Endogenous thrombin potential changes during the first cycle of oral contraceptive use Journal Article


Authors: Westhoff, C. L.; Pike, M. C.; Cremers, S.; Eisenberger, A.; Thomassen, S.; Rosing, J.
Article Title: Endogenous thrombin potential changes during the first cycle of oral contraceptive use
Abstract: Objectives Venous thromboembolism (VTE) risk increases within months of combination oral contraceptive (COC) initiation. Because elevated endogenous thrombin potential (ETP) has been found in several studies to be a VTE risk factor, we evaluated the extent of ETP changes during the initial cycle of an ethinyl estradiol (EE) and levonorgestrel (LNG) COC. We also assessed the relationship between ETP changes and systemic EE and LNG concentrations. Study design Participants provided multiple blood samples during a first 21-day cycle of a 30-mcg EE/150-mcg LNG COC and after a further 7 days without an active COC. Thrombin generation measured with and without addition of activated protein C (APC) yielded ETP+APC and ETP-APC and the normalized APC sensitivity ratio (nAPCsr). EE and LNG pharmacokinetic analyses were conducted over 24 h after the first COC tablet and again at steady state. Results Thrombin generation was determined in 16 of the 17 women who completed the study. Mean ETP-APC increased steadily to 21% above baseline at 24 h after the 6th COC tablet (COC624; p<.001) and to 28% above baseline at steady state (COC21; p<.001). The percentage increase in mean ETP+APC was considerably more — 54% at COC624 and 79% at steady state. Mean nAPCsr increased by 28% at COC624 and by 41% at steady state. Higher concentrations of EE or LNG were not correlated with greater increases in ETP. Conclusions ETP increases during the first COC cycle were substantial. Implications The early increases in ETP may provide biological support for the rapid increase in VTE risk during initial COC use. The lack of association between this clotting system perturbation and the systemic EE concentration is surprising and deserves further study. © 2017 Elsevier Inc.
Keywords: venous thromboembolism; oral contraceptives; protein c; endogenous thrombin potential
Journal Title: Contraception
Volume: 95
Issue: 5
ISSN: 0010-7824
Publisher: Elsevier Inc.  
Date Published: 2017-05-01
Start Page: 456
End Page: 463
Language: English
DOI: 10.1016/j.contraception.2017.01.001
PROVIDER: scopus
PMCID: PMC5466838
PUBMED: 28088496
DOI/URL:
Notes: Article -- Export Date: 3 July 2017 -- Source: Scopus
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  1. Malcolm Pike
    141 Pike