IDENTIFICATION OF A FIBRINOLYTIC DEFECT IN TWO FAMILIES WITH A TENDENCY TO THROMBOSIS

1987 ◽  
Author(s):  
H Ostermann ◽  
S Koenig ◽  
H Pollmann ◽  
U Schmitz-Huebner
Keyword(s):  
Venous Thrombosis ◽  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Venous Occlusion ◽  
Fibrinolytic System ◽  
Tissue Type ◽  
Clot Lysis ◽  
Normal Range ◽  
Before And After ◽  
Euglobulin Clot Lysis Time

We identified two families in whom one member each suffered from deep venous thrombosis and subsequent pulmonary emboli at the age of 15 and 17. We were able to investigate several members of both families with regard to their fibrinolytic system. Blood sampling was done before and after ten minutes of venous occlusion. Parameters measured were euglobulin clot lysis time (ECLT), tissue-type plasminogen activator (t-PA) activity, t-PA concentration and plasminogen activator inhibitor (PAI) activity, besides several other constituents of the coagulation and fibrinolytic system commonly associated with thrombophilia.In the first family six persons could be evaluated. A prolonged ECLT was found in four probands. Three of them had no measurable t-PA activity after stasis, t-PA concentration after stasis was below the normal range in two and borderline in one of them.In the second family 13 members could be invest-gated. Three adults were found to have a prolonged ECLT. Two of these had very low t-PA activity after stasis, with normal increase in t-PA antigen. Their PAI was increased above the normal range. Six children showed no measurable PAI and increased levels of t-PA activity before stasis. After stasis four children had a prolonged ECLT. Two of them had low t-PA antigen levels, while all of them showed normal t-PA activity increases.These findings suggest, that there may be hereditary defects related to activators and inhibitors of the fibrinolytic system in the investigated families. These could possibly be responsible for the occurence of venous thrombosis early in life. However, results in the second family show that not all of the prolonged ECLT values can be explained by changes of t-PA and PAI.

Diurnal Variation of the Fibrinolytic System

1988 ◽  
Vol 59 (03) ◽  
pp. 495-499 ◽  
Author(s):  
V Grimaudo ◽  
J Hauert ◽  
F Bachmahh ◽  
E K O Kruithof
Keyword(s):  
Diurnal Variation ◽  
Plasminogen Activator ◽  
Fibrinolytic Activity ◽  
Significant Proportion ◽  
Plasminogen Activator Inhibitor ◽  
Fibrinolytic System ◽  
Tissue Type ◽  
Clot Lysis ◽  
Euglobulin Clot Lysis Time ◽  
Pai 1

AbstractTo elucidate which component(s) of thei fibrinolytic system is (are) responsible for the diurnal variation of fibrinolytic activity we have studied several parameters of this system in 8 healthy male volunteers during a period of. 24 h. Blood was collected at 8 a. m., 10 a. m., 12 a. m., 4 p.m., 8 p.m. and 8 a. m. next morning. The following tests were performed: euglobulin clot lysis time (ECLT), fibrinolytic activity of euglobulins on fibrin plates in the presence and absence of blocking antibodies to tissue-type plasminogen activator (t-PA) and/or urokinase (u-PA), overall plasminogen activator inhibitor (PAI) activity, antigen levels of t-PA, u-PA and PAI-I and zymography of the euglobulin fraction after SDS-PAGE. From 8-10 a. m. to 4-8 p. m., total fibrinolytic activity increased by 1l3% (p <0.01) or 71%h (p <0.01) when measured by ECIX or by fibrin plate assay, respectively. The immunoquenching experiments showed that this increase was entirely due to t-PA related activity whereas u-PA activity and t-PA/u-PA independent activity remained constant during the day. Average antigen levels of u-PA and t-PA in the afternoon were 6% and 25% lower than those measured in the morning. During this period, overall PAI activity and PAI-1 antigen decreased by 3l% (p <0.01) and 52% (p <0.01) respectively. Electrophoretic-zymographic analysis of_ the euglobulins revealed that throughout the day the majority of t-PA was present in the form of the 110 kDa t-PA/PAI-I complex. The intensity of this cornplex was lowest in the afternoon. Free t-PA was almost undetectable in morning samples, but constituted a significant proportion of total t-PA in the afternoon. The diurnal increase of fibrinolytic activity, therefore, is not due to an augmentation of antigen levels of t-PA and/or u-PA but to a decline of those of PAI-1.

