The Inhibitory Effect of Aspirin on Fibrinolysis Is Reversed by Iloprost, a Prostacyclin Analogue

1989 ◽  
Vol 61 (02) ◽  
pp. 286-288 ◽  
Author(s):  
V Bertelé ◽  
L Mussoni ◽  
G Pintucci ◽  
G del Rosso ◽  
G Romano ◽  
...  
Keyword(s):  
Fibrinolytic Activity ◽  
Specific Inhibitor ◽  
Venous Occlusion ◽  
Inhibitory Effect ◽  
Venous Stasis ◽  
Prostacyclin Analogue ◽  
Fibrin Plate ◽  
Before And After ◽  
Prostacyclin Production ◽  
Pai 1

SummaryThe reduced fibrinolytic response after aspirin intake may be due to prevention of prostacyclin production. The effect of iloprost (a stable prostacyclin analogue) was tested on the fibrinolytic activity (euglobulin lysis area on fibrin plate [E.L.A.], t-PA antigen, PAI activity and PAI-1 antigen) of plasma drawn after venous stasis test from six healthy male volunteers, who each received all the following treatments according to a single-blind randomized cross-over design: placebo, iloprost, aspirin + placebo, aspirin + iloprost. The mean E. L. A. value after venous occlusion was significantly higher than the basal level after every treatment, but aspirin. Within each treatment group the t-PA antigen levels in response to venous stasis were significantly higher than the basal ones. PAI-1 antigen levels did not change significantly before and after venous stasis either within or among the treatment groups. These data are consistent with the hypothesis that the mechanism related to aspirin’s effect on fibrinolysis is mediated by suppression of vessel wall prostacyclin production. Aspirin’s inhibitory effect on fibrinolysis was in fact prevented by replacing endogenous prostacyclin with iloprost. Iloprost enhances fibrinolytic activity reduced by aspirin, but not by promoting t-PA release or by inhibiting release of the specific inhibitor, PAI-1.

Fibrinolysis in Normal Subjects - Comparison Between Plasminogen Activator Inhibitor and Other Components of the Fibrinolytic System

1988 ◽  
Vol 59 (02) ◽  
pp. 299-303 ◽  
Author(s):  
Grazia Nicoloso ◽  
Jacques Hauert ◽  
Egbert K O Kruithof ◽  
Guy Van Melle ◽  
Fedor Bachmann
Keyword(s):  
Plasminogen Activator ◽  
Fibrinolytic Activity ◽  
Plasminogen Activator Inhibitor ◽  
Venous Occlusion ◽  
Venous Stasis ◽  
Plasminogen Activator Inhibitor 1 ◽  
Plate Assay ◽  
Fibrin Plate ◽  
Activator Inhibitor ◽  
Pai 1

SummaryWe analyzed fibrinolytic parameters in 20 healthy men and 20 healthy women, aged from 25 to 59, before and after 10 and 20 min venous occlusion. The 10 min post-occlusion fibrinolytic activity measured directly in diluted unfractionated plasma by a highly sensitive 125I-fibrin plate assay correlated well with the activity of euglobulins determined by the classical fibrin plate assay (r = 0.729), but pre-stasis activities determined with these two methods did not correlate (r = 0.084). The enhancement of fibrinolytic activity after venous occlusion was mainly due to an increase of t-PA in the occluded vessels (4-fold increase t-PA antigen after 10 min and 8-fold after 20 min venous occlusion). Plasminogen activator inhibitor (PAI) activity and plasminogen activator inhibitor 1 (PAI-1)1 antigen levels at rest showed considerable dispersion ranging from 1.9 to 12.4 U/ml, respectively 6.9 to 77 ng/ml. A significant increase of PAI-1 antigen levels was observed after 10 and 20 min venous occlusion. At rest no correlation was found between PAI activity or PAI-1 antigen levels and the fibrinolytic activity measured by 125I-FPA. However, a high level of PAI-1 at rest was associated with a high prestasis antigen level of t-PA and a low fibrinolytic response after 10 min of venous stasis. Since the fibrinolytic response inversely correlated with PAI activity at rest, we conclude that its degree depends mainly on the presence of free PAI.

