Download PDF
Thromb Haemost 1991; 65(02): 134-138
DOI: 10.1055/s-0038-1647471
Original Article
Schattauer GmbH Stuttgart

C1-Esterase Inhibitor in Uncomplicated Pregnancy and Mild and Moderate Preeclampsia

Walter-Michael Halbmayer
1   The Central Laboratory, Municipal Hospital of the City of Vienna-Lainz, Vienna, Austria
,
Pierre Hopmeier
1   The Central Laboratory, Municipal Hospital of the City of Vienna-Lainz, Vienna, Austria
,
Christine Mannhalter
2   The First Department of Medicine, University of Vienna, School of Medicine, Vienna, Austria
,
Friedrich Heuss
1   The Central Laboratory, Municipal Hospital of the City of Vienna-Lainz, Vienna, Austria
,
Sepp Leodolter
3   Department of Obstetrics and Gynecology, Municipal Hospital of the City of Vienna-Lainz, Vienna, Austria
,
Karl Rubi
4   The Central Laboratory, Kaiserin Elisabeth Hospital, Vienna, Austria
,
Michaet Fischer
1   The Central Laboratory, Municipal Hospital of the City of Vienna-Lainz, Vienna, Austria
› Author Affiliations
Further Information

Publication History

Received: 24 November 1989

Accepted after revision 04 October 1990

Publication Date:
24 July 2018 (online)

  PDF Download  Permissions and Reprints

Summary

Routine coagulation tests and measurement of the plasma levels of C1-esterase inhibitor (C1-INH) and antithrombin III were performed in 17 women with mild preeclampsia, 10 women with moderate preeclampsia and 20 women with uncomplicated pregnancy. All pregnant probands were within the third trimester of pregnancy. 20 non-pregnant women were used as controls. The gfoups were matched in age and the pregnant ones were also matched in gestational age.

C1-INH activity and antigen were significantly reduced (p <0.002) in normally pregnant women as compared with nonpregnant ones. Further, CI-INH activity was lower in women with mild preeclampsia and significantly lower in women with moderate preeclampsia (p <0.05) as compared with normally pregnant women. None of the plasmatic coagulation tests was indicative of a consumption reaction. We conclude that C1-INH activity and antigen reductions are commonly associated with pregnancy. Furthermore, as markedly lower values can be found in mild and moderate preeclampsia, measurement of the C1-INH activity in pregnant women within the third trimester might proof useful to establish the diagnosis of a preeclamptic condition.

 

