusions.—Our data indicate that tPA and PAI-1 levels are potentially useful in ruling out PE, although tPA seems to be the better parameter. The sensitivity levels and negative predictive values for the rapid enzyme-linked immunosorbent assay for D-dimer used in this investigation were low compared with previous studies using the same test.

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.

Is Heparin Therapy Necessary in Capd Peritonitis?

1997 ◽  
Vol 17 (5) ◽  
pp. 493-496 ◽  
Author(s):  
Canradin Nadig ◽  
Ulrich Binswanger ◽  
Arthur Van Felten
Keyword(s):  
Protein Concentration ◽  
Intraperitoneal Administration ◽  
Plasminogen Activator Inhibitor ◽  
Heparin Therapy ◽  
Plasminogen Activator Inhibitor 1 ◽  
Severe Peritonitis ◽  
Leukocyte Counts ◽  
Activator Inhibitor ◽  
Pai 1 ◽  
D Dimer

Objective Heparin therapy in continuous ambulatory peritoneal dialysis (CAPD) peritonitis seems well established; it is costly due to the necessity of hospitalization. There are no clinical studies that show a benefit of such a treatment. The aim of this study was to investigate whether heparin therapy in CAPD peritonitis isnecessary. Design and Patients 194 samples of peritoneal dialysates were collected from 17 patients over a period of 24 months. Samples were subdivided into three groups: those without peritonitis (<100 leukocytes/ILL), those with mild peritonitis (100 -499 leukocytes/ILL), and those with severe peritonitis (≥500 leukocytes/ILL). Measurements The number of leukocytes per ILL dialysate and total protein concentrations were determined. Furthermore, dialysate concentrations of thrombin-antithrombin 111 (TAT-) complexes (indicator of thrombin formation), D-dimers (indicator of fibrinolysis), and plasminogen activator inhibitor 1 (PAI-1) were measured. Results The dialysate protein concentration progressively increased from no peritonitis to mild and severe inflammation. In parallel, dialysate TAT -complex and D-dimer concentrations increased. Thrombin-antithrombin 1I1-complex and D-dimer concentrations correlated strongly in 179 cases (r = 0.76; 62 samples showing peritonitis, 117 samples with no evidence of peritonitis). In the remaining 15 samples of 3 patients, high PAI-1 levels (>40 ng/mL) and low D-dimer concentrations were found. Eleven of the 15 samples showed evidence of peritonitis. In these 11 samples with evidence of peritonitis, high levels of TAT -complexes were detected, while Ddimer concentrations were found to be very low, pointing to a blocked fibrinolysis. The P AI-1levels were not related to leukocyte counts or protein concentrations in the dialysates. Conclusions Based on our findings, the routine intraperitoneal administration of heparin in CAPD peritonitis is not necessary. In rare cases an imbalance between coagulation and fibrinolysis due to high PAI-1 levels exists (15 of 194 dialysate samples, 11 of the 15 samples showing peritonitis). These cases -which do require heparinization -can be identified by demonstrating low D-dimer levels in CAPD dialysate at times of peritonitis.

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