OC 51.5 - Effects of gender and hormonal status on thrombin generation in a large population-based cohort of twins and their family members

Tuesday, July 12, 2022

11:45 AM – 12:00 PM

Location: ExCel Center, S11A

Presentation Format: In-Person

Presenting Author(s)

Suzanne Zwaveling, PhD, MD

MD internal medicine
Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands
Breukelen, Utrecht, Netherlands

Co-Author(s)

SB

Saartje Bloemen

Postdoc
Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands
Maastricht, Limburg, Netherlands
EC

Elisabetta Castoldi, PhD

Associate Professor
Department of Biochemistry, CARIM, Maastricht University, Maastricht (The Netherlands)
Maastricht, Limburg, Netherlands
Ed

Eco de Geus

Professor
Department of Biological Psychology, Amsterdam Public Health Research Institute, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
Amsterdam, Noord-Holland, Netherlands
JH

Jouke-Jan Hottenga

Associate professor
Department of Biological Psychology, Amsterdam Public Health Research Institute, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
Amsterdam, Noord-Holland, Netherlands
TH

Tilman M. Hackeng, PhD

Chief Scientific Officer
Coagulation Profile, Maastricht, The Netherlands
Maastricht, Limburg, Netherlands
DB

Dorret Boomsma

Professor
Department of Biological Psychology, Amsterdam Public Health Research Institute, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
Amsterdam, Noord-Holland, Netherlands
CH

Coenraad Hemker

Professor
Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands
Amsterdam, Noord-Holland, Netherlands
GW

Gonneke Willemsen

Professor
Department of Biological Psychology, Amsterdam Public Health Research Institute, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
Amsterdam, Noord-Holland, Netherlands

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=306) 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.