Urokinase-Related Fibrinolytic Activity In Human Plasma

1981 ◽  
Author(s):  
G Wijngaards ◽  
C Kluft

Blood represents a complex system containing plasminogenn activators. At present, three different types of plasminogen activator activity are distinguished. It has been assumed that urokinase is not one of the blood activators, but recently an improbably high concentration of urokinase antigenic material has been claimed to be present in plasma.The present study was performed to establish if urokinase activity participates in blood fibrinolysis. This was investigated by measuring quenching by antibodies. The dextran sulphate euglobulin fraction (DEF) of plasma was prepared and its fibrinolytic activity was measured in a clot lysis time method with and without addition of various anti-urokinase immunoglobulin fractions (AUK’s).Considerable quenching of the DEF activity by the AUK’s was found. The quenchings reached maximum values at high antibody concentrations. The quenching curves of the fibrinolytic activity of both urokinase and DEF could be superimposed for each AUK. This quenchable activity was also very sensitive to inhibition by a specific urokinase inhibitor from human placenta. Addition of kaolin to DEF, to include factor XII-dependent fibrinolysis, showed an increase of the fibrinolytic activity which was not quenched by AUK. Double diffusion analyses did not result in the demonstration of urokinase antigen in plasma. This was in agreement with the amount of activity quenched (comparable with about 1 ng urokinase/ml plasma) and the detection limit for a visible precipitation line.These observations indicate that plasma contains urokinase-related activity. This activity is assumed to belong to the factor XII-independent proactivator system.

1981 ◽  
Author(s):  
C Kluft ◽  
G Wijngaards ◽  
A F H Jie

Antibodies to urokinase have been shown to quench part of the fibrinolytic activity of plasma, not involving the extrinsic system. Previously, the intrinsic system has been subdivided into two parts, one dependent and another independent of factor XII, for activation. Both represent approximately 50 BAU activator activity/ml plasma. The aim of this study was to further locate the UK-related activity within the intrinsic fibrinolytic pathways and to delineate its participation in fibrinolysis tests in vitro.Antibodies to UK (AUK) were shown not to quench activities of contact factors such as factor XII, prekallikrein and factor XI in coagulation and chromogenic substrate assays. AUK inhibited in normal plasma, Hageman trait and Fletcher trait plasma a discrete portion of approximately 50 BAU activator activity/ml, apparently the activator activity derived from the factor XII-independent system.Immunoadsorption of plasma with immobilized AUK resulted in a depletion of approximately 50 BAU activator activity/- ml. The contact factors were undisturbed, as were plasminogen and the extrinsic activator. Additions of UK did not restore lost activity, suggesting that AUK has removed the proactivator component.The amount of UK-related activator activity compares to approximately 0.4 IU urokinase activity/ml, and shows a fairly constant level in individuals and is not enhanced by known stimuli for extrinsic activator release.Significant contributions to blood fibrinolytic activity in current assay systems, including the dilute blood clot lysis time method could be demonstrated.


1979 ◽  
Vol 41 (04) ◽  
pp. 745-755 ◽  
Author(s):  
Dušan Keber ◽  
Mojca Stegnar ◽  
Irena Keber ◽  
Bojan Accetto

SummaryFibrinolysis was studied in 10 alpinists during regular physical activity of different intensity. Blood was sampled at rest and after exposure to submaximal workload on the treadmill on three occasions: before and after 6 months physical conditioning (moderate physical activity), and after 6 weeks of an alpinistic expedition (strenuous physical activity). Measurements included submaximal working capacity, fibrinogen, euglobulin clot lysis time (ELT), whole plasma clot lysis time, and estimations derived from ELT - percent increase in fibrinolytic activity after exercise (RFS), and absolute increase in fibrinolytic activity after exercise (PAR).Regular moderate activity increased the resting level of ELT, but strenuous activity decreased is. After each treadmill testing, a marked increase in fibrinolytic activity was observed. RFS was unaltered at all three testings. PAR increased after moderate activity, but decreased after strenuous activity.The results indicate that regular physical activity can lead from enhanced to decreased resting activity of plasminogen activator in blood. It is presumed that increased release of activator during prolonged stress causes partial depletion of endothelial stores with the consequence of decreased activator activity in the blood.


1979 ◽  
Author(s):  
H Greig

The most commonly used test for clinical assessment of fibrinolytic activity is the Euglobulin Lysis Time (ELT). However the normal range is very wide, the long times are inconvenient and detection of inhibition is impossible. An attempt has been made to utilise the acceleration of the ELT when kaolin is present, to devise a test with shorter times, a narrower normal range, and better precision. The Euglobulin lysis time was carried out by a modification of the method of NILSSON and OLOW, after precipitation of the euglobulin in the absence of kaolin (ELT) and in the presence of 1 mg. kaolin/ml. plasma (KELT). In 14 control subjects the mean, SD, and range for the ELT were 168.6’, 54.6’, 84-290’; the corresponding values for the KELT were 60.3’, 8.3’ and 46-74’. However, it was found that there was no correlation between the ELT value and the corresponding KELT (’r’ = -0.021); on the contrary, the longer the ELT, the greater the shortening produced by kaolin and there is a direct correlation between the ELT and the shortening of the lysis time by kaolin; ’r’ = 0.988. It is concluded that the KELT has no value as a clinical measure of fibrinolytic activity; further, the results suggest that kaolin may remove an inhibitor(s) of plasminogen activation as well as initiating Factor XII - mediated plasminogen activation.


