Resistance to activated protein C and impaired TFPI activity in women with previous hormone-induced venous thromboembolism

S.N. Tchaikovski*, M.C.L.G.D. Thomassen, E. Stickeler, K. Bremme, J. Rosing

*Corresponding author for this work

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Abstract

Introduction: Hormonal contraception is a well-known risk factor for venous thromboembolism (VTE). APC resistance and impaired functions of protein S and TFPI are thought to play an important role in the pathogenesis of hormone-related VTE. It is unknown, whether women, who develop VTE during hormonal contraception possess a vulnerability in these pathways, making them susceptible to thrombosis. Materials and methods: Plasma samples were obtained from 57 premenopausal women in average 15.3 years after hormone-associated VTE and from 31 healthy controls. Thrombin generation at high tissue factor (TF) in the absence and in the presence of activated protein C (APC) and at low TF without and with inhibiting anti-protein S- and anti-TFPI-antibodies was measured via calibrated automated thrombography. Results: Women with previous hormone-related thrombosis had higher thrombin generation at low TF, higher APC resistance, protein S- and TFPI ratios, differences: 219.9 nM IIa.min (95%CI:90.4 to 349.3); 1.88 (95% CI:0.71 to 3.05); 0.13 (95%CI:0.01 to 0.26) and 0.19 (95%CI:0.08 to 0.30), respectively. Thrombin generation at high TF without APC did not differ between the groups. Smoking decreased thrombin generation at low TF by -222.6 nM IIa.min (95%CI: -381.1 to -64.1), the APC sensitivity ratio by -2.20 (95%CI: -3.63 to -0.77) and the TFPI ratio by -0.16 (95%CI: -0.29 to -0.03), but did not influence thrombin generation at high TF. Discussion: We demonstrated impairment of the protein S/TFPI system and increased APC resistance in women with previous hormone-induced VTE. Smoking decreased thrombin generation at assay conditions, dependent on the function of the TFPI system.
Original languageEnglish
Pages (from-to)143-149
Number of pages7
JournalThrombosis Research
Volume207
DOIs
Publication statusPublished - 1 Nov 2021

Keywords

  • Contraceptives
  • Thrombosis
  • TFPI
  • Protein S
  • APC resistance
  • Smoking
  • FACTOR PATHWAY INHIBITOR
  • CARDIOVASCULAR RISK-FACTORS
  • D-DIMER LEVEL
  • THROMBIN GENERATION
  • ORAL-CONTRACEPTIVES
  • COAGULATION-FACTORS
  • PROTHROMBINASE
  • PLASMA
  • 1ST

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