  • References

  • 1 Inglis TCM, Stuart J, George AJ, Davies AJ. Haemostatic and rheological changes in normal pregnancy and pre-eclampsia. Br J Haematol 1982; 50: 461-465
    CrossrefPubMedGoogle Scholar
  • 2 Condie RG, Ogston D. Sequential studies on components of the haemostatic mechanism in pregnancy with particular reference to the development of pre-eclampsia. Br J Obstet Gynaecol 1967; 83: 938-942
    PubMedGoogle Scholar
  • 3 Hellgren M, Blomback M. Studies on blood coagulation and fibrinolysis in pregnancy, during delivery and in the puerperium. I. Normal condition. Gynecol Obstet Invest 1981; 12: 141-154
    PubMedGoogle Scholar
  • 4 Stirling Y, Woolf L, North WRS, Seghatchian MJ, Meade TW. Haemostasis in normal pregnancy. Thromb Haemostas 1984; 52 (02) 176-182
    PubMedGoogle Scholar
  • 5 Estelles A, Gilabert J, Espana F, Aznar J, Gomez-Lechon MJ. Fibrinolysis in pre-eclampsia. J Fibrinolysis 1987; 1: 209-214
    PubMedGoogle Scholar
  • 6 Aznar J, Gilabert J, Estelles A, Espana F. Fibrinolytic activity and protein C in preeclampsia. Thromb Haemostas 1986; 55 (03) 314-317
    PubMedGoogle Scholar
  • 7 Gaffney PJ, Creighton LJ, Callus M, Thorpe R. Monoclonal antibodies to crosslinked fibrin degradation products (XL-FDP). II. Evaluation in a variety of clinical conditions. Br J Haematol 1988; 68 (01) 91-96
    PubMedGoogle Scholar
  • 8 Borok Z, Weitz J, Owen J, Auerbach M, Nossel HL. Fibrinogen proteolysis and platelet alpha-granule release in preeclampsia/eclampsia. Blood 1984; 63 (03) 525-531
    PubMedGoogle Scholar
  • 9 Hopmeier P, Halbmayer M, Schwarz HP, Heuss F, Fischer M. Protein C and protein S in mild and moderate preeclampsia. Thromb Haemostas 1987; 58 (02) 794-795
    PubMedGoogle Scholar
  • 10 Gow L, Campbell DM, Ogston D. Blood levels of proteinase inhibitors in pre-eclampsia. Br J Obstet Gynaecol 1983; 90: 950-952
    CrossrefPubMedGoogle Scholar
  • 11 Armstrong NPI, Teisner B, Redman CWG, Westergaard JG, Folkersen J, Grudzinskas JG. Complement activation, circulating protease inhibitors and pregnancy-associated proteins in severe preeclampsia. Br J Obstet Gynaecol 1986; 93: 811-814
    CrossrefPubMedGoogle Scholar
  • 12 Hustin J, Foldart JM, Lambotte R. Maternal vascular lesions in preeclampsia and intrauterine growth retardation: light microscopy and immunfluorescence. Obstet Gynecol Surv 1985; 40: 145-149
    CrossrefPubMedGoogle Scholar
  • 13 Holzner JH. Pathology of the placenta in gestosis. In: Dilemmas in Gestosis Janisch H, Reinold E. (eds). Thieme; Stuttgart: 1983: 82-87
  • 14 Weenink GH, Treffers PE, Vijn P, Smorenberg-Schoorl ME, Ten Cate JW. Antithrombin III levels in preeclampsia correlate with maternal and fetal morbidity. Am J Obstet Gynecol 1984; 148: 1092-1097
    CrossrefPubMedGoogle Scholar
  • 15 Trofatter Jr KF, Howell ML, Greenberg CS, Hage ML. Use of the fibrin D-dimer in screening for coagulation abnormalities in preeclampsia. Obstet Gynecol 1989; 73: 435-440
    PubMedGoogle Scholar
  • 16 Kobayashi T, Terao T. Preeclampsia as chronic disseminated intravas-cular coagulation. Study of two parameters: thrombin-antithrombin III complex and D-dimers. Gynecol Obstet Invest 1987; 24 (03) 170-178
    PubMedGoogle Scholar
  • 17 Forbes CD, Pensky J, Ratnoff OD. Inhibition of activated Hageman factor and activated plasma thromboplastin antecedent by purified serum Cl inactivator. J Lab Clin Med 1970; 76: 809-815
    PubMedGoogle Scholar
  • 18 Schreiber AD, Kaplan AP, Austen KF. Inhibition by C1-INH of Hageman factor fragment activation of coagulation, fibrinolysis, and kinin generation. J Clin Invest 1973; 52: 1402-1409
    CrossrefPubMedGoogle Scholar
  • 19 Pixley RA, Schmaier A, Colman RW. Effect of negatively charged activating compounds on inactivation of factor XIIa by C1 inhibitor. Arch Biochem Biophys 1987; 256 (02) 490-498
    CrossrefPubMedGoogle Scholar
