Download PDF
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
1   The 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
2   The Gaubius Institute, Division of Health Research TNO, Leiden, The Netherlands
› Author Affiliations
Further Information

Publication History

Received 21 October 1983

Accepted 13 May 1985

Publication Date:
18 July 2018 (online)

  PDF Download  Permissions and Reprints

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
 

  • 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
    PubMedGoogle Scholar
  • 2 Wessler S. Thrombosis and sex hormones: a perplexing liaison. J Lab Clin Med 1980; 96: 757-761
    PubMedGoogle Scholar
  • 3 Brakman P, Astrup T. Effect of female hormones, used as oral contraceptives, on the fibrinolytic system in blood. Lancet 1964; 02: 10-12
    PubMedGoogle Scholar
  • 4 Brakman P, Albrechtsen OK, Astrup T. Blood coagulation, fibrinolysis, and contraceptive hormones. JAMA 1967; 199: 69-74
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 6 Brakman P, Sobrero AJ, Astrup T. Effects of different systemic contraceptives on blood fibrinolysis. Am J Obstet Gynecol 1970; 106: 187-192
    CrossrefPubMedGoogle Scholar
  • 7 Hedlin AM. The effect of oral contraceptive estrogen on blood coagulation and fibrinolysis. Thrombos Diathes Haemorrh 1975; 33: 370-378
    PubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 16 Olesen ES. Fibrinolytic activity derived from guinea pig serum by peptone. Acta Physiol Scand 1957; 41: 187-193
    CrossrefPubMedGoogle Scholar
  • 17 Kluft C. Studies on the fibrinolytic system in human plasma: quantitative determination of plasminogen activators and proactivators. Thromb Haemostas 1979; 41: 365-383
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 19 Wijngaards G, Kluft C, Groeneveld E. Demonstration of urokinase-related fibrinolytic activity in human plasma. Br J Haematol 1982; 51: 165-169
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 24 Astrup T, Kok P. Assay and preparation of a tissue plasminogen activator. Meth Enzym 1970; 19: 821-834
    PubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    Google Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 32 Kluft C. Determination of prekallikrein in human plasma: optimal conditions for activating prekallikrein. J Lab Clin Med 1978; 91: 83-95
    PubMedGoogle Scholar
  • 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
    Google Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    Google Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    Google Scholar
  • 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
    CrossrefPubMedGoogle Scholar