Resistance to activated protein C and impaired TFPI activity in women with previous hormone-induced venous thromboembolism
Autor: | Katarina Bremme, Jan Rosing, S. N. Tchaikovski, E. Stickeler, M. C. L. G. D. Thomassen |
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Přispěvatelé: | Biochemie, RS: Carim - B03 Cell biochemistry of thrombosis and haemostasis, RS: Carim - B01 Blood proteins & engineering |
Rok vydání: | 2021 |
Předmět: |
D-DIMER LEVEL
medicine.medical_specialty TFPI FACTOR PATHWAY INHIBITOR 1ST Protein S Pathogenesis Tissue factor Prothrombinase Internal medicine CARDIOVASCULAR RISK-FACTORS medicine THROMBIN GENERATION Risk factor COAGULATION-FACTORS PLASMA biology business.industry Smoking ORAL-CONTRACEPTIVES Contraceptives Thrombosis PROTHROMBINASE Hematology medicine.disease APC resistance Endocrinology biology.protein business Protein C medicine.drug Hormone |
Zdroj: | Thrombosis Research, 207, 143-149. Elsevier Science |
ISSN: | 0049-3848 |
Popis: | 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. |
Databáze: | OpenAIRE |
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