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Changes in haemostatic parameters during the menstrual cycle and subsequent use of drospirenone-containing oral contraceptives.

AbstractINTRODUCTION:
Oral contraceptives (OC) increase the risk of venous thromboembolism that depends on the OC formulation and could at least partially be explained by impaired function of the protein C-system (APC resistance) and the tissue factor pathway inhibitor (TFPI)-system. There is limited information available on the effects of OC, containing a newer progestogen- drospirenone (DRSP-OC) on these two major anticoagulant pathways, thrombin generation, reflecting the overall state of coagulation, and other coagulation parameters.
METHODS:
In a study population consisting of 14 healthy women (age 21-33 years) we investigated the effect of the menstrual cycle and subsequent use of DRSP-OC on APC resistance, the function of the TFPI-system, thrombin generation and on their major determinants, i.e. prothrombin, antithrombin, FV, FX, FVIII, protein C, protein S(total and free) and TFPI(full-length and free).
RESULTS:
All studied parameters remained unchanged during the menstrual cycle. During DRSP-OC use we observed a significant increase in APC resistance (~2.4-fold), thrombin generation measured at low (~2.2-fold) and high tissue factor concentrations (~1.4-fold), plasma concentrations of prothrombin (19%), FX (31%), FVIII (17%) and protein C (43%). DRSP-OC use impaired the function of the TFPI-system and decreased plasma levels of antithrombin (-6%), FV (-22%), protein Stotal (-21%), protein Sfree (-20%), TFPIfull-length (-36%) and TFPIfree (-46%).
CONCLUSIONS:
DRSP-OC caused procoagulant changes in all studied haemostatic parameters. The impairment of the protein C- and TFPI-systems was more pronounced than the impairment of the coagulation pathways and can at least partially account for the increased risk of venous thromboembolism in users of DRSP-OC.
AuthorsS N Tchaikovski, M C L G D Thomassen, S D Costa, K Bremme, J Rosing
JournalThrombosis research (Thromb Res) Vol. 134 Issue 5 Pg. 1032-7 (Nov 2014) ISSN: 1879-2472 [Electronic] United States
PMID25260941 (Publication Type: Journal Article)
CopyrightCopyright © 2014 Elsevier Ltd. All rights reserved.
Chemical References
  • Androstenes
  • Contraceptives, Oral
  • Lipoproteins
  • Protein S
  • lipoprotein-associated coagulation inhibitor
  • Thrombin
  • drospirenone
Topics
  • Adult
  • Androstenes (pharmacology)
  • Blood Coagulation (drug effects)
  • Contraceptives, Oral (pharmacology)
  • Female
  • Hemostasis (drug effects)
  • Humans
  • Lipoproteins (metabolism)
  • Menstrual Cycle
  • Protein S (metabolism)
  • Thrombin (metabolism)
  • Young Adult

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