Increased Euglobulin Fibrinolytic Potential in Women on Oral Contraceptives Low in Oestrogen – Levels of Extrinsic and Intrinsic Plasminogen Activators, Prekallikrein, Factor XII, and C1-Inactivator

1985 ◽  
Vol 54 (02) ◽  
pp. 454-459 ◽  
Author(s):  
Jørgen Jespersen ◽  
Cornelis Kluft
Keyword(s):  
Plasminogen Activator ◽  
Oral Contraceptives ◽  
Fibrinolytic Activity ◽  
Tissue Type ◽  
Factor Xii ◽  
Type Plasminogen Activator ◽  
The Difference ◽  
Normal Women ◽  
Fibrinolytic Potential ◽  
Increased Activity

SummaryComponents of the fibrinolytic system were studied in samples of plasma from 15 normal, young women and from 11 women taking oral contraceptives containing 30 μg ethinyl oestradiol and 150 μg levo-norgestrel. Fibrinolytic activity of euglobulins precipitated at pH 5.9 was higher than normal in the hormone group, with significant fluctuations related to the cycle. Normal women showed only minor fluctuations. The concentration of C1-inactivator was lower in euglobulins of the hormone group. However, the difference in fibrinolytic activity was retained, when C1-inactivator was inactivated with sodium flufenamate. Fluctuations of the extrinsic (tissue-type) plasminogen activator (t-PA) activity parallelled those of the euglobulin activity.The intrinsic plasminogen activator activity (dextran sulphate precipitated euglobulin) was significantly increased in the hormone group and the cyclic pattern differed from that of the normal group. The increased activity was factor XII-dependent. Plasma prekallikrein did not differ. The factor XII level was increased in the hormone group but this could not explain the increased intrinsic fibrinolytic activity, suggesting an increase in the quantity of an additional factor XII-dependent proactivator.

The Diurnal Increase in Euglobulin Fibrinolytic Activity in Women Using Oral Contraceptives and in Normal Women, and the Generation of Intrinsic Fibrinolytic Activity

1986 ◽  
Vol 56 (02) ◽  
pp. 183-188 ◽  
Author(s):  
Jørgen Jespersen
Keyword(s):  
Plasminogen Activator ◽  
Oral Contraceptives ◽  
Fibrinolytic Activity ◽  
Total Activity ◽  
Tissue Type ◽  
Tissue Type Plasminogen Activator ◽  
Type Plasminogen Activator ◽  
Diurnal Fluctuations ◽  
Normal Women ◽  
The Individual

SummaryThe diurnal fluctuations in plasma euglobulin fibrinolytic activity in women on oral contraceptives and in normal women showed similar patterns of increase. Following inactivation of inhibitors by flufenamate the individual increases and the evening levels did not differ. The diurnal increase was related to an increase in extrinsic (tissue-type) plasminogen activator (t-PA) activity, which contributes little to the total activity of the euglobulin fraction but induces an activation of the intrinsic system.

scholarly journals Plasminogen activators in dextran sulfate-activated euglobulin fractions: a molecular analysis of factor XII- and prekallikrein- dependent fibrinolysis

Blood ◽  
1989 ◽  
Vol 73 (4) ◽  
pp. 994-999
Author(s):  
J Hauert ◽  
G Nicoloso ◽  
WD Schleuning ◽  
F Bachmann ◽  
M Schapira
Keyword(s):  
Plasminogen Activator ◽  
Fibrinolytic Activity ◽  
Dextran Sulfate ◽  
Plasminogen Activators ◽  
Contact System ◽  
Tissue Type ◽  
Plasma Kallikrein ◽  
Factor Xii ◽  
Single Chain ◽  
Type Plasminogen Activator

To elucidate the mechanism by which activation of the contact system of blood coagulation leads to expression of fibrinolytic activity, we have determined the molecular characteristics of the plasminogen activators present in dextran sulfate-treated euglobulin fractions by electrophoretic-zymographic analysis and specific immunoadsorption. In addition to free and protease inhibitor-bound tissue-type plasminogen activator (t-PA), dextran sulfate precipitates of euglobulins contained the complex formed between plasma kallikrein and C1-inhibitor, an indicator of prekallikrein activation. These precipitates also contained substantial fibrinolytic activity related to urinary-type plasminogen activator (u-PA). Autoradiographic analysis was then used to evaluate the cleavage of 125I-single-chain u-PA (prourokinase) in dextran sulfate euglobulins as well as after exposure to kallikrein or beta-factor XIIa. This analysis supported the conclusion that plasma kallikrein-mediated cleavage and activation of single-chain u-PA is the mechanism operative for the development of lytic activity in euglobulin precipitates following activation of the contact system.

