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; Johannes Sidelmann

doi:10.1055/s-0038-1665260

Thrombosis and Haemostasis, Table of Contents

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

› Author Affiliations

Abstract

PDF Download

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

PDF (482 kb)

References

References
1 Müllertz S, Clemmensen I. The primary inhibitor of plasmin in human plasma. Biochem J 1976; 159: 545-553
2 Collen D. Identification and some properties of a new fast-reacting plasmin inhibitor in human plasma. Eur J Biochem 1976; 69: 209-216
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
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
5 Astrup T. The biological significance of fibrinolysis. Lancet 1956; 3: 565-568
6 Stormorken H. The thrombo-haemorrhagic balance. Acta Med Scand 1980; 642 suppl 131-140
7 Koie K, Kamiya T, Ogata K, Takamatsu J. α₂-Plasmin-inhibitor deficiency (Miyasato disease). Lancet 1978; 2: 1334-1336
8 Kluft C, Vellenga E, Brommer EJ P. Homozygous α₂-antiplasmin deficiency. Lancet 1979; 2: 206
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
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
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
12 Brommer EJ P, Gevers Leuven JA, Kluft C, Wijngaards G. Fibrinolytic inhibitor in type II hyperlipoproteinaemia. Lancet 1982; 2: 1066
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
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
15 Sakata Y, Aoki N. Cross-linking of α₂-antiplasmin inhibitor to fibrin by fibrin-stabilizing factor. J Clin Invest 1980; 65: 290-297
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
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
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
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
20 Astrup T, Jespersen J. Thrombosis, disseminated intravascular coagulation, and the dynamic haemostatic balance. International Angiology. 1983 (in press)
21 Brandt P, Stenbjerg S. Subcutaneous heparin for thrombosis in pregnant women with hereditary antithrombin deficiency. Lancet 1979; 1: 100-101
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
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
24 Bottiger LE, Boman G, Eklund G, Westerholm B. Oral contraceptives and thromboembolic disease: Effects of lowering oestrogen content. Lancet 1980; 1: 1097-1101
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
26 Jespersen J, Kluft C. Plasma fibrinolytic potential in women on oral contraceptives low in oestrogen. Haemostasis 1982; 12: 37 (abstr)
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
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
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
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
31 Aoki N. Natural inhibitors of fibrinolysis. Prog Cardiovasc Dis 1979; 21: 267-286
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
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
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
35 Guagnelli E, Bertolini G, Cappelletti M, Colombo G. Thrombin inhibitors in women on oral contraceptives. Acta Haematol 1981; 65: 205-210
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
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
38 Wessler S. Thrombosis and sex hormones: A perplexing liaison. J Lab Clin Med 1980; 96: 757-761