Reperfusion After Venous Occlusion Caused Transient Increase in Plasminogen Activator Inhibitor-1 in Systemic Circulation

1998 ◽  
Vol 4 (2) ◽  
pp. 133-137
Author(s):  
Nobuo Nagai ◽  
Tetsumei Urano ◽  
Yumiko Takada ◽  
Akikazu Takada
Keyword(s):  
Plasminogen Activator ◽  
Fibrinolytic Activity ◽  
Plasminogen Activator Inhibitor ◽  
Systemic Circulation ◽  
Venous Occlusion ◽  
Transient Increase ◽  
Clot Lysis ◽  
Plasminogen Activator Inhibitor 1 ◽  
Euglobulin Clot Lysis Time ◽  
Pai 1

From the point of local regulation, we investigated fibrinolytic activity both in local and systemic circulations, using a venous occlusion test as a stimulus of tissue plasmin ogen activator (t-PA) release in human volunteers. Blood samples were taken before, during, and after venous occlusion from the occluded arm as trapped blood and the unoccluded arm as blood of systemic circulation. In these samples, fibri nolytic activity by euglobulin-clot lysis time and related factors in t-PA and plasminogen activator inhibitor-1 (PAI-1) were measured. Venous occlusion increased fibrinolytic activity ac companied by an increase in t-PA without an increase in PAI-1 on the occluded arm. The fibrinolytic activity on the unoc cluded arm did not change. Five minutes after reperfusion, however, a transient increase in PAI-1 and no change of fibri nolytic activity were observed in the unoccluded arm. Transient increase of PAI-1 after reperfusion was also observed in the occluded arm. These results suggested that increased t-PA by venous occlusion was neutralized by released PAI-1 after reperfusion. Key Words: Tissue-plasminogen activator— Euglobulin-clot lysis time—Fibrinolysis.

scholarly journals Plasminogen activator inhibitor 1: development of a radioimmunoassay and observations on its plasma concentration during venous occlusion and after platelet aggregation

Blood ◽  
1987 ◽  
Vol 70 (5) ◽  
pp. 1645-1653 ◽  
Author(s):  
EK Kruithof ◽  
G Nicolosa ◽  
F Bachmann
Keyword(s):  
Platelet Aggregation ◽  
Plasminogen Activator ◽  
Platelet Rich Plasma ◽  
Plasminogen Activator Inhibitor ◽  
Venous Occlusion ◽  
Tissue Type ◽  
Plasminogen Activator Inhibitor 1 ◽  
Bovine Endothelial Cell ◽  
Before And After ◽  
Pai 1

Abstract To study the effect of plasminogen activator inhibitors (PAI) on fibrinolysis it is essential to be able to specifically measure these proteins in plasma. To this end PAI-1 was purified from cortisol- stimulated HT 1080 fibrosarcoma cells and antisera raised in rabbits. The immunologic relationship of the purified inhibitor to PAI-1 in plasma and platelet extracts was established by immunoblotting and regular and reverse fibrin zymography. Furthermore, the purified product could be immunoprecipitated with antibodies to human or bovine endothelial cell-derived PAI-1. A radioimmunoassay was developed that measures both free and tissue-type plasminogen activator (t-PA)-bound PAI-1 in plasma and has an effective range of 8 to 250 ng/mL. PAI-1 antigen levels showed a twofold increase after 20 minutes of venous occlusion, partially due to hemoconcentration. Approximately one quarter of PAI-1 before and after venous occlusion is derived from platelets. After correction for hemoconcentration and the contribution of platelets to plasma PAI-1 levels, a still significant increase in PAI-1 levels was noted during venous occlusion, which suggests that the local vascular bed releases PAI-1. Concomitant with PAI-1, t-PA antigen levels increased eightfold and fibrinolytic activity 18-fold after 20 minutes of venous occlusion. PAI-1 and t-PA levels tend to augment with age: in a group of older healthy volunteers (mean age, 53 years) PAI-1 levels were twice and t-PA levels 1.7 times higher than those in a group with a mean age of 29 years. Determination of PAI-1 antigen levels before and after platelet aggregation demonstrated that 85% of PAI-1 in platelet-rich plasma is associated with platelets. The average amount of PAI-1 per platelet was 0.3 fg/platelet, ie, 4,000 molecules per platelet.

