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

Autor: Tchaikovski SN; University Clinic for Gynaecology and Obstetrics, RWTH Aachen, Germany; University Clinic for Gynaecology and Obstetrics, Otto von Guericke University Magdeburg, Germany. Electronic address: svetlana.tchaikovski@med.ovgu.de., Thomassen MCLGD; Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, the Netherlands., Stickeler E; University Clinic for Gynaecology and Obstetrics, RWTH Aachen, Germany., Bremme K; Department of Women's and Children's Health, Division of Obstetrics and Gynaecology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden., Rosing J; Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, the Netherlands.
Jazyk: angličtina
Zdroj: Thrombosis research [Thromb Res] 2021 Nov; Vol. 207, pp. 143-149. Date of Electronic Publication: 2021 Sep 29.
DOI: 10.1016/j.thromres.2021.09.018
Abstrakt: 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.
(Copyright © 2021. Published by Elsevier Ltd.)
Databáze: MEDLINE
Externí odkaz: