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Published on: September 9, 2012
Relationships between coagulation factors and thrombin generation in a general population with arterial and venous
Pauline C S van Paridon1,2, Marina Panova-Noeva2,3, Rene van Oerle1
1Laboratory for Clinical Thrombosis and Hemostasis, Department of Internal Medicine, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Center, Maastricht, 6200 MD, the Netherlands.
Insights
Individuals with a history of thrombosis show significantly stronger associations between coagulation factors and thrombin generation compared to healthy individuals. These findings suggest lasting changes in the blood
Area of Science:
- Cardiovascular Medicine
- Hematology
- Thrombosis Research
Background:
- Investigating the interplay between coagulation factors and thrombin generation.
- Comparing individuals with thrombosis history to cardiovascular healthy controls.
- Utilizing a large population-based cohort for robust analysis.
Purpose of the Study:
- To identify relationships between coagulation factors and plasma thrombin generation.
- To compare these relationships in individuals with arterial/venous thrombosis versus healthy individuals.
- To understand the impact of thrombotic history on hemostasis.
Main Methods:
- Analysis of 502 arterial disease patients, 195 venous thrombosis patients, and 1402 healthy controls from the Gutenberg Health Study (GHS).
- Assessment of Calibrated Automated Thrombography (CAT) and measurement of coagulation factors using BCS XP Systems.
- Application of multiple linear regression analysis, adjusted for age, sex, and antithrombotic therapy.
Main Results:
- Lag time to thrombin formation showed reversed associations with coagulant/anticoagulant factors in thrombosis groups (10x effect size).
- Endogenous thrombin potential was positively influenced by factors II, VIII, X, and IX across all groups.
- Effect sizes for these associations were significantly higher (4x) in arterial and venous disease groups compared to controls.
Conclusions:
- Individuals with a history of thrombosis exhibit a heightened sensitivity of thrombin generation to coagulation factors.
- Sustained alterations in the plasma coagulome are implicated in subjects with thrombotic vascular disease.
- These alterations persist despite ongoing antithrombotic therapy, highlighting potential therapeutic targets.
Background:
The current study aims to identify the relationships between coagulation factors and plasma thrombin generation in a large population-based study by comparing individuals with a history of arterial or venous thrombosis to cardiovascular healthy individuals.
Methods:
This study comprised 502 individuals with a history of arterial disease, 195 with history of venous thrombosis and 1402 cardiovascular healthy individuals (reference group) from the population-based Gutenberg Health Study (GHS). Calibrated Automated Thrombography was assessed and coagulation factors were measured by means of BCS XP Systems. To assess the biochemical determinants of TG variables, a multiple linear regression analysis, adjusted for age, sex and antithrombotic therapy, was conducted.
Results:
The lag time, the time to form the first thrombin, was mainly positively associated with the natural coagulant and anti-coagulant factors in the reference group, i.e. higher factors result in a longer lag time. The same determinants were negative for individuals with a history of arterial or venous thrombosis, with a 10 times higher effect size. Endogenous thrombin potential, or area under the curve, was predominantly positively determined by factor II, VIII, X and IX in all groups. However, the effect sizes of the reported associations were 4 times higher for the arterial and venous disease groups in comparison to the reference group.
Conclusion:
This large-scale analysis demonstrated a stronger effect of the coagulant and natural anti-coagulant factors on the thrombin potential in individuals with a history of arterial or venous thrombosis as compared to healthy individuals, which implicates sustained alterations in the plasma coagulome in subjects with a history of thrombotic vascular disease, despite intake of antithrombotic therapy.
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