Resistin Promotes Thrombosis in Rats with Deep Vein Thrombosis via Up-Regulating MMP-2, MMP-9, and PAI-1

2019 ◽  
Vol 65 (10/2019) ◽  
Author(s):  
Yang Ding ◽  
Xiaoqiang Li
Keyword(s):  
Deep Vein Thrombosis ◽  
Vein Thrombosis ◽  
Deep Vein ◽  
Pai 1

Does Low Protein Concentration of Tissue-type Plasminogen Activator Predict a Low Risk of Spontaneous Deep Vein Thrombosis?

1995 ◽  
Vol 74 (02) ◽  
pp. 718-721 ◽  
Author(s):  
Jørgen Gram ◽  
Johannes Sidelmann ◽  
Jørgen Jespersen
Keyword(s):  
Deep Vein Thrombosis ◽  
Confidence Interval ◽  
Plasminogen Activator ◽  
Fibrinolytic Activity ◽  
Protein Concentration ◽  
Tissue Type ◽  
Vein Thrombosis ◽  
Low Protein ◽  
Deep Vein ◽  
Pai 1

SummaryMany reports have demonstrated an abnormal fibrinolysis in a subset of patients with deep vein thrombosis. We have studied systemic global fibrinolytic activity and protein concentrations of tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) in plasma of 25 young patients with a previous instance of spontaneous deep vein thrombosis documented by phlebography and in 50 healthy controls. The two populations were comparable with respect to a number of base-line variables (age, height, weight, etc.), while the patients had significantly lower fibrinolytic activity (p <0.02), and significantly higher protein concentrations of t-PA (p <0.0001) and PAI-1 (p <0.0006).We used probit scale plots to identify the consequence of different cut-off points to separate patients from controls. Reasonable separation could be obtained for t-PA with a cut-off point of 5.2 ng/ml and for PAI-1 18 ng/ml. The sensitivity and specificity for these cut-off points were for t-PA 73% (95% confidence interval 63%-84%) and for PAI-1 67% (confidence interval 55%-77%). The negative predictive value with a cut-off point t-PA concentration of 5.2 ng/ml was 85% (95% confidence interval 70%-94%). We observed a significantly negative association between concentration of t-PA and fibrinolytic activity (rs = -0.47; p <0.005) and also between PAI-1 and fibrinolytic activity (rs = -0.78; p <0.005).We conclude that a young healthy population is characterized by low protein concentration of t-PA (and PAI-1) compared with young patients with a previous instance of spontaneous vein thrombosis, and we tentatively state that a low protein concentration of t-PA predicts a low risk of spontaneous deep vein thrombosis.

Hypofibrinolysis in Patients with a History of Idiopathic Deep Vein Thrombosis and/or Pulmonary Embolism

1992 ◽  
Vol 67 (04) ◽  
pp. 397-401 ◽  
Author(s):  
Vito Grimaudo ◽  
Fedor Bachmann ◽  
Jacques Hauert ◽  
Maria-Adele Christe ◽  
Egbert K O Kruithof
Keyword(s):  
Pulmonary Embolism ◽  
Deep Vein Thrombosis ◽  
Plasminogen Activator ◽  
Fibrinolytic Activity ◽  
Venous Occlusion ◽  
Vein Thrombosis ◽  
Molar Excess ◽  
History Of ◽  
Deep Vein ◽  
Pai 1

