Are Haemostatic and Fibrinolytic Parameters Predictors of Preeclampsia in Pregnancy-Associated Hypertension?

Summary

The plasma levels of several haemostatic and fibrinolytic parameters were measured before and after delivery in 61 hypertensive pregnant women of whom 22 developed preeclampsia, and compared to the results obtained in 42 normal pregnant women. In the two last weeks before delivery (D ≤ –15) tPA antigen, PAI-1 activity, vWF: Ag/FVIII: C ratio, ATIII activity and platelet count were found to be significantly different in the hypertensive pregnant women with and without preeclampsia. Combined all together, an association of three of these five parameters were found to be pathological (i.e.: tPA: Ag ≥19 ng/ml, PAI-1 activity ≥58 IU/ml, vWF: Ag/FVIII: C ratio 5≥2.6, ATIII activity ≤73%) in none of the hypertensive women without preeclampsia and in only 35% of the preeclamptic group. A positive correlation was demonstrated between vWF:Ag/FVIII:C ratio and tPA:antigen levels suggesting that both tPA and vWF: Ag could be considered as early indicators of a possible micro angiopathy occurring in preeclampsia. However, due to the high dispersion of the results, it appears that the investigated haemostatic and/or fibrinolytic criteria give only presumptive arguments before assigning risk for preeclampsia development among hypertensive pregnant women.

