PDF herunterladen
Thromb Haemost 1983; 50(02): 581-585
DOI: 10.1055/s-0038-1665260
Original Article
Schattauer GmbH Stuttgart

Individual Levels of Plasma α2-Antiplasmin and α2 Macroglobulin During the Normal Menstrual Cycle and in Women on Oral Contraceptives Low in Oestrogen

Jørgen Jespersen
The Section of Coagulation and Fibrinolysis, Department of Clinical Chemistry, Ribe County Hospital in Esbjerg, Esbjerg, Denmark
,
Johannes Sidelmann
The Section of Coagulation and Fibrinolysis, Department of Clinical Chemistry, Ribe County Hospital in Esbjerg, Esbjerg, Denmark
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Received 07. April 1983

Accepted 14. Juni 1983

Publikationsdatum:
18. Juli 2018 (online)

Auch verfügbar auf
  als PDF herunterladen  Lizenzen und Reprints

Summary

Determinations of α2-antiplasmin and α2-macroglobulin were made in plasma samples collected during one normal or hormone induced cycle in 15 normal women and 11 women using oral contraceptives containing 30 μg ethinyl oestradiol and 150 pg levo-norgestrel. The immediate plasmin inhibition test for determination of α2-antiplasmin was modified for application on a centrifugal analyser using the chromogenic peptide substrate Chromozym PL®. α2-Macroglobulin concentration was determined by radial-immunodiffusion. There were no differences between the two groups in the mean concentrations of α2- antiplasmin and α2-macroglobulin, but during the cycle a slight, and statistically significant fall occurred in the α2-antiplasmin concentration in both groups, while the fluctuations of α2- macroglobulin were small and insignificant. Distinctly individual levels of both inhibitors were found to exist. The variations in these during the periods of the cycle fluctuated within a much narrower range than the variation of the total average. The results stress the importance of determining the fluctuations in individual levels in longitudinal studies. These findings exclude variations in the concentrations of these inhibitors as possible sources of a change in the antithrombotic potential caused by oral contraceptives.

Keywords

α2-antiplasmin - α2-antiplasmin assay - α2-macroglobulin - Menstrual cycle - Oral contraceptives
 