Changes in Clotting and Fibrinolytic Parameters Produced by Venous Stasis

1996 ◽  
Vol 2 (1) ◽  
pp. 64-68
Author(s):  
Raul Altman ◽  
Alejandra Scazziota ◽  
Jorge Rouvier
Keyword(s):  
Sodium Citrate ◽  
Vascular Endothelial Cells ◽  
Protein S ◽  
Venous Occlusion ◽  
Venous Stasis ◽  
Clot Lysis ◽  
Before And After ◽  
Fibrinolytic Parameters ◽  
Pai 1

Vascular endothelial cells have thrombosis- prevention properties through the release of some fibri nolytic factors. This capacity of endothelium was studied using the venous occlusion test (VOT) and measuring proteins released during stasis. Blood samples were col lected before and after 10 and 20 min VOT in tubes con taining sodium citrate at pH 7.0 or 4.3. A significant shortening of the euglobulin clot lysis time (ECLT) was obtained 10 and 20 min after VOT in plasma collected in citrate pH 7.0 or 4.3. No statistical difference was noted between results obtained 10 and 20 minutes after VOT. The shortening was related to the increase of tissue plas minogen activator (t-PA) released during VOT. No differ ence was detected in the concentration of tissue plasmin ogen activator inhibitor 1 (PAI-1), but PAI-1 activity mea sured in plasma from blood collected in citrate pH 7.0 decreased progressively from 10.8 ± 9.2 arbitrary units (AU)/ml to 3.76 ± 4.5 AU/ml and 0.8 ± 1.02 AU/ml (p < 0.001) after 10 and 20 min, respectively, of stasis. When the PAI-1 activity was determined in blood collected in citrate pH 4.3 for preventing in vitro complexing of PAI-1 and t-PA, results were different: PAI-1 activity decreased from a basal value of 29.2 ± 15.3 AU/ml to 24.9 ± 12.2 ( p = NS) and 18.7 ± 11.5; p < 0.02) 10 and 20 min after VOT. As result of fibrinolytic activation, other factors were modified: increase of plasminogen activators, de crease of plasminogen, and increase of D-dimer. Fibrin ogen, fibronectin, protein C, protein S, von Willebrand factor, and tissue factor pathway inhibitor concentration remained unchanged after VOT. According to our find ings, VOT can be performed with a stasis of 10 min. Good responders are related to the endothelial capacity for re leasing t-PA and urokinase-type PA (u-PA) and defined as those with an ECLT of <60 min after 10 min VOT when blood was collected in sodium citrate pH 7.0.

Defective Fibrinolytic Response in Atherosclerotic Patients – Effect of lloprost and Its Possible Mechanism of Action

1988 ◽  
Vol 60 (02) ◽  
pp. 141-144 ◽  
Author(s):  
Vittorio Bertelé ◽  
Luciana Mussoni ◽  
Gianfranco del Rosso ◽  
Giuseppe Pintucci ◽  
Maria Rita Carriero ◽  
...  
Keyword(s):  
Fibrinolytic Activity ◽  
Arterial Disease ◽  
Venous Occlusion ◽  
Inhibitory Effect ◽  
Tissue Type ◽  
Venous Stasis ◽  
Synthetic Analogue ◽  
Type Plasminogen Activator ◽  
Parallel Increase ◽  
Artery Disease

SummaryPlasma fibrinolytic activity and tissue-type plasminogen activator (t-PA) were defective in response to venous stasis in five out of ten patients with peripheral occlusive artery disease. Discontinuous infusions of iloprost, a stable synthetic analogue of prostacyclin, restored a normal fibrinolytic response in all five patients but did not induce a parallel increase of plasma t-PA. These findings suggest that in addition to the possible benefits due to its vasodilatory and antiplatelet activity, iloprost may improve the fibrinolytic activity in patients with atherosclerotic disease, providing them with further antithrombotic protection. The profibrinolytic effect of iloprost seems not to depend on its ability to induce vascular t-PA release. Rather, it might be related to its inhibitory effect on PAI release from platelets, endothelial cells and/or hepatocytes. Venous occlusion test represents an easy diagnostic approach to fibrinolytic defects, even if related to arterial disease, and may help select patients who need therapeutic intervention.