1987 ◽  
Author(s):  
I Keber ◽  
K Potisk ◽  
D Keber ◽  
M Stegnar ◽  
N Vene

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.


1981 ◽  
Author(s):  
P Yuen ◽  
H C Rwaan

In an attempt to clarify the conflicting reports of plasminogen activator and lack of fibrinolytic activity in tumor tissues, the fibrinolytic activity of 62 metastatic tumors and 5 tumor thrombi from autopsy and biopsy specimens was studied by the fibrin slide technique. Metastatic tumors involved lymph nodes, liver, lung, brain and ovary. Tumor thrombi were mainly comprised of hepatoma thrombi in branches of either hepatic or portal veins.The lack of fibrinolytic activity was graded according to the focal lysis time of vascular tissues within the tumor and in the case of lymphnodes, lymphatic channels. A complete lack of fibrinolytic activity was observed in metastatic tumors and tumor thrombi, a finding similar to that observed in primary tumors.Immunofluorescent studies on the tumors revealed the presence of antigenic material identical to fibrin, platelets and alpha2 plasmin inhibitor.


1992 ◽  
Vol 68 (04) ◽  
pp. 442-447 ◽  
Author(s):  
S C L Gough ◽  
J Smyllie ◽  
T Sheldon ◽  
P J S Rice ◽  
P J Grant

SummaryRegional circulating plasma levels of fibrinolytic activity were assessed in 15 patients undergoing cardiac catheterisation. The euglobulin clot lysis time (ECLT) was longer in the abdominal aorta (AA) than the inferior vena cava (IVC), (median difference – 17.5 min, p = 0.008). This was associated with higher inhibition of plasminogen activator activity (PAI) in the AA than IVC, – 1.75 IU/ml, p = 0.002. In the venous circulation the ECLT was higher in the peripheral venous sample than in the IVC, –25.5 min, p = 0.003, with higher PAI peripherally than in the IVC, -1.9 IU/ml, p = 0.001. There were no differences in ECLT, PAI, PAI-l:Ag or t-PA:Ag throughout the arterial circulation. These results demonstrate higher fibrinolytic activity with lower inhibitor activity in the venous compared to the arterial circulation. Within the venous circulation fibrinolytic activity is lower peripherally with increased inhibitor activity.


1971 ◽  
Vol 26 (01) ◽  
pp. 083-087 ◽  
Author(s):  
B Lipiński ◽  
A Nowak ◽  
A Odrzywolska ◽  
J Dosiak

SummaryIt was found in the present work that the level of serum fibrinogen degradation products (FDP) determined by the immunoassay method correlated well with the staphylococcal clumping titer in serum (correlation coefficient r = 0.68). The content of FDP in serum of 30 healthy subjects and patients with various diseases did not correlate, however, neither with blood fibrinolytic activity estimated by the euglobulin clot lysis time, nor with fibrinogen content and plasma anticlotting activity. It is concluded, that FDP appear in circulation as a result of local proteolytic degradation of intravascularly deposited fibrin without generalized activation of fibrinolysis.


1979 ◽  
Author(s):  
H.B.W. Greig

The most commonly used test for clinical assessment of fibrinolytic activity is the Euglobulin Lysis Time (ELT). However the normal range is very wide, the long times are inconvenient and detection of inhibition is impossible. An attempt has been made to utilise the acceleration of the ELT when kaolin is present, to devise a test with shorter times, a narrower normal range, and better precision. The Euglobulin lysis time was carried out by a modification of the method of NILSSON and OLOW, after precipitation of the euglobulin in the absence of kaolin (ELT) and in the presence of 1 mg. kaolin/ml,, plasma (KELT). In 14 control subjects the mean, SD, and range for the ELT were 168.6’, 54.6’, 84–290’; the corresponding values for the KELT were 60.3’, 8.3’ and 46-74’. However, it was found that there was no correlation between the ELT value and the corresponding KELT (‘r’ = -0.021); on the contrary, the longer the ELT. the greater the shortening produced by kaolin and there is a direct correlation between the ELT and the shortening of the lysis time by kaolin; ‘r’ - 0.988. It is concluded that the KELT has no value as a clinical measure of fibrinolytic activity;further, the results suggest that kaolin may remove an inhibitor(s) of plasminogen activation as well as initiating Factor XII - mediated plasminogen activation.


1975 ◽  
Author(s):  
R. Chakrabarti ◽  
M. Brozovic ◽  
T. W. Meade ◽  
W. R. S. North ◽  
Y. Stirling

Fibrinolytic activity, coagulation factors I, V, VII and VIII, blood cholesterol and triglyceride levels have been measured in a randomyl selected group of 650 men aged 17–64 and 350 women aged 17–59 working in an industrial population. Fibrinolytic activity (the reciprocal of the dilute blood clot lysis time in hours) decreases significantly (0.003 per annum) with advancing age in men; there is no significant change in women. Factors I and V increase significantly with age in both men and women at about the same rate (1.0% per annum for factor I and 0.6% for factor V), their mean levels in each group being very similar. Factor VIII also increases significantly with age in both sexes up to the age of about 50 years, after which levels continue to rise in men, but fall in women. Factor VII and blood cholesterol levels are lower in young women than in young men; they rise in both sexes, but significantly faster in women than in men (1.1% and 0.4%, respectively for factor VII, for example), so that in older women they are substantially higher than in older men. Triglyceride levels rise with age in both sexes, levels in men being hig er than those in women.


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