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Published on: February 27, 2026
The influence of tissue factor and tissue factor pathway inhibitor polymorphisms on thrombin generation in stable
Trine B Opstad1, Alf-Aage R Pettersen, Vibeke Bratseth
1Department of Cardiology, Center for Clinical Heart Research, Oslo University Hospital, Oslo, Norway. trineoa@medisin.uio.no
Insights
Specific gene variations in tissue factor (TF) and TF pathway inhibitor (TFPI) influence thrombin generation in coronary heart disease patients. These genetic factors correlate with blood clotting markers, impacting cardiovascular risk.
Area of Science:
- Cardiovascular Genetics
- Hemostasis and Thrombosis
Background:
- Coronary heart disease (CHD) involves complex hemostatic mechanisms.
- Thrombin generation is a critical factor in thrombotic events.
Purpose of the Study:
- To investigate the impact of tissue factor (TF) and TF pathway inhibitor (TFPI) gene polymorphisms on thrombin generation in stable CHD patients.
- To correlate circulating TF and TFPI levels with thrombin generation parameters.
Main Methods:
- Studied 1,001 patients with stable coronary heart disease.
- Assessed in vivo thrombin generation using prothrombin fragment 1 and 2 levels.
- Measured ex vivo thrombin generation potential with the calibrated automated thrombogram assay.
- Analyzed TF and TFPI polymorphisms and circulating levels.
Main Results:
- TF 5466 and TFPI -399 polymorphisms were linked to increased in vivo thrombin generation.
- Specific TF genotypes (-1812 TT, -603 GG) correlated with reduced peak thrombin and activation rates.
- TFPI -33 TC genotype was associated with prolonged lag time and time to peak thrombin generation.
- Significant correlations were found between TFPI levels and both in vivo and ex vivo thrombin generation markers.
Conclusions:
- Certain TF and TFPI polymorphisms significantly modulate thrombin generation in CHD.
- Circulating TFPI levels are strongly associated with thrombin generation dynamics.
- These findings highlight the role of genetic factors in thrombotic risk in coronary heart disease.
Abstract:
In patients with stable coronary heart disease (n = 1,001) we investigated the influence of tissue factor (TF) and TF pathway inhibitor (TFPI) polymorphisms on thrombin generation in vivo, measured by prothrombin fragment (F) 1 and 2, and the potential to generate thrombin ex vivo, measured by the calibrated automated thrombogram assay. Additionally, circulating levels of TF and TFPI were correlated to the different parameters of thrombin generation. The TF 5466 and TFPI -399 polymorphisms associated with higher thrombin generation in vivo, the latter also with a prolonged lag time of the thrombin generation ex vivo(p < 0.05 for all).The TF -1812 TT and the TF -603 GG genotypes were associated with lower peak thrombin and a decreased average net rate of thrombin activation during the propagation phases (p ≤ 0.05), and the TFPI -33 TC genotype with prolonged lag time (p < 0.05) and additionally time to peak (p = 0.06). Strong correlations between TFPI levels, prothrombin fragment 1 and 2 as well as calibrated automated thrombogram parameters were observed.
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