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.

Deep Vein Thrombosis and Fibrinolysis

1991 ◽  
Vol 66 (04) ◽  
pp. 426-429 ◽  
Author(s):  
Marcel Levi ◽  
Anthonie W A Lensing ◽  
Harry R Büller ◽  
Paolo Prandoni ◽  
Gerard Dooijewaard ◽  
...  
Keyword(s):  
Deep Vein Thrombosis ◽  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Tissue Type ◽  
Controlled Study ◽  
First Episode ◽  
Control Group ◽  
Vein Thrombosis ◽  
Type Plasminogen Activator ◽  
Deep Vein

SummaryIn the present study 57 consecutive patients with a first episode of venographically proven deep vein thrombosis were investigated to evaluate the release of tissue-type plasminogen activator (t-PA) and of urokinase-type plasminogen activator (u-PA) in response to DDAVP stimulation as well as the resting plasminogen activator inhibitor (PAI) concentration, comparing this to the results obtained in 66 similar patients with a clinical suspicion of thrombosis but with a normal venogram. All assays were performed without knowledge of the patient's status.Four patients in the deep vein thrombosis-group (7%) had an absent u-PA antigen response upon DDAVP infusion, while a normal response was observed in all control subjects. Patients and controls showed similar increases in t-PA antigen level upon DDAVP. High resting PAI antigen levels were encountered in 5 patients in the deep vein thrombosis-group (9%) and in 6 subjects in the control group (9%).The results from this controlled study indicate that a defective release of u-PA may occur in patients with deep vein thrombosis and may have pathogenetic significance. Furthermore it is concluded that elevation of PAI levels cannot be considered as a specific risk factor for venous thrombosis.

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.

Deficient t-PA Release and Elevated PA Inhibitor Levels in Patients with Spontaneous or Recurrent Deep Venous Thrombosis

1987 ◽  
Vol 57 (01) ◽  
pp. 067-072 ◽  
Author(s):  
I Juhan-Vague ◽  
J Valadier ◽  
M C Alessi ◽  
M F Aillaud ◽  
J Ansaldi ◽  
...  
Keyword(s):  
Deep Vein Thrombosis ◽  
Venous Thrombosis ◽  
Plasminogen Activator ◽  
Venous Occlusion ◽  
Tissue Type ◽  
Poor Responders ◽  
Inhibitor Activity ◽  
Vein Thrombosis ◽  
Recurrent Venous Thrombosis ◽  
Deep Vein

SummaryThe fibrinolytic system was investigated in 120 patients with spontaneous or recurrent deep vein thrombosis (DVT) without any known organic disease able to explain by itself the occurrence of a thrombosis and without any known defect of antithrombin III, Heparin Cofactor II, Protein C, or Protein S. The assays included: Euglobulin fibrinolytic activity (EFA), tissue-type plasminogen activator related antigen (t-PA-Ag) and plasminogen activator inhibitor activity (PA inhibitor), which were measured before and after 10 min of venous occlusion (V. O.). On the basis of the results, the patients could be classified in 3 groups:good responders with an at least two-fold increase of EFA after venous occlusion (n = 76), poor responders with a lesser increase of EFA due to deficient release of t-PA (n = 12), and poor responders with a normal t-PA release but an increased level of PA-Inhibitor (n = 32).The poor responders due to deficient t-PA release (10% of total) had a higher incidence of recurrence of deep vein thrombosis, than the other groups (p <0.01). An overall correlation was found between the level of PA-Inhibitor activity and the triglyceride level (r = 0.40, p <0.01), suggesting that these elevations may be due to a common cause, at least in some of the patients.It is concluded that a poor fibrinolytic response to venous occlusion occurs in 35 percent of DVT patients. Poor responders however fall into two categories, one fourth with deficient t-PA release who have a high risk for recurrent venous thrombosis, and three fourth with increased PA-Inhibitor levels which may be associated with underlying diseases also causing hypertriglyceridemia. Further elucidation of the correlation between recurrent venous thrombosis and deficient fibrinolysis is expected to result in more specific and adequate treatment and prevention of DVT.