Effect of exercise and oral contraceptive agents on fibrinolytic potential in trained females

1984 ◽  
Vol 56 (4) ◽  
pp. 906-913 ◽  
Author(s):  
I. A. Huisveld ◽  
C. Kluft ◽  
A. J. Hospers ◽  
M. J. Bernink ◽  
W. B. Erich ◽  
...  
Keyword(s):  
Oral Contraceptive ◽  
Plasminogen Activator ◽  
Antithrombin Iii ◽  
Tissue Type ◽  
Factor Xii ◽  
High Molecular Weight Kininogen ◽  
Contraceptive Agents ◽  
Type Plasminogen Activator ◽  
Synthetic Estrogens ◽  
Fibrinolytic Potential

It has been shown that physical exercise increases blood fibrinolytic potential, primarily by inducing a release of extrinsic plasminogen activator from the vessel wall. Synthetic estrogens have also been reported to influence fibrinolytic activity. The effect of exercise and the possible additional effect of oral contraceptive agents (OCA) on the fibronolytic system were studied in 20 competitive female rowers. Ten females used OCA (users), and 10 others did not (nonusers). All participants were subjected to standardized exhaustive exercise. Preexercise data revealed higher factor XII, total plasminogen, and free plasminogen levels together with a significantly lower C1-inactivator level in the group of users. No differences were observed in prekallikrein, high-molecular-weight kininogen, alpha 2-antiplasmin, alpha 2-macroglobulin, antithrombin III, and histidine-rich glycoprotein plasma levels. The factor XII-dependent fibrinolytic activator activity and the extrinsic (tissue-type) plasminogen activator were significantly higher; however, the urokinase-like fibrinolytic activator activity was significantly lower. These observations suggest a greater susceptibility to activation of the fibrinolytic pathways during OCA medication. Exercise resulted in a decrease of all factors under study but an increase in all fibrinolytic activities. No differences were observed between the two groups in the percentages of change that occurred with exercise.

Inhibition of Tissue-Type Plasminogen Activator in Plasma of Women Using Oral Contraceptives and in Normal Women During a Menstrual Cycle

1986 ◽  
Vol 55 (03) ◽  
pp. 388-389 ◽  
Author(s):  
J Jespersen ◽  
C Kluft
Keyword(s):  
Menstrual Cycle ◽  
Plasminogen Activator ◽  
Oral Contraceptives ◽  
Tissue Type ◽  
Tissue Type Plasminogen Activator ◽  
Type Plasminogen Activator ◽  
Normal Women ◽  
Ethinyl Oestradiol

SummaryTissue-type plasminogen activator (t-PA) inhibition in plasma was assessed in 15 normal women and in 10 women using oral contraceptives (OC) containing 30 μg ethinyl oestradiol and 150 μg levo-norgestrel. The levels of t-PA inhibition were significantly lower in the OC group with marked fluctuations related to the hormone cycle. Normal women had only minor fluctuations.

scholarly journals Plasminogen activators in dextran sulfate-activated euglobulin fractions: a molecular analysis of factor XII- and prekallikrein- dependent fibrinolysis

Blood ◽  
1989 ◽  
Vol 73 (4) ◽  
pp. 994-999 ◽  
Author(s):  
J Hauert ◽  
G Nicoloso ◽  
WD Schleuning ◽  
F Bachmann ◽  
M Schapira
Keyword(s):  
Plasminogen Activator ◽  
Fibrinolytic Activity ◽  
Dextran Sulfate ◽  
Plasminogen Activators ◽  
Contact System ◽  
Tissue Type ◽  
Plasma Kallikrein ◽  
Factor Xii ◽  
Single Chain ◽  
Type Plasminogen Activator

Abstract To elucidate the mechanism by which activation of the contact system of blood coagulation leads to expression of fibrinolytic activity, we have determined the molecular characteristics of the plasminogen activators present in dextran sulfate-treated euglobulin fractions by electrophoretic-zymographic analysis and specific immunoadsorption. In addition to free and protease inhibitor-bound tissue-type plasminogen activator (t-PA), dextran sulfate precipitates of euglobulins contained the complex formed between plasma kallikrein and C1-inhibitor, an indicator of prekallikrein activation. These precipitates also contained substantial fibrinolytic activity related to urinary-type plasminogen activator (u-PA). Autoradiographic analysis was then used to evaluate the cleavage of 125I-single-chain u-PA (prourokinase) in dextran sulfate euglobulins as well as after exposure to kallikrein or beta-factor XIIa. This analysis supported the conclusion that plasma kallikrein-mediated cleavage and activation of single-chain u-PA is the mechanism operative for the development of lytic activity in euglobulin precipitates following activation of the contact system.