  • 20 Lammle B, Berrettini M, Griffin JH. Immunoblotting studies of coagulation factor XII, plasma prekallikrein, and high molecular weight kininogen. Semin Thromb Hemostas 1987; 13 (01) 106-114
    Article in Thieme ConnectPubMedGoogle Scholar
  • 21 Goecke C, Schwabe G. Vorschlag einer Stadieneinteilung der Gestose. Zbl Gyn 1965; 42: 1439
    PubMedGoogle Scholar
  • 22 Kemeter P, Friedrich F. Die Endokrinologie der Schwangerschaft. In: Klinik der Frauenheilkunde und Geburtshilfe. Vol. I. Doderlein G, Wulf KH. (eds). Urban and Schwarzenberg, Munich 1977; Addendum: 1978: 219-60/31
  • 23 Mancini G, Carbonara AT, Heremans JF. Immunochemical quantitation of antigens by single radial immunodiffusion. Immunochemistry 1965; 2: 235-238
    CrossrefPubMedGoogle Scholar
  • 24 Clauss A. Gerinnungsphysiologische Schnellmethode zur Bestim-mung des Fibrinogens. Acta Haematol 1957; 17: 237-246
    CrossrefPubMedGoogle Scholar
  • 25 Harpel PC. Blood proteolytic enzyme inhibitors: Their role in modulating blood coagulation and fibrinolytic enzyme pathways. In: Haemostasis and Thrombosis-Basic Principles and Clinical Practice Colman RW, Hirsh J, Marder VJ, Salzman EW. (eds). JB Lippincott Comp; Philadelphia, PA: 1982: 738
  • 26 Holm S. A simple sequentially rejective multiple test procedure. Scand J Statist 1979; 6: 65-70
    PubMedGoogle Scholar
  • 27 Nowotny Ch, Thaler E, Lechner K, Altmann P. Changes of coagulation in gestosis. In: Dilemmas in Gestosis Janisch H, Reinold E. (eds). Thieme; Stuttgart: 1983: 117-120
  • 28 Schmaier AH, Schapira M, Colman RW. Methods to study the proteins of the contact phase of coagulation. Methods Haematol 1983; 7: 24-47
    PubMedGoogle Scholar
  • 29 Gigli J, Mason JW, Colman RW, Austen KF. Interaction of plasma kallikrein with Cl inhibitor. J Immunol 1970; 104 (03) 574-581
    PubMedGoogle Scholar
  • 30 Nilsson T. On the interaction between human plasma kallikrein and C1-esterase inhibitor. Thromb Haemostas 1983; 49 (03) 193-195
    PubMedGoogle Scholar
  • 31 Lewis GP. Kinins in inflammation and tissue injury. In: Handbook of Experimental Pharmacology. In: Erdos EG. (ed). Springer-Verlag; New York: 1970: 516-530
  • 32 Derkx FHM, Schalekamp MPA, Bouma B, Kluft C, Schalekamp MADH. Plasam kallikrein-mediated activation of the renin-angio-tensin system does not require prior acidification of prorenin. J Clin Endocrinol Metab 1982; 54: 343-348
    CrossrefPubMedGoogle Scholar
  • 33 Nuijens JH, Huijbregts CCM, Eerenberg-Belmer AJM, Abbink JJ, Strack van Schijndel RJM, Felt-Bersma RJF, Thijs LG, Hack CE. Quantification of plasma factor XIIa-C1-inhibitor and kallikrein-C1-inhibitor complexes in sepsis. Blood 1988; 72 (06) 1841-1848
    PubMedGoogle Scholar
  • 34 Stirrat GM, Redman CWG, Levinsky RJ. Circulating immuncom-plexes in pre-eclampsia. Br Med J 1987; 1: 1450-1451
    PubMedGoogle Scholar
  • 35 Petrucco OM. Immunofluorescent studies in renal biopsies in preeclampsia. Br Med J 1974; i 473
    PubMedGoogle Scholar
  • 36 Arias F, Mancilla-Jiminez R. Hepatic fibrinogen deposits in preeclampsia. N Engl J Med 1976; 295: 578
    CrossrefPubMedGoogle Scholar
  • 37 Kitzmiller JL, Benirschke K. Immuno-fluorescent study of placental bed vessels in preeclampsia of pregnancy. Am J Obstet Gynecol 1973; 115: 248
    CrossrefPubMedGoogle Scholar
  • 38 Faulk WP, Jeanet N, Creighton WD, Carbonara A. Immunological studies of the human placenta. J Clin Invest 1974; 54: 1011-1017
    CrossrefPubMedGoogle Scholar
  • 39 Massobrio M, Benedetto C, Bertini E, Tetta C, Camussi G. Immune complexes in preeclampsia and normal pregnancy. Am J Obstet Gynecol 1985; 152: 578-583
    CrossrefPubMedGoogle Scholar
  • 40 Bartl W, Riss P, Knapp W. Evaluation and the prognostic value of freely circulating immune complexes in EPH-gestosis. In: Dilemmas in Gestosis Janisch H, Reinold E. (eds). Thieme; Stuttgart: 1983: 68-71
  • 41 Howert-de-Jong MH, Te Velde ER, Nefkens MJJ, Schuurman HJ. Immune complexes in skin of patients with pre-eclamptic toxaemia. Lancet 1982; ii 387
