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

Jørgen Jespersen; Cornelis Kluft

doi:10.1055/s-0038-1657871

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 1985; 54(02): 454-459
DOI: 10.1055/s-0038-1657871

Original Article

Schattauer GmbH Stuttgart

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

Jørgen Jespersen

¹The Section of Coagulation and Fibrinolysis, Department of Clinical Chemistry, Ribe County Hospital in Esbjerg, and the Section for Thrombosis Research, South Jutland University Centre, Esbjerg, Denmark

,

Cornelis Kluft

²The Gaubius Institute, Division of Health Research TNO, Leiden, The Netherlands

› Institutsangaben

Abstract

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Summary

Components 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.

Keywords

Extrinsic (tissue-type) plasminogen activator - Intrinsic plasminogen (pro)activators - Factor XII - C1-inactivator - Prekallikrein-Menstrual cycle - Oral contraceptives

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Referenzen

References
1 Böttiger LE, Boman G, Eklund G, Westerholm B. Oral contraceptives and thromboembolic disease: effects of lowering oestrogen content. Lancet 1980; 1: 1097-1101
2 Wessler S. Thrombosis and sex hormones: a perplexing liaison. J Lab Clin Med 1980; 96: 757-761
3 Brakman P, Astrup T. Effect of female hormones, used as oral contraceptives, on the fibrinolytic system in blood. Lancet 1964; 02: 10-12
4 Brakman P, Albrechtsen OK, Astrup T. Blood coagulation, fibrinolysis, and contraceptive hormones. JAMA 1967; 199: 69-74
5 Ygge J, Brody S, Korsan-Bengtsen K, Nilsson L. Changes in blood coagulation and fibrinolysis in women receiving oral contraceptives. Comparison between treated and untreated women in a longitudinal study. Am J Obstet Gynecol 1969; 104: 87-98
6 Brakman P, Sobrero AJ, Astrup T. Effects of different systemic contraceptives on blood fibrinolysis. Am J Obstet Gynecol 1970; 106: 187-192
7 Hedlin AM. The effect of oral contraceptive estrogen on blood coagulation and fibrinolysis. Thrombos Diathes Haemorrh 1975; 33: 370-378
8 Meade TW, Haines AP, North WR, Chakrabarti R, Howarth DJ, Stirling Y. Haemostatic, lipid, and blood-pressure profiles of women on oral contraceptives containing 50 μg or 30 μg oestrogen. Lancet 1977; 02: 948-951
9 Jespersen J. Sequential study of plasma euglobulin fibrinolytic activity during the normal menstrual cycle and in women on oral contraceptives low in estrogen. Gynecol Obstet Invest 1983; 15: 266-274
10 Lijnen HR, Hoylaerts M, Collen D. Isolation and characterization of a human plasma protein with affinity for the lysine binding sites in plasminogen. J Biol Chem 1980; 255: 10214-10222
11 Jespersen J, Kluft C. Individual levels of plasma histidine-rich glycoprotein (HRG) during the normal menstrual cycle and in women on oral contraceptives low in oestrogen. Scand J Clin Lab Invest 1982; 42: 563-566
12 Jespersen J, Kluft C. Decreased levels of histidine-rich glycoprotein (HRG) and increased levels of free plasminogen in women on oral contraceptives low in estrogen. Thromb Haemostas 1982; 48: 283-285
13 Gordon EM, Ratnoff OD, Saito H, Donaldson VH, Pensky J, Jones PK. Rapid fibrinolysis, augmented Hageman factor (factor XII) titers, and decreased C1 esterase inhibitor titers in women taking oral contraceptives. J Lab Clin Med 1980; 96: 762-769
14 Jespersen J, Sidelmann J. Individual levels of plasma α₀₂-antiplasmin and α₀₂-macroglobulin during the normal menstrual cycle and in women on oral contraceptives low in oestrogen. Thromb Haemostas 1983; 50: 581-585
15 Rijken DC, Wijngaards G, Welbergen J. Relationship between tissue plasminogen activator and the activators in blood and vascular wall. Thromb Res 1980; 18: 815-830
16 Olesen ES. Fibrinolytic activity derived from guinea pig serum by peptone. Acta Physiol Scand 1957; 41: 187-193
17 Kluft C. Studies on the fibrinolytic system in human plasma: quantitative determination of plasminogen activators and proactivators. Thromb Haemostas 1979; 41: 365-383