Sex Differences in the Determinants of Fibrinolytic Activity

1998 ◽  
Vol 79 (03) ◽  
pp. 587-590 ◽  
Author(s):  
J. A. Cooper ◽  
D. J. Howarth ◽  
T. W. Meade ◽  
G. J. Miller ◽  
P. K. MacCallum
Keyword(s):  
Plasminogen Activator ◽  
Whole Blood ◽  
Fibrinolytic Activity ◽  
Plasminogen Activator Inhibitor ◽  
Tissue Type ◽  
Clot Lysis ◽  
Significant Difference ◽  
Main Determinants ◽  
Activator Inhibitor Type ◽  
Pai 1

SummaryImpaired whole blood fibrinolytic activity (FA), measured by the dilute clot lysis time (DCLT), is associated with first episodes of ischaemic heart disease (IHD) in the Northwick Park Heart Study in men, especially under 55 years, and in women. In a community-based study to investigate possible determinants of the DCLT, and therefore to assess which fibrinolytic components might be predictors of first IHD events, we measured fibrinolytic variables in a sub-sample of 150 healthy adults (73 males, 77 females) randomly selected from a single general practice.Most of the variance in DCLT (68% in men, 63% in women) was explained by tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor type-1 (PAI-1) activities. In multiple regression analysis there was a significant difference in the strength of the association of t-PA activity with DCLT in men compared to women (test for interaction p = 0.05), the association of t-PA activity with DCLT being significant in males but not in females. Plasma PAI-1 activity was strongly associated with DCLT in both sexes. There was no independent association of DCLT with plasma fibrinogen, t-PA antigen, other fibrinolytic inhibitors, body mass index, serum lipids or C-reactive protein.Plasma PAI-1 activity in females and both t-PA and PAI-1 activities in males are the main determinants of whole blood FA measured by DCLT. It is therefore likely that these modulators of the plasma fibrinolytic system are associated with the onset of first clinical episodes of IHD. Elevated levels of t-PA antigen were positively associated with DCLT after adjustment for age and sex and therefore indicate impaired rather than enhanced FA. Further studies of the association of FA with risk of IHD should include not only “global” measures but also assessment of t-PA and PAI-1 activities, particularly as our results suggest that their associations with IHD may differ in men and women.

The Role of Stanozolol in the Treatment of the Postphlebitic Syndrome

1981 ◽  
Vol 26 (1_suppl) ◽  
pp. S81-S83 ◽  
Author(s):  
P. E. Jarrett
Keyword(s):  
Deep Vein Thrombosis ◽  
Side Effects ◽  
Fibrinolytic Activity ◽  
Double Blind ◽  
Vein Thrombosis ◽  
Postphlebitic Syndrome ◽  
Deep Vein ◽  
Blind Crossover Study ◽  
Double Blind Crossover Study

The postphlebitic syndrome is a result of previous deep vein thrombosis and presents with oedema, pain, induration, pigmentation and ulceration. Extravascular deposition of fibrin is associated with reduced fibrinolytic activity in these patients. In a double-blind crossover study there was evidence of benefit from stanozolol which enhanced fibrinolytic activity. No side effects of any consequence were noted with a dosage of 5 mg twice per day.

Quantitative Measurement of Plasminogen Activator in Soleal Veins

1986 ◽  
Vol 1 (2) ◽  
pp. 119-123
Author(s):  
Linda de Cossart
Keyword(s):  
Deep Vein Thrombosis ◽  
Plasminogen Activator ◽  
Lower Limb ◽  
Quantitative Measurement ◽  
Rest Pain ◽  
Vein Thrombosis ◽  
Long Saphenous Vein ◽  
Wilcoxon Rank Sum Test ◽  
Low Levels ◽  
Deep Vein

Deep vein thrombosis (DVT) in the lower limb has been associated with a low level of circulating plasminogen activator (pa) and low levels of pa in the superficial hand veins of affected patients. Little is known of the pa level in the veins commonly affected by DVT. Immediately after amputation of limbs for rest pain samples of soleal veins ( n = 9) and long saphenous vein (LSV) ( n = 9) were obtained and frozen in liquid nitrogen. Six normal veins from the groins of patients having hernia repairs were taken as controls. The median activity in the soleal veins was 6796 (range 2232 to 21 570), significantly different from the LSV 1675 range (777-119) P= >0.01, Wilcoxon Rank Sum Test. The normal vein activity median was 11 221 (range 7717 to 13 410). The level of pa in the soleal veins was considerably higher than might be expected in the veins most commonly affected by DVT.

Sign in / Sign up

Export Citation Format

Share Document