Skip to main content
ISTH 2023 Main banner
Back

    Oral Communication

    Women’s Health

    Hemostatic Balance and Anticoagulants in Women’s Health

    OC 35.1 - Response of thrombin generation to rivaroxaban in twin-families: influence of sex and contraceptives

    Monday, June 26, 2023
    10:45 – 11:00 ET
    Room: 511
    Session Available As: On-Demand

      Presenting Author(s)

    • Suzanne Zwaveling, PhD, MD (she/her/hers)

      resident internal medicine
      Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands
      Breukelen, Utrecht, Netherlands

      • Co-Author(s)

    • SB

      Saartje Bloemen

      Postdoc
      Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands
      Maastricht, Limburg, Netherlands

    • Elisabetta Castoldi, PhD

      Associate Professor
      Department of Biochemistry, CARIM, Maastricht University, Maastricht (The Netherlands)
      Maastricht, Limburg, Netherlands

    • EG

      Eco Geus, de

      Professor, Faculty of Behavioural and Movement Sciences, Biological Psychology.
      Department of Biological Psychology, Amsterdam Public Health Research Institute, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
      Amsterdam, Noord-Holland, Netherlands

    • JH

      Jouke Jan Hottenga

      Senior Researcher
      Department of Biological Psychology, Amsterdam Public Health Research Institute, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
      Amsterdam, Noord-Holland, Netherlands

    • TH

      Tilman M. Hackeng, PhD

      Chief Scientific Officer
      Coagulation Profile, Maastricht, The Netherlands
      Maastricht, Limburg, Netherlands

    • DB

      Dorret Boomsma

      Professor, Faculty of Behavioural and Movement Sciences, Biological Psychology
      Department of Biological Psychology, Amsterdam Public Health Research Institute, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
      Amsterdam, Noord-Holland, Netherlands

    • GW

      Gonneke Willemsen

      Professor, Faculty of Behavioural and Movement Sciences, Biological Psychology
      Department of Biological Psychology, Amsterdam Public Health Research Institute, Vrije Universiteit
      Amsterdam, Noord-Holland, Netherlands

    • CH

      Coenraad Hemker

      Professor Emeritus
      Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands
      Maastricht, Limburg, Netherlands

    Background: Sex and estrogen-containing contraceptives (ECs) are established risk factors for venous thromboembolism (VTE), but little is known about their effects on anticoagulant treatment.

    Aims: To gain insight into the effects of sex and EC use on the thrombin generation (TG) response to anticoagulant treatment, we compared thrombin generation in the presence and absence of rivaroxaban for men, post-menopausal women, women with a natural cycle and women taking ECs. In follow-up analyses, we compared TG responses in monozygotic female (MZF) twins, concordant and discordant for EC.

    Methods: TG in the presence and absence of 300 nM rivaroxaban was measured using calibrated automated thrombinography in plasma from 7,439 participants, including 566 MZF twin pairs, of the Netherlands Twin Register. Mixed model linear regression analyses tested associations of sex and EC for endogenous thrombin potential (ETP), peak levels and their inhibition by rivaroxaban (% inhibition). Within the MZF pair analyses were carried out by paired t-tests.

    Results: On average, rivaroxaban inhibited ETP by 45% and peak by 89%, with an individual variation (SD) of 10.6% and 6.6% respectively. The lowest peak and ETP levels with and without rivaroxaban as well as the highest % inhibition were observed in men. This was followed by post-menopausal women and next by women with a natural cycle. Women taking ECs showed by far the highest peak and ETP levels and a lower response to rivaroxaban. The strong effect of ECs was also seen in twins discordant for EC use, with an unfavorable profile in the EC-using twin. Concordant twins did not differ from each other.

    Conclusion(s): There is a marked effect of EC use on the response of thrombin generation to rivaroxaban. The results for discordant twin pairs, who are matched for sex, age and genotype, point to a causal effect.

    Learning Objectives:

    • Recognize that the use of estrogen-containing contraceptives has a marked effect on the response of thrombin generation to rivaroxaban
    • Acknowledge that the inhibition of thrombin generation by a fixed dose of rivarobaxan is highly variable
    • Understand that the inhibition of thrombin generation by rivaroxaban is partly hereditary