Dextransulfate (DS) stimulated fibrinolytic activity in relation to the activity of tissue plasminogen activator (t-pa) and single and two chain urinary type plasminogen activator [(sc + tc) u-PA]

SummaryCoagulation and fibrinolytic activities were studied in 18 subjects with Behçet's disease and compared with results from 14 matched control patients suffering from sero-negative arthritis. Significantly higher plasma concentrations (median and range) were found in Behçet's patients for the following variables: fibrinogen 3.7 (1.7-6.9) vs 3.0 (2.0-5.1) g/1, p <0.05; von Willebrand factor antigen, 115 (72-344) vs 74 (60-119)%, p <0.002; plasminogen activator activity (106/ECLT2) 219 (94-329) vs 137 (78-197) units, p <0.002; tissue plasminogen activator inhibitor (t-PA-I) activity, 9.1 (5.5-19.3) vs 5.1 (1.8-12.0) IU/ml, p <0.002; and PAI-1 antigen, 13.9 (4.5-20.9) vs 6.4 (2.4-11.1) ng/ml, p <0.002. Protein C antigen was significantly lower: 97 (70-183) vs 126 (96-220)%, p <0.02. No differences were observed in antithrombin III activity or antigen, factor VIII coagulant activity, fibrinopeptides A and Bβ15-42, plasminogen, α-2-antiplasmin, functional and immunological tissue-plasminogen activator, thrombin-antithrombin complexes and D-dimer. Levels of tissue plasminogen activator inhibitor (activity and antigen) correlated with disease activity while fibrinogen and von Willebrand factor concentrations did not. Seven of the 18 subjects with Behçet's disease had suffered thrombotic events but it was not possible to distinguish these from the 11 patients without thrombosis using the assays performed. The results suggest the abnormal fibrinolytic activity in Behçet's disease is due to increased inhibition of tissue plasminogen activator. No abnormality of coagulation or fibrinolytic activity specific to Behçet's disease was detected.

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Binding of Tissue Plasminogen Activator to Vascular Grafts

Thrombosis and Haemostasis ◽

10.1055/s-0038-1646541 ◽

1989 ◽

Vol 61 (01) ◽

pp. 131-136 ◽

Cited By ~ 8

Author(s):

Richard A Harvey ◽

Hugh C Kim ◽

Jonathan Pincus ◽

Stanley Z Trooskin ◽

Josiah N Wilcox ◽

...

Keyword(s):

Plasminogen Activator ◽

Tissue Plasminogen Activator ◽

Fibrinolytic Activity ◽

Polymer Surface ◽

Enzymic Activity ◽

Vascular Prostheses ◽

Chemically Modified ◽

Insoluble Surfactant ◽

Tissue Plasminogen

SummaryTissue plasminogen activator labeled with radioactive iodine (125I-tPA) was immobilized on vascular prostheses chemically modified with a thin coating of water-insoluble surfactant, tridodecylmethylammonium chloride (TDM AC). Surfactant- treated Dacron, polytetrafluoroethylene (PTFE), silastic, polyethylene and polyurethane bound appreciable amounts of 125I- tPA (5-30 μg 125I-tPA/cm2). Upon exposure to human plasma, the amount of 125I-tPA bound to the surface shows an initial drop during the first hour of incubation, followed by a slower, roughly exponential release with a t½ of appoximately 75 hours. Prostheses containing bound tPA show fibrinolytic activity as measured both by lysis of clots formed in vitro, and by hydrolysis of a synthetic polypeptide substrate. Prior to incubation in plasma, tPA bound to a polymer surface has an enzymic activity similar, if not identical to that of the native enzyme in buffered solution. However, exposure to plasma causes a decrease in the fibrinolytic activity of both bound tPA and enzyme released from the surface of the polymer. These data demonstrate that surfactant-treated prostheses can bind tPA, and that these chemically modified devices can act as a slow-release drug delivery system with the potential for reducing prosthesis-induced thromboembolism.

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Tissue Plasminogen Activator Release in Chronic Venous Hypertension due to Heart Failure

Thrombosis and Haemostasis ◽

10.1055/s-0038-1656373 ◽

1992 ◽

Vol 68 (03) ◽

pp. 321-324 ◽

Cited By ~ 3

Author(s):

Irena Keber ◽

Dušan Keber ◽

Mojca Stegnar ◽

Nina Vene

Keyword(s):

Heart Failure ◽

Plasminogen Activator ◽

Tissue Plasminogen Activator ◽

Fibrinolytic Activity ◽

Venous Pressure ◽

Venous Hypertension ◽

Plasminogen Activator Inhibitor 1 ◽

Control Subjects ◽

Tissue Plasminogen ◽

Pai 1

SummaryIn order to study the effects of chronic venous hypertension due to heart failure on blood fibrinolytic activity, tissue plasminogen activator (t-PA) antigen, plasminogen activator inhibitor 1 (PAI-1) antigen, t-PA activity and PAI activity were measured before and after venous occlusion of the arm for 20 min in 15 patients with right-sided heart failure, 15 patients with left-sided heart failure, and 30 control healthy subjects. Central venous pressure, measured by observing the jugular veins, was above 15 cm of the blood column in all patients with right-sided heart failure, and normal (below 8 cm) in all patients with left-sided heart failure and control subjects. There was no difference in the basal concentrations of t-PA (11.0, 10.2 and 10.8 ng/ml; all values medians) and PAI-1 antigens and their activities between right and left-sided heart failure and the control subjects. After the occlusion, t-PA antigen increased significantly less in right-sided heart failure (28.6 ng/ml) than in left-sided heart failure and the control subjects (54.5 and 45.9 ng/ml, respectively). It was concluded that the poor increase in fibrinolytic activity that had already been reported in patients with heart failure, was due to low t-PA release during occlusion and not to a high basal PAI level. It was limited to the patients with right-sided heart failure and was probably the consequence of chronic systemic venous hypertension.