18 Astrup T, Rosa AT. A plasminogen proactivator – activator system in human blood effective in the absence of Hageman Factor. Thromb Res 1974; 4: 609-613
19 Wijngaards G, Kluft C, Groeneveld E. Demonstration of urokinase-related fibrinolytic activity in human plasma. Br J Haematol 1982; 51: 165-169
20 Jespersen J, Knudsen LH, Sidelmann J. The use of evacuated glass tubes for collection of blood samples for fibrinolytic assays. Thromb Res 1982; 25: 173-176
21 Brakman P, Albrechtsen OK, Astrup T. A comparative study of coagulation and fibrinolysis in blood from normal men and women. Br J Haematol 1966; 12: 74-85
22 Kluft C, Brakman P, Veldhuyzen-Stolk EC. Screening of fibrinolytic activity in plasma euglobulin fractions on the fibrin plate. In: Davidson JF, Samama MM, Desnoyers PC. (Eds). Progress in Chemical Fibrinolysis and Thrombolysis. Raven Press; New York: 1976. 02 57-65
23 Brakman P, Astrup T. The fibrin plate method for assay of fibrinolytic agents. In: Bang NU, Beller FK, Deutsch E, Mammen EF. (Eds). Thrombosis and Bleeding Disorders. Academic Press; New York: 1971: 332-336
24 Astrup T, Kok P. Assay and preparation of a tissue plasminogen activator. Meth Enzym 1970; 19: 821-834
25 Jespersen J, Astrup T. A study of the fibrin plate assay of fibrinolytic agents: Optimal conditions, reproducibility and precision. Haemostasis 1983; 13: 301-315
26 Kluft C, Jie AFH, Allen RA. Behaviour and quantitation of extrinsic (tissue-type) plasminogen activator in human blood. Thromb Haemostas 1983; 50: 518-523
27 Kluft C. C1-inactivator-resistant fibrinolytic activity in plasma euglobulin fractions: its relation to vascular activator in blood and its role in euglobulin fibrinolysis. Thromb Res 1978; 13: 135-151
28 Kluft C, Jie AFH. Interaction between the extrinsic and intrinsic systems of fibrinolysis. In: Davidson JF, Cepelák V, Samama MM, Desnoyers PC. (Eds). Progress in Chemical Fibrinolysis and Thrombolysis. Churchill Livingstone; Edinburgh: 1979. 4 25-31
29 Rijken DC, Wijngaards G, Welbergen J. Immunological characterization of plasminogen activator activities in human tissues and body fluids. J Lab Clin Med 1981; 97: 477-486
30 Kluft C, Wijngaards G, Jie AFH. Intrinsic plasma fibrinolysis: Involvement of urokinase-related activity in the factor XII-independent plasminogen proactivator pathway. J Lab Clin Med 1984; 103: 408-419
31 Bleeker WK, Van Rosevelt RF, Ufkes JG, Loos JA, Van Mourik JA, Bakker JC. Hypotensive effects of plasma protein fraction. The relation between prekallikrein activator, bradykinin generation, and blood pressure in an animal model. J Lab Clin Med 1982; 100: 540-547
32 Kluft C. Determination of prekallikrein in human plasma: optimal conditions for activating prekallikrein. J Lab Clin Med 1978; 91: 83-95
33 Astrup T, Jespersen J. The fibrin plate assay of fibrinolytic agents – principles and technique. In: Davidson JF, Bachmann F, Bouvier CA, Kruithof EKO. (Eds). Progress in Fibrinolysis. Churchill Livingstone; London: 1983. 6 197-201
34 Kluft C, Michiels JJ, Wijngaards G. Factual or artificial inhibition of fibrinolysis and the occurrence of venous thrombosis in 3 cases of Behcet’s disease. Scand J Haematol 1980; 25: 423-430
35 Kluft C, Trumpi-Kalshoven MM, Deelder AM. Factor XII-independent activator generation in human plasma. In: Davidson JF, Cepelak V, Samama MM, Desnoyers PC. (Eds). Progress in Chemical Fibrinolysis and Thrombolysis. Churchill Livingstone; Edinburgh: 1979. 4 362-367
36 Fisher CA, Schmaier AH, Addonizio VP, Colman RW. Assay of prekallikrein in human plasma: comparison of amidolytic, esterolytic, coagulation, and immunochemical assays. Blood 1982; 59: 963-970
37 Astrup T. Fibrinolysis: An overview. In: Davidson JF, Rowan RM, Samama MM, Desnoyers PC. (Eds). Progress in Chemical Fibrinolysis and Thrombolysis. Raven Press; New York: 1978. 3 01-57
38 Hedner U, Martinsson G. Inhibition of activated Hageman factor (factor XIIa) by an inhibitor of the plasminogen activation (PA inhibitor). Thromb Res 1978; 12: 1015-1023