Fibrinolytic Response to Venous Occlusion and Fibrin Fragment D-Dimer Levels in Normal and Complicated Pregnancy

Summary

The fibrinolytic response to venous occlusion was assessed in 29 women with normal or complicated pregnancy, by measurements of total t-PA and free t-PA with specific ELISAs. The release of t-PA from the vessel wall was 11±9 ng/ml in nonpregnant women (mean ± SD, n = 6) but was markedly reduced throughout pregnancy. Following venous occlusion, free t-PA increased by 12 ± 11 ng/ml in non-pregnant women but remained below the detection limit of 2 ng/ml towards the end of pregnancy. A markedly reduced t-PA release with absence of free t-PA was also observed during late pregnancy in patients with insulin-dependent diabetes mellitus, intra-uterine growth ietaida-tion and pre-eclampsia.

Plasma levels of fragment D-dimer of cross-linked fibrin were measured with a specific FITS A in 79 pregnant women. D-dimer levels were 129 ± 36 ng/ml (mean ± SD, n = 8) in non-pregnant women and increased to 400 ± 170 ng/ml (n = 25) and 440 ± 220 ng/ml (n – 22) during the second and third trimester of pregnancy respectively. Significantly higher levels than observed in uncomplicated third trimester pregnancies were found in 3 out of 6 diabetic and in 2 out of 7 pre-eclamptic women.

It is concluded that the t-PA release after venous occlusion is significantly reduced during pregnancy. In addition, released t-PA is rapidly inhibited. The levels of fragment D-dimer increase during pregnancy, suggesting that, notwithstanding the marked impairment of the fibrinolytic response to venous occlusion, the fibrinolytic system remains functionally active.

Keywords

Fibrinolysis - Tissue-type plasminogen activator (t-PA) - Fibrin fragment D-dimer - Pregnancy - Venous occlusion

• References

• 1 Biezmski JJ, Moore HC. Fibrinolysis in normal pregnancy. J Clin Pathol 1958; 11: 306-310
• 2 Brakman P. The fibrinolytic system in human blood during pregnancy. Am J Obstet Gynecol 1966; 94: 14-20
• 3 Bonnar J, McNicol GP, Douglas AS. Fibrinolytic enzyme system and pregnancy. Br Med J 1969; 3: 387-389
• 4 Thorsen S. The inhibition of tissue plasminogen activator and urokinase-induced fibrinolysis by some natural proteinase inhibitors and by plasma and serum from normal and pregnant subjects. Scand J Clin Lab Invest 1973; 31: 51-59
• 5 Walker JE, Gow L, Campbell DM, Ogston D. The inhibition by plasma of urokinase and tissue activator-induced fibrinolysis in pregnancy and the puerperium. Thromb Haemostas 1983; 49: 21-23
• 6 Kruithof E KO, Tran-Thang C, Gudinchet A, Hauert J, Nicoloso G, Genton C, Welti H, Bachmann F. Fibrinolysis in pregnancy: a study of plasminogen activator inhibitors. Blood 1987; 69: 460-466
• 7 Holvoet P, Boes J, Collen D. Measurement of free one-chain tissue-type plasminogen activator in human plasma with an enzyme-linked immunosorbent assay based on an active site-specific murine monoclonal antibody. Blood 1987; 69: 284-289
• 8 Declerck PJ, Mombaerts P, Holvoet P, De Mol M, Collen D. Fibrinolytic response and fibrin fragment D-dimer levels in patients with deep vein thrombosis. Thromb Haemostas 1987; 58: 1024-1029
• 9 Pritchard JA, MacDonald PC, Gant NF. Hypertensive disorders in pregnancy. In: Williams Obstetrics. 17th edition. Appleton-Century-Crofts, Norwalk Conn. 1985: 525-560
• 10 Stubbs T, Lazarchick J, Horger III EO. Plasma fibronectin levels in preeclampsia: a possible biochemical marker for vascular endothelial damage. Am J Obstet Gynecol 1984; 150: 885-887
• 11 Holvoet P, Cleemput H, Collen D. Assay of human tissue-type plasminogen activator (t-PA) with an enzyme-linked immunosorbent assay (ELISA) based on three murine monoclonal antibodies to t-PA. Thromb Haemostas 1985; 54: 684-687
• 12 Isacson S, Nilsson IM. Defective fibrinolysis in blood and vein walls in recurrent idiopathic venous thrombosis. Acta Chir Scand 1972; 138: 313-319
• 13 Nilsson IM, Ljungner H, Tengborn L. Two different mechanisms in patients with venous thrombosis and defective fibrinolysis: low concentration of plasminogen activator or increased concentration of plasminogen activator inhibitor. Br Med J 1985; 290: 1453-1455
• 14 Juhan-Vague I, Valadier J, Alessi MC, Aillaud MF, Ansaldi J, Philip-Joet C, Holvoet P, Serradimigni A, Collen D. Deficient t-PA release and elevated PA inhibitor levels in patients with spontaneous or recurrent deep vein thrombosis. Thromb Haemostas 1987; 57: 67-72
• 15 Nilsson IM, Kullander S. Coagulation and fibrinolytic studies during pregnancy. Act Obstet Gynecol Scand 1967; 46: 273-285
• 16 Yoshimura T, Yamashita J, Ito M, Matsui K, Maeyama M. Placental plasminogen activator activity in preeclampsia. Int J Gynaecol Obstet 1985; 23: 311-314
• 17 Robertson WB, Brosens I, Dixon HG. The pathological response of the vessels of the placental bed to hypertensive pregnancy. J Path Bact 1967; 93: 581-592