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.

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.

Defective Fibrinolysis in Venous Thrombosis

1981 ◽  
Vol 26 (1_suppl) ◽  
pp. S15-S19
Author(s):  
J. A. Davies ◽  
A. J. Crandon ◽  
G. P. McNicol
Keyword(s):  
Laboratory Tests ◽  
Varicose Veins ◽  
High Risk Group ◽  
Unexpected Finding ◽  
Vein Thrombosis ◽  
Lysis Time ◽  
Euglobulin Lysis Time ◽  
Clinical Measurements ◽  
Deep Vein ◽  
Low Dose Heparin

In previous studies a variety of attempts have been made to define laboratory tests which could predict patients who would develop deep vein thrombosis post-operatively. Such tests included the partial thromboplastin time, haematocrit and platelet adhesiveness. In this study patients undergoing gynaecological surgery were screened in advance with a panel of clinical measurements and laboratory tests and the development of DVT was noted using 125I-fibrinogen leg scanning. The values for the selected variables were analysed using logistic discrimination. The factors with the greatest prediction were the euglobulin lysis time, age, varicose veins, serum FR-antigen and percentage overweight for height. When this formula was applied to a further group of patients it allowed a ‘high risk’ group to be defined and these were given low-dose heparin with a significant reduction in the incidence of post-operative DVT. An unexpected finding was that patients who smoked cigarettes appeared to be protected from post-operative DVT.

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.

Systemic Fibrinolytic Activity and Inhibitor Levels During Treatment of Deep Vein Thrombosis with Urokinase and Streptokinase

1983 ◽  
Vol 50 (03) ◽  
pp. 664-668 ◽  
Author(s):  
W Theiss ◽  
F Asbeck ◽  
A Kriessmann ◽  
G Trübestein ◽  
K Knoch ◽  
...  
Keyword(s):  
Deep Vein Thrombosis ◽  
Fibrinolytic Activity ◽  
Clot Lysis ◽  
Treatment Groups ◽  
Vein Thrombosis ◽  
Lysis Time ◽  
Euglobulin Clot Lysis Time ◽  
Deep Vein ◽  
Dose Dependent ◽  
Urokinase Infusion

SummaryIn a prospective, randomized trial 33 patients with deep vein thrombosis were treated either with 2,200 or 1,100 IU/kg/h urokinase or with 100,000 IU/h streptokinase for at least 6 days. While streptokinase was given continuously, urokinase was administered intermittently (12 hr urokinase alternating with 12 hr heparin).Urokinase treatment resulted in a dose-dependent fibrinolytic state with shortening of the euglobulin clot lysis time, easily demonstrable amidolytic activity and moderate decrease of plasminogen. At the end of each urokinase-free interval the fibrinolytic activity had mostly faded, but was reproducibly elicited again by each new urokinase administration. Streptokinase immediately evoked the customary, intense fibrinolytic state, which progressively tapered off as plasminogen fell to 1% of its pretreatment concentration. In all treatment groups α-2-antiplasmin dropped to approximately 40% of its initial value during the first 12 hr with a further decrease to about 20% after 6 days, α-2-macroglo- bulin fell only moderately with either urokinase regimen, whereas it decreased progressively to 45% under streptokinase.While the fibrinolytic activity decreased under streptokinase over the 6-day infusion period, it appeared to increase with each successive urokinase infusion particularly with 1100 IU/kg/h. Thus the final euglobulin clot lysis times and the final fibrinogen concentrations were similar in all three treatment groups on the sixth day.

The incidence of activated protein C resistance among patients with deep vein thrombosis and healthy subjects in Osaka

1995 ◽  
Vol 79 (2) ◽  
pp. 227-229 ◽  
Author(s):  
J. Kambayashi ◽  
H. Fujimura ◽  
T. Kawasaki ◽  
M. Sakon ◽  
M. Monden ◽  
...  
Keyword(s):  
Deep Vein Thrombosis ◽  
Healthy Subjects ◽  
Protein C ◽  
Activated Protein C ◽  
Activated Protein C Resistance ◽  
Vein Thrombosis ◽  
Deep Vein

The Contribution Of Increased Fibrinolysis Induced By Intermittent Pneumatic Compression Of The Legs In The Prevention Of Deep Vein Thrombosis

1981 ◽  
Author(s):  
A C de Boer ◽  
A G G Turpie ◽  
R Butt ◽  
E Genton
Keyword(s):  
Deep Vein Thrombosis ◽  
Fibrinolytic Activity ◽  
Intermittent Pneumatic Compression ◽  
Venous Stasis ◽  
Clot Lysis ◽  
Vein Thrombosis ◽  
Lysis Time ◽  
Neurosurgical Patients ◽  
Antifibrinolytic Drugs ◽  
Deep Vein

Intermittent pneumatic compression (IPC) consistently prevents venous stasis by increasing venous return of the legs but fails to prevent deep vein thrombosis (DVT) in some patients, especially patients with malignancy and subarachnoid haemorrhage (SAH). This suggests a mechanism in addition to preventing stasis is required for the prophylactic effect of IPC. IPC increases fibrinolysis and this may contribute to DVT prevention. In 74 patients with SAH treated with anti fibrinolytic drugs, 21% of 42 randomized to IPC prophylaxis developed DVT and 19% of 32 controls. In 143 neurosurgical patients aged >55 years and not treated with antifibrinolytic drugs, 30% of controls (n=76) developed DVT compared to 16% treated with IPC (n=67; p>0.05), in contrast to 187 patients <55 years in whom 20% of controls (n=88) developed DVT, compared with none in the IPC group (n=99; p< 0.001). The effect of IPC on fibrinolytic activity in 80 of these patients was evaluated using a modification of the dilute blood clot lysis time (mean ± SEM, hrs). In 64 medical control patients there was a correlation between age and lysis time (r=0.33; p<0.05). In operative patients aged <55 years, lysis time was significantly shortened in patients given IPC compared with age-matched controls (6.3 + 0.6 v 8.8 + 0.8; p<0.05). In patients aged >55, there was no difference in lysis time in IPC patients compared with age-matched controls (10.2 ± 1.4 v 9.7 ± 0.8; p> 0.1). In all patients treated with antifibrinolytic drugs, lysis times were markedly prolonged. The data show that ineffectiveness of IPC in certain patient groups was related to failure of enhancement of fibrinolytic activity and this is consistent with the hypothesis that activation of fibrinolysis contributes to the prevention of DVT with IPC.

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