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Changes in haemostatic parameters during the menstrual cycle and subsequent use of drospirenone-containing oral
S N Tchaikovski1, M C L G D Thomassen2, S D Costa3
1Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands; University Women´s Hospital, Otto-von-Guericke University, Magdeburg, Germany.
Introduction:
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.
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