SummaryAn impaired fibrinolytic activity after a venous occlusion test is the most common abnormality associated with thomboembolic disease. To better characterize the causes of abnormal responses we have measured different fibrinolytic parameters, before and after 10 and 20 min of venous occlusion, in 77 patients with a history of idiopathic deep vein thrombosis and/or pulmonary embolism and in 38 healthy volunteers.The patients had a lower mean fibrinolytic response to venous occlusion than the controls and higher antigen levels of tissue-type plasminogen activator (t-PA: Ag) and plasminogen activator inhibitor type 1 (PAI-1:Ag). Before venous occlusion, PAI-1 levels were at a molar excess over those of t-PA in all patients and controls. After 20 min of venous occlusion, the release of t-PA from the vascular endothelium resulted in a molar excess of t-PA over PAI-1 in the majority of controls (72%) but only in a minority of patients (39%).To identify patients with fibrinolytic abnormalities, reference intervals (RI) for fibrinolytic activity, t-PA:Ag and PAI-1:Ag were established in healthy controls. None of the patients had low levels of t-PA:Ag, but 17 (22%) had elevated PAI-1:Ag levels before venous occlusion and 12 (16%) exhibited low fibrinolytic activity after 20 min of venous occlusion. Ten of these were among the 17 subjects with high PAI-1: Ag levels before venous occlusion. Thus, the measurement of PAI-1:Ag levels before venous occlusion (i.e. in samples taken without any stimulation) is a sensitive (83%) and specific (89%) assay for the detection of patients with an impaired fibrinolytic response to venous occlusion.

4G/5G Polymorphism of PAI-1 Gene Promoter and Fibrinolytic Capacity in Patients with Deep Vein Thrombosis

1998 ◽  
Vol 80 (12) ◽  
pp. 956-960 ◽  
Author(s):  
Maria Teresa Sartori ◽  
Björn Wiman ◽  
Silvia Vettore ◽  
Francesco Dazzi ◽  
Antonio Girolami ◽  
...  
Keyword(s):  
Deep Vein Thrombosis ◽  
Healthy Subjects ◽  
Gene Promoter ◽  
Insertion Polymorphism ◽  
Vein Thrombosis ◽  
Lysis Time ◽  
Euglobulin Lysis Time ◽  
Deep Vein ◽  
Fibrinolytic Capacity ◽  
Pai 1

SummaryA deletion/insertion polymorphism (4G or 5G) in the promoter of the plasminogen activator inhibitor type 1 gene has been suggested to be involved in regulation of the synthesis of the inhibitor, the 4G allele being associated with enhanced gene expression. A relationship between 4G/5G polymorphism and PAI-1 levels was found in patients with cardiovascular and metabolic diseases, but not in healthy subjects. In the present work we studied the distribution of PAI-1 4G/5G geno-type and its relation to fibrinolytic capacity in 70 unrelated patients with deep vein thrombosis. Each patient was assayed before and after 20 min. Venous occlusion for euglobulin lysis time, t-PA antigen and activity, and PAI-1 antigen and activity. The prevalence of 5G homozygous carriers was significantly lower in patients than in controls (10% vs. 26%, p = 0.009). The 5G allele frequency was reduced, even though not significantly, in DVT patients compared to healthy subjects (0.40 vs. 0.51, respectively). In the patient group, the mean PAI-1 antigen and activity levels were significantly higher than among controls and related to the 4G/5G polymorphism. In patients with 4G/5G and 4G/4G genotype a significant correlation was found between PAI-1 levels and the global fibrinolytic activity as evaluated by euglobulin lysis time. The prevalence of a reduced fibrinolytic potential due to PAI-1 excess was 45.7% among DVT patients. Moreover, the prevalence of PAI-1 induced hypofibrinolysis was strongly related to PAI-1 polymorphism, since it was significantly lower in 5G homo-zygous patients (28.6%) than in both 4G/5G carriers (55.3%, p <0.001) and 4G homozygous patients (57.9%, p <0.001).In conclusion, in patients with deep vein thrombosis the 4G polymorphism of PAI-1 gene promoter may influence the expression of PAI-1 and it should be taken into consideration as a facilitating condition for pathological fibrinolysis together with other environmental and genetic factors. Whether this has any significance in regard to the pathogenesis of venous thrombosis remains to be proven.