scholarly journals Plasminogen activator inhibitor 1: development of a radioimmunoassay and observations on its plasma concentration during venous occlusion and after platelet aggregation

Blood ◽  
1987 ◽  
Vol 70 (5) ◽  
pp. 1645-1653
Author(s):  
EK Kruithof ◽  
G Nicolosa ◽  
F Bachmann
Keyword(s):  
Platelet Aggregation ◽  
Plasminogen Activator ◽  
Platelet Rich Plasma ◽  
Plasminogen Activator Inhibitor ◽  
Venous Occlusion ◽  
Tissue Type ◽  
Plasminogen Activator Inhibitor 1 ◽  
Bovine Endothelial Cell ◽  
Before And After ◽  
Pai 1

To study the effect of plasminogen activator inhibitors (PAI) on fibrinolysis it is essential to be able to specifically measure these proteins in plasma. To this end PAI-1 was purified from cortisol- stimulated HT 1080 fibrosarcoma cells and antisera raised in rabbits. The immunologic relationship of the purified inhibitor to PAI-1 in plasma and platelet extracts was established by immunoblotting and regular and reverse fibrin zymography. Furthermore, the purified product could be immunoprecipitated with antibodies to human or bovine endothelial cell-derived PAI-1. A radioimmunoassay was developed that measures both free and tissue-type plasminogen activator (t-PA)-bound PAI-1 in plasma and has an effective range of 8 to 250 ng/mL. PAI-1 antigen levels showed a twofold increase after 20 minutes of venous occlusion, partially due to hemoconcentration. Approximately one quarter of PAI-1 before and after venous occlusion is derived from platelets. After correction for hemoconcentration and the contribution of platelets to plasma PAI-1 levels, a still significant increase in PAI-1 levels was noted during venous occlusion, which suggests that the local vascular bed releases PAI-1. Concomitant with PAI-1, t-PA antigen levels increased eightfold and fibrinolytic activity 18-fold after 20 minutes of venous occlusion. PAI-1 and t-PA levels tend to augment with age: in a group of older healthy volunteers (mean age, 53 years) PAI-1 levels were twice and t-PA levels 1.7 times higher than those in a group with a mean age of 29 years. Determination of PAI-1 antigen levels before and after platelet aggregation demonstrated that 85% of PAI-1 in platelet-rich plasma is associated with platelets. The average amount of PAI-1 per platelet was 0.3 fg/platelet, ie, 4,000 molecules per platelet.

The Increase of Leg Fibrinolytic Potential After Reduction of Hydrostatic Stimulus

1983 ◽  
Vol 50 (03) ◽  
pp. 731-734 ◽  
Author(s):  
Dušan Keber
Keyword(s):  
Plasminogen Activator ◽  
Venous Occlusion ◽  
Clot Lysis ◽  
The Third ◽  
Lysis Time ◽  
Before And After ◽  
Euglobulin Clot Lysis Time ◽  
The Difference ◽  
Fibrinolytic Potential ◽  
Clot Lysis Time

