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Effects of gender and hormonal status on thrombin generation in a large population-based cohort of twins and their family members

1Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands, Breukelen, Utrecht, Netherlands, 2Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands, Maastricht, Limburg, Netherlands, 3CARIM, Maastricht University, Maastricht, Not Applicable, Netherlands, 4Department of Biological Psychology, Amsterdam Public Health Research Institute, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands, Amsterdam, Noord-Holland, Netherlands, 5Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, Limburg, Netherlands, 6Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands, Amsterdam, Noord-Holland, Netherlands

Abstract Number: OC 51.5

Meeting: ISTH 2022 Congress

Theme: Women’s Health » Estrogens and Progestinics

Background: Risk factors for venous thrombosis (VT) include age, gender, genetics and life-style factors, e.g. oral contraceptive (OC) use. Thrombin generation (TG) correlates with a risk of VT.

Aims: We examined the association of TG with demographics, hormonal status and OC use in a large and well-characterised cohort of twins and family members. Using a cotwin-control design, the effect of OCs on TG within pairs discordant for OC use was determined.

Methods: TG data was available for 7,869 consenting participants (mean age: 45.1, range 18-98, 64.3% female) in the Netherlands Twin Register biobank. Data on demographics, hormonal status (incl. OC use) and medication use were obtained. TG was determined by calibrated automated thrombinography (CAT) in citrated plasma using 5 pM tissue factor (TF) and 4 µM phospholipids in the presence and absence of 20 nM thrombomodulin (TM). After excluding users of anticoagulants (n=101), TG was compared in men, women with a natural menstrual cycle, women using estrogen-containing OCs and post-menopausal women. TG differences were also examined in female monozygotic twins concordant (N&#3f306) and discordant (N = 152) for OC use.

Results: TG of women showed shorter lag-times, higher peak heights and higher endogenous thrombin potentials (ETPs) compared to men. Women using OCs had the most procoagulant TG profiles: higher ETP and peak, and shorter lag-time. All groups differed significantly, with post-menopausal women closer in value to men than women with a natural cycle. Similar patterns were seen in the presence of TM. The discordant cotwin-control analyses confirmed the OC effect: even after controlling for familial factors. OC use was associated with a less favorable profile (Table 1).

Conclusion(s): This study shows that factors known to increase VT risk (notably OC use) act by increasing TG. Our findings in discordant female monozygotic twin pairs provide strong evidence for a prothrombotic profile caused by OC use.

Table 1. TG parameters in MZF twin pairs concordant and discordant for OC use.

In case of discordant twins, the non-using twin is twin 1, the OC using twin is twin 2.
In bold p < .000, Italic p < .05

To cite this abstract in AMA style:

Zwaveling S, Bloemen S, Castoldi E, de Geus E, Hottenga J, Hackeng T, Boomsma D, Hemker C, Willemsen G. Effects of gender and hormonal status on thrombin generation in a large population-based cohort of twins and their family members [abstract]. https://abstracts.isth.org/abstract/effects-of-gender-and-hormonal-status-on-thrombin-generation-in-a-large-population-based-cohort-of-twins-and-their-family-members/. Accessed October 2, 2023.

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