PLASMINOGEN ACTIVATOR INHIBITOR ACTIVITY AND ANTIGEN (PAI 1), RELATIONSHIP TO FIBRINOLYTIC RESPONSE AFTER VENOUS OCCLUSION IN 48 PATIENTS WITH DEEP VEIN THROMBOSIS

1987 ◽  
Author(s):  
G Nguyen ◽  
M H Horellou ◽  
J Conard ◽  
P Van Dreden ◽  
E K O Kruithof ◽  
...  
Keyword(s):  
Deep Vein Thrombosis ◽  
Plasminogen Activator ◽  
Venous Occlusion ◽  
Venous Stasis ◽  
Activity Levels ◽  
Vein Thrombosis ◽  
Group 2 ◽  
Deep Vein ◽  
Pai 1 ◽  
Group 1

Fibrinolytic parameters were studied before and after a 10 minute venous occlusion (VO) in 48 patients with confirmed deep vein thrombosis (DVT), at least 3 months after the last thrombotic episode. Congenital antithrombin III or protein C deficiencies were ruled out in these patients. The following tests were performed : euglobulin clot lysis time (ECLT), diluted whole blood lysis times (DWBLT), tissue plasminogen activator (t-PA) antigen (Biopool kit) and activity (fibrin plates), PAI activity (Verheijen et al.) and PAI i antigen (RIA, Kruithof et al.).Patients were divided in 2 groups : group 1 (27 patients) with normal fibrinolytic response (ECLT and DWBLT less than 90 min. after VO), group 2 (21 patients) with defective fibrinolytic response at least twice with a few weeks time interval. In group 1, the mean t-PA antigen release after VO was 32.0 ± 27.2 ng/ml (post-occlusion value minus preocclusion value) and was associated with low or normal levels of basal PAI activity (7.1 ±3.1 IU/ml), and PAI 1 antigen (15.1 ±4.1 ng/ml, n = 7). These results could explain the good response to VO, and a PAI activity suppression after stasis (PAI activity undetectable in 20 out of 27 patients).In contrast, in group 2, a low t-PA Ag increase after VO:10.5 ± 8.2 ng/ml as compared to group 1 (p <0.001) was associated with high levels of basal PAI activity : 22.4 ± 15.4 IU/ml (p <0.001), and PAI 1 Ag : 43.6 ± 24.9 ng/ml (n = 11, p <0.001). This association may account for the impaired fibrinolytic response aftep V0, and for persistant high PAI activity levels after stasis (17.6 ± 22.5 IU/ml). Before V0, PAI 1 Ag levels were in good correlation with PAI activity (r = 0.66, p <0.01), and , were significantly higher in group 2 as compared to group 1 (only 3 patients belonging to group 2 had normal PAI levels).Since elevated PAI 1 antigen and PAI activity levels were associated with an abnormal fibrinolytic response to venous stasis, VO test could be restricted to patients with normal PAI levels, in order to detect hypofibrinolysis related to insufficient t-PA release.

Feasibility Study of Catheter-directed Thrombolysis with Recombinant Staphylokinase in Deep Venous Thrombosis

1998 ◽  
Vol 79 (03) ◽  
pp. 517-519 ◽  
Author(s):  
Stephane Heymans ◽  
Raymond Verhaeghe ◽  
Luc Stockx ◽  
Désiré Collen
Keyword(s):  
Deep Vein Thrombosis ◽  
Continuous Infusion ◽  
High Speed ◽  
Minor Bleeding ◽  
Vein Thrombosis ◽  
Catheter Directed Thrombolysis ◽  
Long Term Follow Up ◽  
Valve Function ◽  
Rotating Impeller ◽  
Deep Vein

SummaryThe feasibility of catheter-directed thrombolysis with recombinant staphylokinase was evaluated in six selected patients with deep vein thrombosis. The patients underwent intrathrombus infusion of recombinant staphylokinase (2 mg bolus followed by a continuous infusion of 1 mg/h). Heparin was given via the catheter as a bolus (5000 U) and as a continuous infusion (1000 U/h). Complete lyis was obtained in five patients and partial lysis in one patient. Complications consisted of minor bleeding in four subjects. Symptomatic reocclusion occurred in one. Debulking of the thrombus mass by a high speed rotating impeller (n = 1) and stenting (n = 3) were used as additional interventions. An underlying anatomical abnormality was present in two patients. Long term follow up revealed normal patency in all patients and normal valve function in four patients. Symptomatic venous insufficiency with valve dysfunction was present in the two with a second thrombotic episode.Thus catheter-directed infusion of recombinant staphylokinase in patients with deep vein thrombosis appears feasible and may be associated with a high frequency of thrombolysis. Larger studies to define the clinical benefit of this treatment appear to be warranted.

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