SummaryEleven patients were studied sequentially from the beginning of recumbency due to trauma up to the complete mobilization. The first blood sampling was performed 12 hr to 4 days after injury, the second after 12 to 33 days of recumbency and the third after one or more months of mobilization. The blood was drawn each time before and after venous occlusion of the arm and the leg for 20 min. Fibrinolytic potential was calculated as the difference between post- and preocclusion values of plasminogen activator activity, measured with the euglobulin clot lysis time (ECLT) and on fibrin plates. The results showed that fibrinolytic potential of legs after the period of recumbency was approaching that of the arms, being ten times higher as measured with ECLT and five times higher as measured on fibrin plates in comparison with the period after mobilization. It was concluded that hydrostatic pressure was the main, if not the only factor responsible for the difference in the content of plasminogen activator in veins of arms and legs and their fibrinolytic potential.

Reproducibility of Fibrinolytic Response to Venous Occlusion in Healthy Subjects

1995 ◽  
Vol 73 (03) ◽  
pp. 453-457 ◽  
Author(s):  
Mojca Stegnar ◽  
Alenka Mavri
Keyword(s):  
Plasminogen Activator ◽  
Healthy Subjects ◽  
Correlation Coefficients ◽  
Plasminogen Activator Inhibitor ◽  
Venous Occlusion ◽  
Repeated Measurements ◽  
Tissue Type ◽  
Clot Lysis ◽  
Activator Inhibitor Type ◽  
Activator Inhibitor

SummaryFibrinolytic response to venous occlusion is used to assess the efficiency of the fibrinolytic system. Reproducibility of fibrinolytic variables after 20 min upper arm venous occlusion was investigated in 40 apparently healthy subjects tested twice in a period of 11-23 (mean 15) days. Resting and post-venous occlusion euglobulin clot lysis time, tissue-type plasminogen activator (t-PA) activity, t-PA antigen, plasminogen activator inhibitor (PAI) activity and plasminogen activator inhibitor type 1 (PAI-1) antigen determined on the two occasions did not differ significantly. Positive correlation coefficients for variables before (r=0.43-0.74, all p<0.01) and after venous occlusion (r=0.07-0.66) indicated low to moderate associations between repeated measurements. Differences between repeated measurements relative to the initial measurement were greater after venous occlusion than before venous occlusion and were for euglobulin activity 41 (0-826)%, t-PA activity 27 (2-398)%, and for t-PA antigen 27 (0-179)% (medians and ranges). Poor responses were defined by the lowest (euglobulin activity, t-PA activity and t-PA antigen) or the highest (PAI activity) fifth percentile of the distribution. Almost no agreement between poor responses was observed: poor responses at the first occasion were not determined in the same subjects when re-examined after two weeks. It was concluded that due to relatively low reproducibility of the variables measured after venous occlusion the test needs improvement in order to be potentially clinically useful.

Veränderungen des fibrinolytischen Systems bei Patienten mit peripheren arteriellen Durchblutungsstörungen

VASA ◽  
1999 ◽  
Vol 28 (2) ◽  
pp. 106-111 ◽  
Author(s):  
Poredos ◽  
Stegnar ◽  
Gacnik
Keyword(s):  
Clinical Stage ◽  
Arterial Disease ◽  
Venous Occlusion ◽  
Fibrinolytic System ◽  
Lower Limbs ◽  
Tissue Type ◽  
Clot Lysis ◽  
Before And After ◽  
Atherosclerotic Process ◽  
Peripheral Arterial