  • References

  • 1 Müllertz S, Clemmensen I. The primary inhibitor of plasmin in human plasma. Biochem J 1976; 159: 545-553
    CrossrefPubMedGoogle Scholar
  • 2 Collen D. Identification and some properties of a new fast-reacting plasmin inhibitor in human plasma. Eur J Biochem 1976; 69: 209-216
    CrossrefPubMedGoogle Scholar
  • 3 Moroi M, Aoki N. Isolation and characterization of α2-plasmin inhibitor from human plasma. A novel proteinase inhibitor which inhibits activator-induced clot lysis J Biol Chem 1976; 251: 5956-5965
    PubMedGoogle Scholar
  • 4 Hedner U, Abildgaard U. Report on the joint meeting of the task forces on nomenclature and standards of inhibitors of coagulation and fibrinolysis. Thromb Haemostas 1978; 39: 524-525
    PubMedGoogle Scholar
  • 5 Astrup T. The biological significance of fibrinolysis. Lancet 1956; 3: 565-568
    PubMedGoogle Scholar
  • 6 Stormorken H. The thrombo-haemorrhagic balance. Acta Med Scand 1980; 642 suppl 131-140
    PubMedGoogle Scholar
  • 7 Koie K, Kamiya T, Ogata K, Takamatsu J. α2-Plasmin-inhibitor deficiency (Miyasato disease). Lancet 1978; 2: 1334-1336
    PubMedGoogle Scholar
  • 8 Kluft C, Vellenga E, Brommer EJ P. Homozygous α2-antiplasmin deficiency. Lancet 1979; 2: 206
    PubMedGoogle Scholar
  • 9 Aoki N, Saito H, Kamiya T, Koie K, Sakata Y, Kobakuva M. Congenital deficiency of α2-plasmin inhibitor associated with severe hemorrhagic tendency. J Clin Invest 1979; 63: 877-884
    CrossrefPubMedGoogle Scholar
  • 10 Kluft C, Vellenga E, Brommer EJ P, Wijngaards G. A familial hemorrhagic diatheses in a Dutch family: An inherited deficiency of α2-antiplasmin. Blood 1982; 59: 1169-1180
    PubMedGoogle Scholar
  • 11 Miles LA, Plow EF, Donnelly KJ, Hougie C, Griffin JH. A bleeding disorder due to deficiency of α2-antiplasmin. Blood 1982; 59: 1246-1251
    PubMedGoogle Scholar
  • 12 Brommer EJ P, Gevers Leuven JA, Kluft C, Wijngaards G. Fibrinolytic inhibitor in type II hyperlipoproteinaemia. Lancet 1982; 2: 1066
    PubMedGoogle Scholar
  • 13 Miillertz S. Different molecular forms of plasminogen and plasmin produced by urokinase in human plasma and their relation to protease inhibitor and lysis of fibrinogen and fibrin. Biochem J 1974; 143: 273-283
    CrossrefPubMedGoogle Scholar
  • 14 Harpel PC. Plasmin inhibitor interactions. The effectiveness of α2 Plasmin inhibitor interactions- plasmin inhibitor in the presence of α2-macroglobuIin J Exp Med 1977; 146: 1033-1040
    CrossrefPubMedGoogle Scholar
  • 15 Sakata Y, Aoki N. Cross-linking of α2-antiplasmin inhibitor to fibrin by fibrin-stabilizing factor. J Clin Invest 1980; 65: 290-297
    CrossrefPubMedGoogle Scholar
  • 16 Jespersen J, Kluft C. Decreased levels of histidine-rich glycoprotein (HRG) and increased levels of free plasminogen in women on oral contraceptives low in oestrogen. Thromb Haemostas 1982; 48: 283-285
    PubMedGoogle Scholar
  • 17 Teger-Nilsson AC, Friberger P, Gyzander E. Determination of a new rapid plasmin inhibitor in human blood by means of a plasmin specific tripeptide substrate. Scand J Clin Lab Invest 1977; 37: 403-409
    CrossrefPubMedGoogle Scholar
  • 18 Gallimore MJ, Amundsen E, Aasen AO, Larsbraaten M, Lyngaas K, Svendsen L. Studies on plasma antiplasmin activity using a new plasmin specific chromogenic tripeptide substrate. Thromb Res 1979; 14: 51-60
    CrossrefPubMedGoogle Scholar
  • 19 Astrup T. Fibrinolysis: An overview. Progress in Chemical Fibrinolysis and Thrombolysis. Davidson JF, Rowan RM, Samama MM, Desnoyers PC. (eds) Raven Press; New York: 1978. pp 1-57
    Google Scholar
  • 20 Astrup T, Jespersen J. Thrombosis, disseminated intravascular coagulation, and the dynamic haemostatic balance. International Angiology. 1983 (in press)
    PubMedGoogle Scholar
  • 21 Brandt P, Stenbjerg S. Subcutaneous heparin for thrombosis in pregnant women with hereditary antithrombin deficiency. Lancet 1979; 1: 100-101
    PubMedGoogle Scholar
  • 22 Jespersen J. Termination of pregnancy in a woman with hereditary antithrombin deficiency under antithrombotic protection with sub-cutaneous heparin and infusion of plasma. Gynecol Obstet Invest 1981; 12: 267-271
    CrossrefPubMedGoogle Scholar
  • 23 Jespersen J, Ingeberg S, Bach E. Antithrombin III and platelets during the normal menstrual cycle and in women receiving oral contraceptives low in oestrogen. Gynecol Obstet Invest 1983; 15: 153-162
    CrossrefPubMedGoogle Scholar
  • 24 Bottiger LE, Boman G, Eklund G, Westerholm B. Oral contraceptives and thromboembolic disease: Effects of lowering oestrogen content. Lancet 1980; 1: 1097-1101
    PubMedGoogle Scholar
  • 25 Jespersen J. A sequential study of plasma euglobulin fibrinolytic activity during the normal menstrual cycle and in women on oral contraceptives low in oestrogen. Gynecol Obstet Invest 1983; 15: 266-274
    CrossrefPubMedGoogle Scholar
  • 26 Jespersen J, Kluft C. Plasma fibrinolytic potential in women on oral contraceptives low in oestrogen. Haemostasis 1982; 12: 37 (abstr)
    PubMedGoogle Scholar
  • 27 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
  • 28 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
  • 29 Gyzander E, Friberger P, Myrwold H, Noppa H, Olsson R, Teger- Nilsson AC, Wallmo L. Antiplasmin determination by means of the plasmin specific substrate S-2251 - methodological studies and some clinical applications. Witt I. (ed) New Methods for the Analysis of Coagulation Using Chromogenic Substrates. Walter de Gruyter; New York: 1977. pp 226-247
    Google Scholar
  • 30 Wallmo L, Gyzander E, Karlsson K, Lindstedt G, Rådberg T, Teger-Nilsson AC. α2-Antiplasmin and α2-macroglobulin - the main inhibitors of fibrinolysis - during the menstrual cycle, pregnancy, delivery and treatment with oral contraceptives. Acta Obstet Gynecol Scand 1982; 61: 417-422
    CrossrefPubMedGoogle Scholar
  • 31 Aoki N. Natural inhibitors of fibrinolysis. Prog Cardiovasc Dis 1979; 21: 267-286
    CrossrefPubMedGoogle Scholar
  • 32 Alkjaersig N, Fletcher A, Burstein R. Association between oral contraceptives use and thromboembolism. A new approach to its identification Am J Obstet Gynecol 1975; 122: 199-209
    CrossrefPubMedGoogle Scholar
  • 33 Howie PW, Mallinson AC, Prentice CR M, Horne CH W, McNicol GP. Effect of combined oestrogen-progesteron oral contraceptives, oestrogen and progesteron on antiplasmin and antithrombin activity. Lancet 1970; 2: 1329-1332
    PubMedGoogle Scholar
  • 34 Adham NF, Wilding P, Mehl J, Hoverbach BJ. α2-Macroglobulin levels in human serum. I. The effect of sex and estrogen. II. The role of α2-macroglobulin as carrier for insulin. J Lab Clin Med 1968; 71: 271-282
    PubMedGoogle Scholar
  • 35 Guagnelli E, Bertolini G, Cappelletti M, Colombo G. Thrombin inhibitors in women on oral contraceptives. Acta Haematol 1981; 65: 205-210
    CrossrefPubMedGoogle Scholar
  • 36 Laursen B, von HerbstT, Ewald EC, Pedersen SC. Antithrombin III and fibrinolysis during pregnancy and oral contraceptives therapy. Ugeskr Laeger 1976; 138: 344-348
    PubMedGoogle Scholar
  • 37 Persson BL, Holmberg L, Åstedt B, Nilsson IM. Coagulation and fibrinolysis in pregnancy complicated by intrauterine growth retardation. Acta Obstet Gynecol Scand 1982; 61: 455-459
    CrossrefPubMedGoogle Scholar
  • 38 Wessler S. Thrombosis and sex hormones: A perplexing liaison. J Lab Clin Med 1980; 96: 757-761
    PubMedGoogle Scholar