• References

• 1 Stirling Y, Woolf L, North WRS, Segatchian MJ, Meade TW. Haemostasis in normal pregnancy. Thromb Haemostas 1984; 52: 176-82
• 2 Poller L, Thomson J, Coope J. Conjugated equine oestrogens and blood clotting: a follow-up report. Br Med J 1977; 1: 395-6
• 3 Bonnar J. Haemostasis and coagulation disorders in pregnancy. In: Haemostasis and Thrombosis.. Bloom AL, Thomas DP. (ed) Churchill Livingstone, Edinburgh: 1987. 34 570-84
• 4 Kruithof EKO, Tran-Thang C, Gudinchet A, Hauer J, Nicoloso G, Genton C, Welti H, Bachmann F. Fibrinolysis in pregnancy: a study of plasminogen activator inhibitors. Blood 1987; 69: 460-6
• 5 Wright JG, Cooper P, Åstedt B, Lecander I, Wilde JT, Preston FE, Greaves M. Fibrinolysis during normal human pregnancy: complex inter-relationships between plasma levels of tissue plasminogen activator and inhibitors, and the euglobulin clot lysis time. Br J Haematol 1988; 69: 253-8
• 6 Hughes EC. Obstetric-gynecologic terminology. Davis, Philadelphia, PA: 1972. pp 422-3
• 7 Sundström S, Olsson M, Holmberg PA, Lecander I, Åstedt B, Rånby M. Determination of PAI-1 activity in pregnancy plasma requires the use of single-chain tPA (Abstract). Fibrinolysis 1988; 2 (suppl 1) 35
• 8 Esteliés A, Gilabert J, Aznar J, Loskutoff DJ, Schleef RR. Changes in the plasma levels of type 1 and type 2 plasminogen activator inhibitors in normal pregnancy and in patients with severe preeclampsia. Blood 1989; 74: 1332-8
• 9 Shimada H, Takashima E, Soma M, Murakami M, Maeda Y, Kasakura S, Takada A, Takada Y. Source of increased plasminogen activators during pregnancy and puerperium. Thromb Res 1989; 54: 91-8
• 10 Arias F, Andrinopoulos G, Zamora J. Whole blood fibrinolytic activity in normal and hypertensive pregnancies and its relation to the placental concentration of urokinase inhibitor. Am J Obstet Gynecol 1979; 133: 624-9
• 11 Fletcher AP, Alkjaersig NK, Burstein R. The influence of pregnancy upon blood coagulation and plasma fibrinolytic enzyme function. Am J Obstet Gynecol 1979; 134: 743-51
• 12 Kjaeldgaard A, Pschera H, Larsson B, Gaffney P, Åstedt B. Plasminogen activators and inhibitors in amniotic fluid. Fibrinolysis 1989; 3: 203-6
• 13 Aznar J, Gilabert J, Estellés A, España F. Fibrinolytic activity and protein C in preeclampsia. Thromb Haemostas 1986; 55: 314-7
• 14 Ballegeer V, Kieckens L, Spitz B, van Assche A, Collen D. Plasma levels of fibronectin, plasminogen activator inhibitor 1 and fibrin fragment D-dimer in preeclampsia. Fibrinolysis 1988; (suppl 1) 2: 115 (Abstr 264)
• 15 Jørgensen M, Philips M, Thorsen S, Selmer J, Zeuthen J. Plasminogen activator inhibitor-1 is the primary inhibitor of tissue-type plasminogen activator in pregnancy plasma. Thromb Haemostas 1987; 58: 872-8
• 16 Kluft C, Verheijen JH, Jie AFH, Rijken DC, Preston FE, Sue-Ling HM, Jespersen J, Arsen AO. The post operative fibrinolytic shut down: a rapidly reverting acute phase pattern for the fast-acting inhibitor of tissue-type plasminogen activator after trauma. Scand J Clin Lab Invest 1985; 45: 605
• 17 Bonnar J, Mc Nicol GP, Douglas AS. Coagulation and fibrinolytic systems in preeclampsia and eclampsia. Br Med J 1971; 2: 12-6
• 18 Howie PW, Prentice CWM, Mc Nicol GP. Coagulation, fibrinolysis and platelet function in preeclampsia, essential hypertension and placenta insufficiency. Obstet Gynaecol Br Commonwealth 1971; 78: 992-1003
• 19 Trofatter KF, Howell ML, Greenberg CS, Hage ML. Use of the fibrin D-dimer in screening for coagulation abnormalities in preeclampsia. Obstet Gynecol 1989; 73: 435-40
• 20 Thornton JG, Molloy BJ, Vinall PS, Philips PR, Hughes R, Davies JA. A prospective study of haemostatic tests at 28 weeks gestation as predictors of preeclampsia and growth retardation. Thromb Haemostas 1989; 61: 243-45
• 21 Ballegeer V, Monbaerts P, Declerck PJ, Spitz B, van Assche FA, Collen D. Fibrinolytic response to venous occlusion and fibrin fragment D-dimer levels in normal and complicated pregnancy. Thromb Haemostas 1987; 58: 1030-2
• 22 Redman CWG, Bonnar J, Beilin L. Early platelet consumption in preeclampsia. Br Med J 1978; 1: 467-9
• 23 Inglis TCM, Stuart J, George AJ, Davies AJ. Haemostatic and rheological changes in normal pregnancy and preeclampsia. Br J Haematol 1982; 50: 461-5
• 24 Gilabert J, Fernandez JA, España F, Aznar J, Estellés A. Physiological coagulation inhibitors (Protein S, Protein C and Antithrombin III) in severe preeclamptic states and in users of oral contraceptives. Thromb Res 1988; 49: 319-29
• 25 Friedman KD, Borok Z, Owen J. Heparin cofactor activity and antithrombin III antigen levels in preeclampsia. Thromb Res 1986; 43: 409-16
• 26 Weiner CP, Kwaan HC, Xu C, Paul M, Burmeister L, Hauck W. Antithrombin III activity in women with hypertension during pregnancy. Obstet Gynecol 1985; 65: 301-6
• 27 Weenink GH, Borm JJJ, Ten Cate JW, Treffers PE. Antithrombin III levels in normotensive and hypertensive pregnancy. Gynecol Obstet Invest 1983; 16: 230-42
• 28 Pekonen F, Rasi V, Ammala M, Viinikka L, Ylikorkala O. Platelet function and coagulation in normal and preeclamptic pregnancy. Thromb Res 1986; 43: 553-60
• 29 Thorton CA, Bonnar J. Factor VIII related antigen and factor VIII coagulant activity in normal and preeclamptic pregnancy. Br J Obstet Gynaecol 1977; 84: 919-23
• 30 Brenner B, Zwang E, Bronshtein M, Seligsohn U. Von Willebrand factor multimeric patterns in pregnancy induced hypertension. Thromb Haemostas 1989; 62: 715-7