Combined oral contraceptives may activate the contact system in healthy women

Jesper Strandberg; Inger Lise Gade; Yaseelan Palarasah; Jørgen Brodersen Gram; Søren Risom Kristensen; Johannes Jakobsen Sidelmann

doi:10.1016/j.rpth.2023.100118

Combined oral contraceptives may activate the contact system in healthy women

Res Pract Thromb Haemost. 2023 Mar 13;7(2):100118. doi: 10.1016/j.rpth.2023.100118. eCollection 2023 Feb.

Authors

Jesper Strandberg¹, Inger Lise Gade², Yaseelan Palarasah³, Jørgen Brodersen Gram^{3

4}, Søren Risom Kristensen^{1

5}, Johannes Jakobsen Sidelmann^{3

5}

Affiliations

¹ Department of Clinical Biochemistry, The Coagulation Unit, Aalborg University Hospital, Aalborg, Denmark.
² Department of Haematology and Clinical Cancer Research Centre, Aalborg University Hospital, Aalborg, Denmark.
³ Department of Clinical Biochemistry, Unit for Thrombosis Research, University Hospital of Southern Denmark, Esbjerg, Denmark.
⁴ Department of Regional Health Research, Unit for Thrombosis Research, University Hospital of Southern Denmark, Esbjerg, Denmark.
⁵ Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.

Abstract

Background: The contact system (CAS) is part of the coagulation system, consisting of a group of plasma proteins stimulating inflammation, coagulation, and fibrinolysis when activated. CAS can be triggered by several activating surfaces, and CAS may play a potential role in thrombus formation. Combined oral contraceptives (COCs) are known to increase the risk of venous thromboembolism, and COCs induce various prothrombotic changes in the coagulation system, whereas the effect of COC on CAS has not been thoroughly investigated.

Objectives: To investigate CAS in COC users compared with nonusers.

Methods: Blood samples from 62 study subjects, 30 COC users, and 32 nonusers, were analyzed. Coagulation factor XII (FXII), prekallikrein (PK), H-Kininogen (HK), cleaved HK (cHK), C1-esterase inhibitor (C1-inh), and the endogenous kallikrein potential (EKP) were measured.

Results: COC users had significantly higher FXII (median, 38.4 vs 28.9 mg/L) and lower C1-inh levels (0.20 vs 0.23 g/L) than nonusers. The levels of PK and HK were not significantly different. Measurement of EKP indicated an increased capacity of CAS in COC users (1860 vs 1500 nmol/L × min), and increased plasma levels of cHK (2.02 vs 1.07 μg/L) indicated an increased activity in vivo.

Conclusion: This study demonstrates an increased CAS capacity in women using COC compared with nonusers and also an increased activity in vivo. The results indicate that increased contact activation may contribute to the increased thrombotic risk caused by COC.

Keywords: combined oral contraceptives; complement C1 inhibitor protein; contact system; endogenous kallikrein potential; factor XII.