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CC BY 4.0 · TH Open 2025; 09: a25346123
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 (CARIM), University Maastricht, Maastricht, The Netherlands
,
Eugenia Biguzzi
2   Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands
,
Stella Thomassen
1   Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), University Maastricht, Maastricht, The Netherlands
,
Alexandra Heinzmann
1   Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), University Maastricht, Maastricht, The Netherlands
,
Frits R. Rosendaal 
2   Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands
,
Tilman M. Hackeng
1   Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), University Maastricht, Maastricht, The Netherlands
,
Astrid van Hylckama-Vlieg
2   Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands
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Abstract

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 the optimal responsive TG method for detecting hypercoagulability.

This study aimed to compare different TG assay conditions with respect to VTE risk and assess the risk of the first VTE.

Materials and 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 Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis (MEGA) study. TG parameters and normalised activated protein C sensitivity ratio (nAPCsr) were categorised into quartiles as measured in the controls. We calculated odds ratios (ORs) with 95% confidence intervals (CIs) of the first VTE for different TG categories.

Results

Under all assay conditions the thrombin peak height was associated with VTE risk: peak height of >75th percentile, at low TF OR 6.8 (95% CI 5.5–8.3), at high TF, OR 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 of <25th percentile obtained in controls. An increased nAPCsr (higher resistance to APC) was also associated with VTE risk, OR 3.4 (95% CI 2.8–4.1).

Conclusion

Increased TG is associated with the risk of first VTE, particularly when triggered with a low procoagulant stimulus.

Keywords

coagulation tests - odds ratio - risk factors - thrombin - venous thrombosis

Authors' Contributions

K.W.: data analysis and interpretation, writing the manuscript.


E.B.: data analysis, co-writing the final version of the manuscript.


S.T.: designing laboratory tests, planning the experiments, performing the experiments, collecting data, co-writing the final version of the manuscript.


A.H.: planning the experiments, performing the experiments, collecting data.


F.R.R.: co-writing the final version of the manuscript.


T.M.H.: developing the theory, supervising experiments, co-writing the final version of the manuscript.


A.v.H.V: data analysis and interpretation, co-writing the final version of the manuscript.




Publication History

Received: 06 December 2024

Accepted: 04 February 2025

Accepted Manuscript online:
07 February 2025

Article published online:
19 March 2025

© 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 M. 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 2025; 09: a25346123.
DOI: 10.1055/a-2534-6123
 

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