    PubMedGoogle Scholar
  • 42 Schena FP, Selvaggi L, Pastore A, Germinario C, Loverro G, Bettocchi S. The role if immune complexes (IC) in EPH-gestosis. A dilemma in gestosis. In: Dilemmas in Gestosis Janisch H, Reinold E. (eds). Thieme; Stuttgart: 1983: 65-66
  • 43 Gleicher N, Theofiopopoulos AN, Bears P. Immune complexes in pregnancy. Lancet 1978; i 1108
    PubMedGoogle Scholar
  • 44 Knox GE, Stagno S, Volanakis JE, Huddleston JF. A search for antigen-antibody complexes in pre-eclampsia: Further evidence against immunologic pathogenesis. Am J Obstet Gynecol 1978; 132: 87-89
    CrossrefPubMedGoogle Scholar
  • 45 Balasch J, Mirapeix E, Borche L, Vives J, Gonzales-Merlo J. Further evidence against preeclampsia as an immune complex disease. Obstet Gynecol 1981; 55: 435-437
    PubMedGoogle Scholar
  • 46 Westergaard JG, Svehag S-E, Hau J, Teisner B. Quantitative comparison of circulating immune complexes in normal pregnancy and pregnancy related hypertension. Acta Obstet Gynecol Scand 1986; 65: 181-182
    CrossrefPubMedGoogle Scholar
  • 47 Jespersen J, Kluft C. Increased euglobulin fibrinolytic potential in women on oral contraceptives low in oestrogen-levels of extrinsic and intrinsic plasminogen activators, prekallikrein, factor XII, and Cl-inactivator. Thromb Haemostas 1985; 54 (02) 454-459
    PubMedGoogle Scholar
  • 48 Gordon EM, Ratnoff OD, Saito H, Donaldson VH, Pensky J, Jones PK. Rapid fibrinolysis, augmented Hageman factor (factor XII) titers, and decreased Cl esterase inhibitor titers in women taking oral contraceptives. J Lab Clin Med 1980; 96 (03) 762-769
    PubMedGoogle Scholar
  • 49 Bockers M, Bork K. Kontrazeption und Schwangerschaft beim hereditaren Angioodem. DMW 1987; 112 (13) 507-509
    Article in Thieme ConnectPubMedGoogle Scholar
  • 50 Tietz NW, Saunders WB. (eds). Textbook of Clinical Chemistry. 1986
    PubMedGoogle Scholar
  • 51 Cohen SH, Koethe SM, Kozin F, Rodey G, Arkins JA, Fink JN. Acquired angioedema associated with rectal carcinoma and its response to danazol therapy. J Allergy Clin Immunol 1978; 62: 217-221
    CrossrefPubMedGoogle Scholar
  • 52 Frigas E. Angioedema with acquired deficiency of the Cl inhibitor: A constellation of syndromes. Mayo Clin Proc 1989; 64: 1269-1275
    CrossrefPubMedGoogle Scholar
  • 53 Falus A, Feher KG, Walcz E, Brozik M, Fust G, Hidvegi T, Feher T, Meretey K. Hormonal regulation of complement biosynthesis in human cell lines I. Androgens and gamma interferon stimulate the biosynthesis and gene expression of Cl inhibitor in human cell lines U937 and HEPG2. Mol Immunol 1990; 27 (02) 191-196
    PubMedGoogle Scholar
  • 54 Schiff E, Peleg E, Goldenberg M, Rosenthal T, Ruppin E, Tamarkin M, Barkai G, Ben-Baruch G, Yahal I, Blankstein J, Goldman B, Mashiach S. The use of aspirin to prevent pregnancy-induced hypertension and lower the ratio of thromboxane A2 to prostacyclin in relatively high risk pregnancies. N Engl J Med 1989; 321 (06) 351-356
    CrossrefPubMedGoogle Scholar
  • 55 Benigni A, Gregorini G, Frusca T, Chiabrando C, Ballerini S, Valcamonico A, Orisio S, Piccinelli A, Pinciroli V, Fanelli R, Gastaldi A, Remuzzi G. Effect of low-dose aspirin on fetal and maternal generation of thromboxane by platelets in women at risk for pregnancy-induced hypertension. N Engl J Med 1989; 321 (06) 357-362
    CrossrefPubMedGoogle Scholar
  • 56 Rao AK, Schapira M, Niewiarowski S, Budzynski A, Schmaier A, Mills D, Willis J, Beckett C, James A, Silver L, Scott C, James P, Harris M, Kieve C, Clements ML, Levine M, Hughes T, Black R, Colman RW. Prospective study of hemostatic systems during mild Rocky Mountain spotted fever. Clin Res 1982; 30: 328A
    PubMedGoogle Scholar
  • 57 Yamada T, Harber P, Pettit GW, Wing DA, Oster CN. Activation of the kallikrein-kinin system in Rocky Mountain spotted fever. Ann Intern Med 1978; 88: 764-768
    CrossrefPubMedGoogle Scholar