Release Pattern of the Vascular Plasminogen Activator and Its Inbibitor in Human Postvenous Occlusion Plasma as Assessed by a Spectrophotometric Solid-Phase Fibrin-tPA Activity Assay

1987 ◽  
Vol 58 (03) ◽  
pp. 843-849 ◽  
Author(s):  
E Anglés-Cano ◽  
B Boutière ◽  
D Arnoux ◽  
C Masson ◽  
G Contant ◽  
...  
Keyword(s):  
Healthy Subjects ◽  
Solid Phase ◽  
Specific Inhibitor ◽  
Venous Occlusion ◽  
Inhibitory Effect ◽  
Fibrinolytic Enzyme ◽  
Tissue Type ◽  
Activity Assay ◽  
High Affinity ◽  
Before And After

SummaryVascular or tissue-type plasminogen activatbr(plasma t-PA) is the circulating physiological fibrinolytic enzyme of endothelial cell origin which function is regulated by fibrin and a specific inhibitor (PAI). To study the pattern of release of t-PA and the behavior of t-PA-PAI complexes in plasma. we determined t-PA activity in 44 healthy subjects before and after 10 min offorearm venous occlusion using a new spectrophotmnetrio solid-phase fibrin-tPA activity assay. The assay is based on 1) the high affinity binding of t-PA tofibrin, and 2) the detection of fibrin-bound t-PA by measuring the release of pNA from a chromogenic substrate in the presence of plasminogeu. Values at.rest were rather undetectable in plasma (0.05 ± 0.03 IU/ml, in 23 out of 44 samples) but were positively detected in all the euglobulins: 0.88 ± 0.68 IU/ml. After venous occlusion the majority ofplasmas (36 out of 44) shoWed a slight increase in t-PA activity (0.65 ± 0.63 IU/ml) as compared to the important level observed in all the euglobulins (9.78 ± 9.58 IU/ml). So, the ratio plasma/euglobulin t-PA activity was very low (0.06) and remained identical in both pre- and postocclusion samples. However, when diluted plasmas were tested the inhibitory effect disappeared and t-PA activity increased indicating that although t-PA circulates in a neutralized state it can be available for fibrinolysis. Since 1) no binding of α2 antiplasmin to fibrin in solid-phase could be demonstrated, 2) there was no correlation between α2 antiplasmin and t-PA activity, and 3) a PAI-depleted plasma with a normal content of α2 antiplasmin did not suppress the activity of t-PA, the inhibitory effect was attributed to PAL Our findings suggest that both t-PA and PAI are released. by venous occlusion and circulates in plasma as a t-PA-PAI complex.

Impaired Fibrinolytic Response To DDAVP And Venous Occlusion In A Subgroup Of Patients With Von Willebrand’s Disease

1981 ◽  
Author(s):  
H Niessner ◽  
Ch Korninger ◽  
K Lechner
Keyword(s):  
Fibrinolytic Activity ◽  
Hemophilia A ◽  
Fold Increase ◽  
Venous Occlusion ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease ◽  
Fibrin Plate ◽  
Before And After ◽  
Euglobulin Lysis Time ◽  
Von Willebrand

Fibrinolytic activity (Euglobulin lysis time, fibrin plate method) and factor VIII related properties (VIII :C , VIIIR : Ag , VIIIR : RCF) were determined in 8 healthy controls,in 21 patients with mild hemophilia A and in 15 patients with von Willebrand’s disease (vWD) before and after infusion of 0,4 μg/kg b.w. DDAVP(I-desamino-8-D-arginin vasopressin).Following infusion of DDAVP a marked increase of fibrinolytic activity occured in all controls and all patients with mild hemophilia A. However, in 7 out of 15 patients with vWD activation of fibrinolysis was absent or slight only. In these 7patients venous occlusion also did not induce activation of fibrinolysis. Activation of fibrinolysis was absent in all 5 patients with severe vWD (VIIIR:RCF < 3%) and DDAVP also did not raise the VIIIR:RCF level. In the mild cases of vWD fibrinolytic activation after DDAVP was impaired only in 2 out of 10 patients. In these mild cases an about 2 fold increase of VIIIR:RCF after DDAVP was equally observed in fibrinolytic “responders” and “non-responders”. The results indicate a combined endothelial cell defect in a subgroup of patients with vWD,resulting in impaired production/release of von Willebrand factor and impaired production/release of vascular fibrinolytic activator.