Background: The fibrinolytic system may play an important role in the development and progression of peripheral arterial occlusive disease. Patients and methods: The fibrinolytic system of the whole blood and a diseased leg was investigated in twenty men with chronic peripheral atherosclerotic occlusive arterial disease (PAOD, clinical stage II according to Fontaine), aged from 46 to 66 years (mean age = 55.3 years). The diagnosis of PAOD was established by clinical examination and segmental systolic blood pressure measurements using a Doppler ultrasound detector. Twenty age-matched (mean age = 53.4 years) male volunteers with normal arterial circulation of the lower limbs and without risk factors of atherosclerosis, served as controls. In both groups fibrinolytic system was investigated in basal conditions and during provocation. Release of tissue-type plasminogen activator (t-PA) was provoked by 20 min venous occlusion of the arm and the leg and by infusion of DDAVP (1-desamino-8-D-arginine-vasopressin, 0.4 ug/kg of body weight). Blood samples were obtained from the arm and the leg before and after each stimulus. The fibrinolytic parameters: euglobulin clot lysis time, t-PA activity (amidolytic assay) and antigen (ELISA) and t-PA inhibitor (PAI) activity (amidolytic assay) were determined. Results: With the exception of a boderline increase in PAI activity in patients, no other differences between the two groups were observed in basal conditions. The most prominent deterioration of the fibrinolytic system detected in male PAOD patients was a significantly higher residual PAI activity registered during venous occlusion of the arm and two minutes after combined stimulation. Two minutes after combined stimulation (DDAVP and venous occlusion of the arm) significantly lower t-PA activity was observed in patients. In patients t-PA antigen response to venous occlusion and DDAVP was not significantly different from the response observed in healthy volunteers. The fibrinolytic response of the leg to venous occlusion was poor and after DDAVP application it was comparable to the arm. The fibrinolytic response of the diseased leg in men was not significantly different from the healthy leg. Conclusion: The results of our study indicate that alteration of the fibrinolytic system in atherosclerotic disease is predominantly a generalised phenomenon and is not directly related to a local atherosclerotic process.

Fibrinolytic Activity in Chinese Patients with Diabetes or Hyperlipidemia in Comparison with Healthy Controls

1991 ◽  
Vol 65 (01) ◽  
pp. 003-006 ◽  
Author(s):  
Chao Hung Ho ◽  
Tjin Shing Jap
Keyword(s):  
Plasminogen Activator ◽  
Fibrinolytic Activity ◽  
Plasminogen Activator Inhibitor ◽  
Venous Occlusion ◽  
Chinese Patients ◽  
Tissue Type ◽  
Diabetic Patients ◽  
Healthy Controls ◽  
Before And After ◽  
Patients With Diabetes

SummaryPlasma tissue-type plasminogen activator (tPA), plasminogen activator inhibitor (PAI) and euglobulin lysis time (ELT) were determined before and after the venous occlusion test (VOT) in 3 groups of patients with mean age about 60 years: 29 diabetic patients (D group), 8 hyperlipidemic patients (H group) and 19 healthy controls (C group). In the D and H groups, the mean of morning tPA was significantly higher than that of the C grogp, but the means of PAI were not significantly different among the 3 groups. ELI was significantly shortened and tPA was markedly increased after the VOT in all 3 groups whereas PAI had not significantly changed. In conclusion, high tPA activity and good fibrinolytic response without significant change of PAI .activity were found in the diabetic and hyperlipidemic patients, and no definite impairment of the fibrinolytic activity could be found in the Chinese patients with diabetes and hyperlipidemia. This might be one of the reasons why the Chinese has low incidence of thromboembolic diseases.

Effect of Physiological Concentrations of Vasopressin on Components of the Fibrinolytic System

1989 ◽  
Vol 61 (02) ◽  
pp. 298-300 ◽  
Author(s):  
H Hariman ◽  
P J Grant ◽  
J R Hughes ◽  
N A Booth ◽  
J A Davies ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Thrombin Generation ◽  
Plasminogen Activator Inhibitor ◽  
Tissue Type ◽  
Clot Lysis ◽  
Type Plasminogen Activator ◽  
Plasma Factor ◽  
Euglobulin Clot Lysis Time ◽  
Small Rise ◽  
Pai 1

