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The effect of different hormonal contraceptives on plasma levels of free protein S and free TFPI

Journal: Thrombosis and Haemostasis
ISSN: 0340-6245
DOI: http://dx.doi.org/10.1160/TH12-10-0771
Issue: 2013: 109/4 (Apr) pp. 569-768
Pages: 606-613

The effect of different hormonal contraceptives on plasma levels of free protein S and free TFPI

M. Raps (1), F. M. Helmerhorst (2), K. Fleischer (3), A. E. A. Dahm (4), F. R. Rosendaal (1), J. Rosing (5), P. Reitsma (6), P. M. Sandset (4), H. A. A. M. van Vliet (2, 7)

(1) Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands; (2) Department of Reproductive Medicine, Leiden University Medical Center, Leiden, the Netherlands; (3) Department of Obstetrics and Gynaecology, University Medical Center St. Radboud, Nijmegen, the Netherlands; (4) Department of Haematology, Oslo University Hospital, and University of Oslo, Oslo, Norway; (5) Department of Biochemistry, Maastricht University, Maastricht, the Netherlands; (6) Department of Haemostasis and Thrombosis, Leiden University Medical Center, Leiden, the Netherlands; (7) Department of Gynaecology Catharina Hospital, Eindhoven, the Netherlands

Keywords

APC resistance, Deep-vein thrombosis, protein C/S pathway, oral contraceptives, tissue factor pathway inhibitor (TFPI)

Summary

Use of combined oral contraceptives is associated with a three- to six-fold increased risk of venous thrombosis. Hormonal contraceptives induce acquired resistance to activated protein C (APC), which predicts the risk of venous thrombosis. The biological basis of the acquired APC resistance is unknown. Free protein S (PS) and free tissue factor pathway inhibitor (TFPI) are the two main determinants of APC. Our objective was to assess the effect of both hormonal and non-hormonal contraceptives with different routes of administration on free TFPI and free PS levels. We conducted an observational study in 243 users of different contraceptives and measured APC sensitivity ratios (nAPCsr), free TFPI and free PS levels. Users of contraceptives with the highest risk of venous thrombosis as reported in recent literature, had the lowest free TFPI and free PS levels, and vice versa, women who used contraceptives with the lowest risk of venous thrombosis had the highest free TFPI and free PS levels. An association was observed between levels of free TFPI and nAPCsr, and between free PS and nAPCsr. The effect of oral contraceptives on TFPI and PS is a possible explanation for the increased risk of venous thrombosis associated with oral contraceptives.

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