  • 580 Colman RW, Edelman R, Scott CF, Gilman RH. Plasma kallikrein activation and inhibition during typhoid fever. J Clin Invest 1978; 61: 287-296
    CrossrefPubMedGoogle Scholar
  • 59 Mason JW, Kleeberg U, Dolan P, Colman RW. Plasma kallikrein and Hageman factor in gram-negative bacteremia. Ann Intern Med 1970; 73: 545-551
    CrossrefPubMedGoogle Scholar
  • 60 O’Donnell Jr TF, Clowes Jr GHA, Colman RW. Kinin activation in the blood of patients with sepsis. Surg Gynecol Obstet 1976; 143: 539-545
    PubMedGoogle Scholar
  • 61 Carvalho AC, Colman RW, Lees RS. Platelet function in hyperlipoproteinemia. N Engl J Med 1974; 290: 434-438
    CrossrefPubMedGoogle Scholar
  • 62 Carvalho AC, Lees RS, Vaillancourt RA, Colman RW. Effect of clofibrate on intravascular coagulation in hyperlipoproteinemia. Circulation 1977; 56: 114-118
    CrossrefPubMedGoogle Scholar
  • 63 Lange LG, Carvalho AC, Bagdasarian A, Lahiri B, Colman RW. Activation of Hageman factor in the nephrotic syndrome. Am J Med 1974; 56: 565-569
    CrossrefPubMedGoogle Scholar
  • 64 Kallen RJ, Soo-Kwang L. A study of the plasma kinin-generating system in children with the minimal lesion, idiopathic nephrotic syndrome. Pediatr Res 1975; 9: 705-709
    CrossrefPubMedGoogle Scholar
  • 65 Wong PY, Talamo RC, Babior BM, Raymond GG, Colman RW. Kallikrein-kinin system in postgastrectomy dumping syndrome. Ann Intern Med 1974; 80: 577-581
    CrossrefPubMedGoogle Scholar
  • 66 Mason JW, Colman RW. The role of Hageman factor in disseminated intravascular coagulation induced by sepsis, neoplasia or liver disease. Thromb Diath Haemorrh 1971; 26: 325-331
    PubMedGoogle Scholar
  • 67 Philapitsch A, Murday H, Popov-Cenic S. Das Kallikreinsystem: Aktivierungs- und Inhibitionspotential wahrend des extrakorporalen Kreislaufes in einer Placebo-Aprotinin-Cl-Inhibitor-Studie. In: Pro-teolyse und Proteinaseninhibition in der Herz- und GefaBchirurgie Dudziak R, Kirchhoff PG, Reuter HD, Schumann F. (eds). Schattauer, Stuttgart: 1985: 201-208
  • 68 Hentges F, Humbel R, Dicato M, Hemmer R, Kuntziger H. Acquired Cl esterase-inhibitor deficiency: Case report with emphasis on complement and kallikrein activation during two patterns of clinical manifestations. J Allergy Clin Immunol 1986; 78: 860-867
    CrossrefPubMedGoogle Scholar
  • 69 Rodriguez M, Ancochea J, De Buen C, Merino JL, Marques G, Vivanco F. Acquired Cl-inhibitor deficiency associated with a lupuslike anticoagulant activity. Ann Allergy 1988; 61: 348-350
    PubMedGoogle Scholar
  • 70 Jackson J, Feighery C. Autoantibody-mediated acquired deficiency of Cl inhibitor. N Engl J Med 1988; 318: 122-123
    CrossrefPubMedGoogle Scholar
  • 71 Jackson J, Sim RB, Whelan A, Feighery C. An IgG autoantibody which inactivates Cl-inhibitor. Nature 1986; 323: 722-724
    CrossrefPubMedGoogle Scholar
  • 72 Alsenz J, Bork K, Loos M. Autoantibody-mediated acquired deficiency of Cl inhibitor. N Engl J Med 1986; 316: 1360-1366
    PubMedGoogle Scholar
  • 73 Pascual M, Widman J-J, Schifferli JA. Recurrent febrile panniculitis and hepatitis in two patients with acquired complement deficiency and paraproteinemia. Am J Med 1987; 83: 959-962
    CrossrefPubMedGoogle Scholar
  • 74 Gelfand JA, Boss GR, Lockard ConleyC, Reinhart R, Frank MM. Acquired Cl esterase inhibitor deficiency and angioedema: A review. Annu Rev Med 1979; 58 (04) 321-328
    PubMedGoogle Scholar
  • 75 Rosen FS, Alper CA, Pensky J, Klemperer MR, Donaldson VH. Genetically determined herterogeneity of the Cl esterase inhibitor in patients with hereditary angioneurotic edema. J Clin Invest 1971; 50: 2143-2149
    CrossrefPubMedGoogle Scholar
  • 76 Donaldson VH, Harrison RA, Rosen FS, Bing DH, Kindness G, Canar J, Wagner CJ, Awad S. Variability in purified dysfunctional Cl-inhibitor proteins from patients with hereditary angioneurotic edema. Functional and analytical gel studies. J Clin Invest 1985; 75: 124-132
    PubMedGoogle Scholar