SummaryHigh physiological concentrations of plasma vasopressin (aVP) when achieved by infusion cause an increase in plasma factor VIII coagulant activity and shortening of the euglobulin clot lysis time (ECLT). To investigate the effects of aVP on components of the fibrinolytic pathway and on thrombin generation, t healthy volunteers were infused with saline for 30 min followed by aVP for L hour and blood samples taken every 30 min for measurement of aVR ECtf tissue-type plasminogen activator (t-PA), t-PA inhibition (tPA-I), plasminogen activator inhibitor L (PAI-1 Ag), activated partial thromboplastin time (APTT), fibrinopeptide A (FPA), fibrinopeptide B 15-42 (FPBß 15-42) and crosslinked fibrin breakdown products (XL-FDP). Plasma aVP rose to a median of 75 pg/ml after 90 min and fell to 13.8 pdml 30 min later. The APTT fell from 43.5 to 35 sec (p <0.01) but there was no change in plasma FPA or in XL-FDP. Plasminogen activator activity (106/ECLT2) increased from 25 to 736 units (p <0.01) and t-PA from 200 to 1012 mlU/ml (p <0.01). tPA-I fell from 8.0 to 2.7 IU/ml at 90 min (p <0.05) but PAI-1 Ag remained unchanged. Plasma FPBß 15-42 was 2.4 and 1.2 pmol/ml before infusion with aVP and showed a small rise to 3.5 pmol/ml after 60 min (p <0.05). The results show the effects of aVP on fibrinolysis are mediated by an increase in t-PA. In the absence of thrombin generation the rise in t-PA was not accompanied by changes in XL-FDP.

Differential Role of Components of the Fibrinolytic System in the Formation and Removal of Thrombus Induced by Endothelial Injury

1999 ◽  
Vol 81 (04) ◽  
pp. 601-604 ◽  
Author(s):  
Hiroyuki Matsuno ◽  
Osamu Kozawa ◽  
Masayuki Niwa ◽  
Shigeru Ueshima ◽  
Osamu Matsuo ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Thrombus Formation ◽  
Endothelial Injury ◽  
Fibrinolytic System ◽  
Tissue Type ◽  
Clot Lysis ◽  
Wild Type ◽  
Type Plasminogen Activator ◽  
Pai 1

SummaryThe role of fibrinolytic system components in thrombus formation and removal in vivo was investigated in groups of six mice deficient in urokinase-type plasminogen activator (u-PA), tissue-type plasminogen activator (t-PA), or plasminogen activator inhibitor-1 (PAI-1) (u-PA-/-, t-PA-/- or PAI-1-/-, respectively) or of their wild type controls (u-PA+/+, t-PA+/+ or PAI-1+/+). Thrombus was induced in the murine carotid artery by endothelial injury using the photochemical reaction between rose bengal and green light (540 nm). Blood flow was continuously monitored for 90 min on day 0 and for 20 min on days 1, 2 and 3. The times to occlusion after the initiation of endothelial injury in u-PA+/+, t-PA+/+ or PAI-1+/+ mice were 9.4 ± 1.3, 9.8 ± 1.1 or 9.7 ± 1.6 min, respectively. u-PA-/- and t-PA-/- mice were indistinguishable from controls, whereas that of PAI-1-/- mice were significantly prolonged (18.4 ± 3.7 min). Occlusion persisted for the initial 90 min observation period in 10 of 18 wild type mice and was followed by cyclic reflow and reocclusion in the remaining 8 mice. At day 1, persistent occlusion was observed in 1 wild type mouse, 8 mice had cyclic reflow and reocclusion and 9 mice had persistent reflow. At day 2, all injured arteries had persistent reflow. Persistent occlusion for 90 min on day 0 was observed in 3 u-PA-/-, in all t-PA-/- mice at day 1 and in 2 of the t-PA-/-mice at day 2 (p <0.01 versus wild type mice). Persistent patency was observed in all PAI-1-/- mice at day 1 and in 5 of the 6 u-PA-/- mice at day 2 (both p <0.05 versus wild type mice). In conclusion, t-PA increases the rate of clot lysis after endothelial injury, PAI-1 reduces the time to occlusion and delays clot lysis, whereas u-PA has little effect on thrombus formation and spontaneous lysis.

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