Physical Exercise Induces Enhancement of Urokinase-Type Plasminogen Activator (u-PA) Levels in Plasma

1991 ◽  
Vol 65 (01) ◽  
pp. 082-086 ◽  
Author(s):  
G Dooijewaard ◽  
A de Boer ◽  
P N C Turion ◽  
A F Cohen ◽  
D D Breimer ◽  
...  
Keyword(s):  
Physical Exercise ◽  
Plasminogen Activator ◽  
Maximal Exercise ◽  
Normal Values ◽  
Bicycle Ergometer ◽  
Tissue Type ◽  
Healthy Male ◽  
Type Plasminogen Activator ◽  
Urokinase Type Plasminogen Activator ◽  
Fibrinolytic Potential

SummaryThe enhancement of the blood fibrinolytic potential by physical exercise is generally attributed to the release of tissue-type plasminogen activator (t-PA) from the vessel wall. In this study we have investigated the possible contribution of urokinase-type plasminogen activator (u-PA).Six healthy male volunteers (age 21–25 years) were screened for their ability to perform maximal exercise for their age-group for 12 min on a bicycle ergometer. Subsequently, on one occasion they were required to remain supine for 2 h (from 8.30 a. m. onwards) and on another they performed maximal exercise (from 9.00 a.m. onwards). During exercise an increase in u-PA antigen and plasmin-activatable pro-urokinase (proUK) activity, concurrent with t-PA antigen and euglobulin t-PA activity, was observed in all six volunteers, while at rest these parameters remained unaffected. Mean u-PA- and t-PA antigen increased, respectively, from 4.2 ± 1.0 ng/ml and 5.8 ± 2.1 ng/ml before exercise to 9.8 ± 3.0 ng/ml and 18.3 ± 3.8 ng/ml (peak). Mean plasminactivatable proUK activity and t-PA activity increased, respectively, from 2.1 ± 0.4 ng/ml and 0.3 ± 0.2 ng/ml before exercise to 4.3 ± 1.7 ng/ml and 7.2 ± 4.0 ng/ml (peak). The increases were statistically significant throughout (paired t-test, pre vs post, antigen P <0.005 and activity P <0.02). After cessation of exercise u-PA and t-PA declined concurrently to normal values with a 50"/" decay in about 5 min. In conclusion, we found that both u-PA antigen and plasmin-activatable proUK activity are, concurrently with t-PA, enhanced upon exercise and, therefore, we consider that u-PA also contributes to – and co-operates in – the enhancement of the blood fibrinolytic potential and activity under these conditions.

On the Fibrinolytic System in Aged Rats, and Its Reactivity to Endotoxin and Cytokines

1992 ◽  
Vol 67 (06) ◽  
pp. 697-701 ◽  
Author(s):  
J J Emeis ◽  
A Brouwer ◽  
R J Barelds ◽  
M A Horan ◽  
S K Durham ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Fibrinolytic Activity ◽  
Fibrinolytic System ◽  
Tissue Type ◽  
High Dose ◽  
Base Line ◽  
Aged Rats ◽  
Tissue Type Plasminogen Activator ◽  
Young Rats ◽  
Type Plasminogen Activator

SummaryAged rats are more susceptible to endotoxin-induced effects, including microthrombosis and platelet aggregation, than are young rats. To investigate whether changes in the fibrinolytic system might be involved, we investigated the fibrinolytic activity in plasma euglobulin fractions and tissues (lung and heart) of young (6-months old) and aged (24-months old) rats under baseline conditions and after challenge with endotoxin. Aged rats had lower plasma levels of tissue-type plasminogen activator (t-PA) and of urokinase-type PA (u-PA) activity. PA inhibitor (PAI) activity was higher in the plasma of aged rats, as was t-PA activity in lung and heart.Rats were treated with either a low dose (1 μg/kg) or a high dose (10 mg/kg) of endotoxin. Both treatments induced a transient phase of increased blood fibrinolytic activity, as evidenced by higher levels of tissue-type plasminogen activator (t-PA) activity and decreased levels of PA inhibitor (PAI) activity. Over time, the fibrinolytic activity decreased, probably due to increased levels of PA inhibitor.Both the early increase in t-PA activity, and the subsequent increase in PAI activity, were more pronounced in the aged rats, as compared with the younger rats, after the high dose of endotoxin. The aged rats also responded to an injection of interleukin-1β or tumor necrosis factor-α with a larger increase of PAI activity than did the younger rats.Together the data suggest that, compared to young rats, aged rats have a decreased base-line plasma fibrinolytic activity, while their fibrinolytic system is more responsive to challenge by endotoxin and cytokines.

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