A Plasma Clot Lysis Assay Based on the Release of Fibrin Degradation Products: Application to the Diagnosis of Hypofibrinolytic States

1990 ◽  
Vol 63 (01) ◽  
pp. 076-081 ◽  
Author(s):  
Pascale Gaussem ◽  
Sophie Gandrille ◽  
Pascale Molho-Sabatier ◽  
Loïc Capron ◽  
Jean-Noël Fiessinger ◽  
...  
Keyword(s):  
Degradation Products ◽  
Venous Occlusion ◽  
Lower Limbs ◽  
Clot Lysis ◽  
Plasma Clot ◽  
Vein Thrombosis ◽  
Fibrin Degradation Products ◽  
Before And After ◽  
Euglobulin Clot Lysis Time ◽  
Pai 1

SummaryUsing a monoclonal antibody-based assay, we measured the fibrin degradation product release in the supernatant of plasma clots obtained before and after venous occlusion (VO) in 30 patients with definite or suspected vascular thrombosis (19 definite and 2 suspected deep vein thrombosis, 6 recurrent superficial thrombophlebitis, 3 arterial occlusions of lower limbs). tPA and PAI-1 concentrations were determined using ELISA assays; the post-occlusion values were corrected for haemoconcentration. The increase in tPA during VO was correlated with haemoconcentration (r = 0.74), but 3 patients had ineffective VO (<2% increase in proteins). The fibrinolytic response to VO was evaluated using the shortening of the time necessary for the release of 200 μg of fibrin degradation products per mg of fibrinogen (Δ T 200). Two among the 27 patients with effective VO were bad responders with a Δ T 200 <3 h (whereas all the others had Δ T 200 >10 h). These patients had respectively a deficient tPA release (Δ tPA = 1 ng/ml) and an elevated PAI-1 level at rest (33 ng/ml). Several other patients were bad responders in terms of tPA release or of shortening of the euglobulin clot lysis time but they had a normal Δ T 200. This plasma clot test reflects the ability of free tPA to bind to fibrin (the amount of which depends on the level of tPA and PAI-1), and may be useful in the diagnosis of a hypofibrinolytic state.

Fibrinolytic activity before and after venous occlusion in thrombotic cases

1990 ◽  
Vol 4 ◽  
pp. 61
Author(s):  
J. Zamboulakis ◽  
C. Tsoukala ◽  
S. Liapi ◽  
T. Mandalaki
Keyword(s):  
Fibrinolytic Activity ◽  
Venous Occlusion ◽  
Before And After

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.

Prostacyclin: Production by Vascular Endothelium and Effects on Platelet Aggregation

1979 ◽  
Author(s):  
S. Moncada ◽  
S. Bunting
Keyword(s):  
Endothelial Cells ◽  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Vascular Endothelium ◽  
Vascular Endothelial Cells ◽  
Specific Inhibitor ◽  
Inhibitory Effect ◽  
Vascular Endothelial ◽  
Prostacyclin Production

The inhibitory effect of vascular endothelial cells on platelet aggregation is due to their ability to release prostacyclin. The existence of an ADPase has been confirmed in endothelial cells but this enzymes does not seem to be related to the anti-aggregating properties of vascular endothelium. In vitro, the release of prostacyclin by humand and rabbit endothelial cells persists after several subcultures. The production of PGI2 can be demonstrated by its inhibition by aspirin-like drugs or 15-hydroperoxy arachidonic acid (a specific inhibitor of PGI2 synthesis). Moreover, the antiaggregating activity is antagonised by an antibody to 5,6 dihydro prostacyclin which cross reacts and neutralises prostacyclin.

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