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Increased fibrinolytic activity during use of oral contraceptives is counteracted by an enhanced factor XI-independent down regulation of fibrinolysis: a randomized cross-over study of two low-dose oral contraceptives.
Thromb Haemost. 2000 Jul; 84(1):9-14.TH

Abstract

The effect of oral contraceptives (OC) on fibrinolytic parameters was investigated in a cycle-controlled cross-over study in which 28 non-OC using women were randomly prescribed either a representative of the so-called second (30 microg ethinylestradiol, 150 microg levonorgestrel) or third generation OC (30 microg ethinylestradiol, 150 microg desogestrel) and who switched OC after a two month wash out period. During the use of OC, the levels of tissue-type plasminogen activator (tPA) activity, plasminogen, plasmin-alpha2-antiplasmin complexes and D-dimer significantly increased (by 30 to 80%), while the levels of plasminogen activator inhibitor- (PAI-1) antigen, PAI-1 activity and tPA antigen significantly decreased (25 to 50%), suggesting an increase in endogenous fibrinolytic activity. These OC-induced changes were not different between the two contraceptive pills. TAFI (thrombin-activatable fibrinolysis inhibitor) levels increased on levonorgestrel, and even further increased on desogestrel. A clot lysis assay that probes both fibrinolytic activity and the efficacy of the coagulation system to generate thrombin necessary to down regulate fibrinolysis via TAFI showed no change of the clot lysis time during OC use. This finding suggests that the OC-induced increase in endogenous fibrinolytic activity is counteracted by an increased capacity of the coagulation system to down regulate fibrinolysis via TAFI. Indeed we observed that during OC use there was a significant increase of F1+2 generation during clot formation. When these assays were performed in the presence of an antibody against factor XI, we observed that the clot lysis time was significantly increased during OC use and that the increase in F1+2 generation during OC therapy was due to a factor XI-independent process, which was significantly higher on desogestrel than on levonorgestrel. These data indicate that the OC-induced inhibition of endogenous fibrinolysis takes place in a factor XI-independent way and is more pronounced on desogestrel than on levonorgestrel-containing OC.

Authors+Show Affiliations

Department of Haematology, University Medical Center Utrecht, The Netherlands. j.c.meijers@amc.uva.nlNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Comparative Study
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

10928462

Citation

Meijers, J C., et al. "Increased Fibrinolytic Activity During Use of Oral Contraceptives Is Counteracted By an Enhanced Factor XI-independent Down Regulation of Fibrinolysis: a Randomized Cross-over Study of Two Low-dose Oral Contraceptives." Thrombosis and Haemostasis, vol. 84, no. 1, 2000, pp. 9-14.
Meijers JC, Middeldorp S, Tekelenburg W, et al. Increased fibrinolytic activity during use of oral contraceptives is counteracted by an enhanced factor XI-independent down regulation of fibrinolysis: a randomized cross-over study of two low-dose oral contraceptives. Thromb Haemost. 2000;84(1):9-14.
Meijers, J. C., Middeldorp, S., Tekelenburg, W., van den Ende, A. E., Tans, G., Prins, M. H., Rosing, J., Büller, H. R., & Bouma, B. N. (2000). Increased fibrinolytic activity during use of oral contraceptives is counteracted by an enhanced factor XI-independent down regulation of fibrinolysis: a randomized cross-over study of two low-dose oral contraceptives. Thrombosis and Haemostasis, 84(1), 9-14.
Meijers JC, et al. Increased Fibrinolytic Activity During Use of Oral Contraceptives Is Counteracted By an Enhanced Factor XI-independent Down Regulation of Fibrinolysis: a Randomized Cross-over Study of Two Low-dose Oral Contraceptives. Thromb Haemost. 2000;84(1):9-14. PubMed PMID: 10928462.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Increased fibrinolytic activity during use of oral contraceptives is counteracted by an enhanced factor XI-independent down regulation of fibrinolysis: a randomized cross-over study of two low-dose oral contraceptives. AU - Meijers,J C, AU - Middeldorp,S, AU - Tekelenburg,W, AU - van den Ende,A E, AU - Tans,G, AU - Prins,M H, AU - Rosing,J, AU - Büller,H R, AU - Bouma,B N, PY - 2000/8/6/pubmed PY - 2001/3/3/medline PY - 2000/8/6/entrez SP - 9 EP - 14 JF - Thrombosis and haemostasis JO - Thromb Haemost VL - 84 IS - 1 N2 - The effect of oral contraceptives (OC) on fibrinolytic parameters was investigated in a cycle-controlled cross-over study in which 28 non-OC using women were randomly prescribed either a representative of the so-called second (30 microg ethinylestradiol, 150 microg levonorgestrel) or third generation OC (30 microg ethinylestradiol, 150 microg desogestrel) and who switched OC after a two month wash out period. During the use of OC, the levels of tissue-type plasminogen activator (tPA) activity, plasminogen, plasmin-alpha2-antiplasmin complexes and D-dimer significantly increased (by 30 to 80%), while the levels of plasminogen activator inhibitor- (PAI-1) antigen, PAI-1 activity and tPA antigen significantly decreased (25 to 50%), suggesting an increase in endogenous fibrinolytic activity. These OC-induced changes were not different between the two contraceptive pills. TAFI (thrombin-activatable fibrinolysis inhibitor) levels increased on levonorgestrel, and even further increased on desogestrel. A clot lysis assay that probes both fibrinolytic activity and the efficacy of the coagulation system to generate thrombin necessary to down regulate fibrinolysis via TAFI showed no change of the clot lysis time during OC use. This finding suggests that the OC-induced increase in endogenous fibrinolytic activity is counteracted by an increased capacity of the coagulation system to down regulate fibrinolysis via TAFI. Indeed we observed that during OC use there was a significant increase of F1+2 generation during clot formation. When these assays were performed in the presence of an antibody against factor XI, we observed that the clot lysis time was significantly increased during OC use and that the increase in F1+2 generation during OC therapy was due to a factor XI-independent process, which was significantly higher on desogestrel than on levonorgestrel. These data indicate that the OC-induced inhibition of endogenous fibrinolysis takes place in a factor XI-independent way and is more pronounced on desogestrel than on levonorgestrel-containing OC. SN - 0340-6245 UR - https://www.unboundmedicine.com/medline/citation/10928462/Increased_fibrinolytic_activity_during_use_of_oral_contraceptives_is_counteracted_by_an_enhanced_factor_XI_independent_down_regulation_of_fibrinolysis:_a_randomized_cross_over_study_of_two_low_dose_oral_contraceptives_ DB - PRIME DP - Unbound Medicine ER -