Risk of first venous thrombosis by comparing different thrombin generation assay conditions: results from the MEGA case-control study.
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) i...
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| author | Kristien Winckers Eugenia Biguzzi Stella Thomassen Alexandra Heinzmann Frits R. Rosendaal Tilman Mathias Hackeng Astrid van Hylckama Vlieg |
| author_facet | Kristien Winckers Eugenia Biguzzi Stella Thomassen Alexandra Heinzmann Frits R. Rosendaal Tilman Mathias Hackeng Astrid van Hylckama Vlieg |
| author_sort | Kristien Winckers |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-b121f92076f2454eacd6ec9b929de97b |
| institution | Kabale University |
| issn | 2512-9465 |
| language | English |
| publisher | Georg Thieme Verlag KG |
| record_format | Article |
| series | TH Open |
| spelling | doaj-art-b121f92076f2454eacd6ec9b929de97b2025-02-08T01:48:47ZengGeorg Thieme Verlag KGTH Open2512-946510.1055/a-2534-6123Risk of first venous thrombosis by comparing different thrombin generation assay conditions: results from the MEGA case-control study.Kristien Winckers0Eugenia Biguzzi1Stella Thomassen2Alexandra Heinzmann3Frits R. Rosendaal4https://orcid.org/0000-0003-2558-7496Tilman Mathias Hackeng5Astrid van Hylckama Vlieg6Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht UniversityIRCCS Maggiore Hospital, University of Milan, Milan, ItalyBiochemistry, University of Maastricht, Maastricht, NetherlandsDepartment of Biochemisty, Maastricht University, Cardiovascular Research Institute Maastricht (CARIM), Maastricht, NetherlandsClinical Epidemiology, Leiden University Medical Center, Leiden, NetherlandsBiochemistry, University Maastricht, Maastricht, NetherlandsClinical Epidemiology, Leiden University Medical Center, Leiden, NetherlandsBackground: 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.http://www.thieme-connect.de/DOI/DOI?10.1055/a-2534-6123 |
| spellingShingle | 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 |
| title | Risk of first venous thrombosis by comparing different thrombin generation assay conditions: results from the MEGA case-control study. |
| title_full | Risk of first venous thrombosis by comparing different thrombin generation assay conditions: results from the MEGA case-control study. |
| title_fullStr | Risk of first venous thrombosis by comparing different thrombin generation assay conditions: results from the MEGA case-control study. |
| title_full_unstemmed | Risk of first venous thrombosis by comparing different thrombin generation assay conditions: results from the MEGA case-control study. |
| title_short | Risk of first venous thrombosis by comparing different thrombin generation assay conditions: results from the MEGA case-control study. |
| title_sort | risk of first venous thrombosis by comparing different thrombin generation assay conditions results from the mega case control study |
| url | http://www.thieme-connect.de/DOI/DOI?10.1055/a-2534-6123 |
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