Download PDF
CC BY 4.0 · TH Open
DOI: 10.1055/a-2534-6123
Original Article

Risk of first venous thrombosis by comparing different thrombin generation assay conditions: results from the MEGA case-control study.

Kristien Winckers
1   Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, maastricht, Netherlands
,
Eugenia Biguzzi
2   IRCCS Maggiore Hospital, University of Milan, Milan, Italy
,
Stella Thomassen
3   Biochemistry, University of Maastricht, Maastricht, Netherlands
,
Alexandra Heinzmann
4   Department of Biochemisty, Maastricht University, Cardiovascular Research Institute Maastricht (CARIM), Maastricht, Netherlands
,
Frits R. Rosendaal 
5   Clinical Epidemiology, Leiden University Medical Center, Leiden, Netherlands
,
Tilman Mathias Hackeng
6   Biochemistry, University Maastricht, Maastricht, Netherlands
,
Astrid van Hylckama Vlieg
5   Clinical Epidemiology, Leiden University Medical Center, Leiden, Netherlands
› Author Affiliations
› Further Information
Also available at
  PDF Download

Background: Hypercoagulability is a risk factor for venous thromboembolism (VTE). Thrombin generation (TG) is a global coagulation assay that measures an individual’s clotting tendency. We hypothesise that slow onset TG (achieved by using a low procoagulant stimulus or an inhibitor of coagulation) is optimal responsive to detect hypercoagulability. Objectives: To compare different TG assay conditions with respect to VTE risk and to assess the risk of first VTE. Methods: Basal TG at low tissue factor (TF) concentration and high TF concentration in the presence and absence of activated protein C (APC) were measured in plasma samples from 2,081 patients with first VTE and 2,908 healthy controls from the MEGA study. TG parameters and nAPCsr were categorised into quartiles as measured in the controls. We calculated odds ratios (ORs) with 95% confidence intervals of a first VTE for different TG categories. Results: Under all assay conditions the thrombin peak height was associated with VTE risk: peak height > 75th percentile, at low TF odds ratio (OR) 6.8 (95% confidence interval (CI) 5.5 – 8.3), at high TF, odds ratio 3.0 (95% CI 2.5 – 3.6) and at high TF + APC, OR 3.8 (95% CI 3.2 - 4.5), all compared with a peak height < 25th percentile obtained in controls. An increased nAPCsr (higher resistance to APC) was also associated with VTE risk, odds ratio 3.4 (95% CI 2.8 – 4.1). Conclusions: increased TG is associated with the risk of first VTE, particularly when triggered with a low procoagulant stimulus.



Publication History

Received: 06 December 2024

Accepted after revision: 04 February 2025

Accepted Manuscript online:
07 February 2025

© . The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).

Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

Bibliographical Record
Kristien Winckers, Eugenia Biguzzi, Stella Thomassen, Alexandra Heinzmann, Frits R. Rosendaal, Tilman Mathias Hackeng, Astrid van Hylckama Vlieg. Risk of first venous thrombosis by comparing different thrombin generation assay conditions: results from the MEGA case-control study.. TH Open ; 0: a25346123.
DOI: 10.1055/a-2534-6123