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

Marjolein Raps; Frans M. Helmerhorst; Kathrin Fleischer; Anders E. A. Dahm; Frits R. Rosendaal; Jan Rosing; Pieter Reitsma; Per Morten Sandset; Huib A. A. M. van Vliet

doi:10.1160/TH12-10-0771

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

Marjolein Raps^*, Frans M. Helmerhorst, Kathrin Fleischer, Anders E. A. Dahm, Frits R. Rosendaal, Jan Rosing, Pieter Reitsma, Per Morten Sandset, Huib A. A. M. van Vliet

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

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.

Original language	English
Pages (from-to)	606-613
Journal	Thrombosis and Haemostasis
Volume	109
Issue number	4
DOIs	https://doi.org/10.1160/TH12-10-0771
Publication status	Published - Apr 2013

Keywords

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

Access to Document

10.1160/TH12-10-0771

Cite this

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title = "The effect of different hormonal contraceptives on plasma levels of free protein S and free TFPI",

abstract = "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.",

keywords = "APC resistance, deep-vein thrombosis, oral contraceptives, protein C/S pathway, tissue factor pathway inhibitor (TFPI)",

author = "Marjolein Raps and Helmerhorst, {Frans M.} and Kathrin Fleischer and Dahm, {Anders E. A.} and Rosendaal, {Frits R.} and Jan Rosing and Pieter Reitsma and Sandset, {Per Morten} and {van Vliet}, {Huib A. A. M.}",

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AU - Raps, Marjolein

AU - Helmerhorst, Frans M.

AU - Fleischer, Kathrin

AU - Dahm, Anders E. A.

AU - Rosendaal, Frits R.

AU - Rosing, Jan

AU - Reitsma, Pieter

AU - Sandset, Per Morten

AU - van Vliet, Huib A. A. M.

PY - 2013/4

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N2 - 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.

AB - 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.

KW - APC resistance

KW - deep-vein thrombosis

KW - oral contraceptives

KW - protein C/S pathway

KW - tissue factor pathway inhibitor (TFPI)

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