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Bioavailability in Rats of Human Recombinant Tissue Plasminogen Activator After Subcutaneous and Intramuscular Injection

Thrombosis and Haemostasis ◽

10.1055/s-0038-1661671 ◽

1986 ◽

Vol 56 (03) ◽

pp. 299-301 ◽

Cited By ~ 5

Author(s):

L J Garcia Frade ◽

S Poole ◽

S Hanley ◽

L J Creighton ◽

A D Curtis ◽

...

Keyword(s):

Plasminogen Activator ◽

Tissue Plasminogen Activator ◽

Fibrinolytic Activity ◽

Inferior Vena ◽

Peak Plasma ◽

Plasma Concentrations ◽

Vena Cava ◽

Recombinant Tissue Plasminogen Activator ◽

Fibrin Plate ◽

Tissue Plasminogen

SummaryThe bioavailability of human recombinant tissue plasminogen activator (rt-PA) in rats was measured after subcutaneous (s.c.) and intramuscular (i.m.) injection. Rt-PA was absorbed after both i.m. and s.c. injection, giving peak plasma concentrations within 30 min and 1 h, respectively, with detectable concentrations up to 6 h. These peak values of bioavailable t-PA were obtained in a functional fibrin plate assay of euglobulin precipitates and expressed as +88% and +243% (for s.c. and i.m. routes respectively) above basal rat fibrinolytic activity. Prior injection of rt-PA, s.c. or i.m., significantly reduced the weights of thrombi induced in the inferior vena cava after injection.

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An Enzyme Linked Immunosorbent Assay for Determination of Tissue Plasminogen Activator Applied to Patients with Thromboembolic Disease

Thrombosis and Haemostasis ◽

10.1055/s-0038-1665299 ◽

1983 ◽

Vol 50 (03) ◽

pp. 740-744 ◽

Cited By ~ 139

Author(s):

Nils Bergsdorf ◽

Torbjörn Nilsson ◽

Per Wallén

Keyword(s):

Plasminogen Activator ◽

Tissue Plasminogen Activator ◽

Specific Activity ◽

Thromboembolic Disease ◽

Tissue Type ◽

Enzyme Linked Immunosorbent Assay ◽

Type Plasminogen Activator ◽

Tissue Plasminogen ◽

Normal Human

SummaryUtilizing the immunoglobulin fraction from a goat antiserum against human uterine tissue plasminogen activator, an enzyme- linked immunoassay for tissue-type plasminogen activator in human plasma has been developed. With the new method, the concentration of t-PA in normal human acidified plasma is found to be 4.0 ± 1.8 (SD) ng/ml. It increases to 12 ng/ml after a tomiquet test, and to 14 ng/ml after strenous physical exercise. In a group of patients with idiopathic thromboembolic disease, the resting t-PA concentration was 5 ng/ml and the post-occlusion value 16 ng/ml. Furthermore, the patients also exhibited a normal post-occlusion rise in the concentration of plasmin-α2-antiplasmin complex. However, in 37% of the post-occlusion patient plasmas, virtually no increase in t-PA could be detected by a specific activity assay. The results indicate that the reason for a defective post-occlusion fibrinolytic activity in a majority of cases may be the presence of increased concentrations of a fast-acting specific t-PA inhibitor.

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PHYSICAL ACTIVITY RELEASES TISSUE PLASMINOGEN ACTIVATOR FROM EXERCISING PARTS OF BODY

10.1055/s-0038-1643117 ◽

1987 ◽

Author(s):

I Keber ◽

K Potisk ◽

D Keber ◽

M Stegnar ◽

N Vene

Keyword(s):

Physical Activity ◽

Plasminogen Activator ◽

Tissue Plasminogen Activator ◽

Fibrinolytic Activity ◽

Venous Occlusion ◽

Clot Lysis ◽

Lysis Time ◽

Tissue Plasminogen ◽

Euglobulin Clot Lysis Time ◽

The Difference

To determine the origin of tissue plasminogen activator (t-PA) release during physical activity, we studied the separate and combined effects of venous occlusion and acute physical activity on t-PA release in arm and leg. In 15 healthy volunteers 20 min venous occlusions of arm and leg were performed simultaneously before physical activity ( maximal stress testing on treadmill)(occlusion I), immediately after physical activity and 45 min later (occlusion II). Blood samples were drawn from unoccluded arm before occlusion and after physical activity, and from occluded arm and leg after occlusion. Fibrinolytic activity was measured by euglobulin clot lysis time (ECLT) and t-PA activity assay. The amount of released t-PA during different stimuli (fibrinolytic potential) was calculated as the difference between post- and prestimulation fibrinolytic activity. Before physical activity there was a great increase in fibrinolytic activity due to t-PA in the occluded arm but no increase in the occluded leg. Physical activity itself caused a similar increase of systemic fibrinolytic activity as arm occlusion locally. After physical activity arm occlusion evoked equally good response than before it. Fibrinolytic activity during leg occlusion behaved differently: there was an increase in t-PA activity in the occluded leg which persisted one hour after physical activity, when systemic fibrinolytic activity already fell to initial level.These results demonstrated that walking and running triggered t-PA release from the leg vessels. Since leg occlusion was not a stimulus for t-PA release, it served only as a method to demonstrate the effect of physical activity.

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