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Risk of First Venous Thrombosis by Comparing Different Thrombin Generation Assay Conditions: Results from the MEGA
Kristien Winckers1, Eugenia Biguzzi2, Stella Thomassen1
1Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), University Maastricht, Maastricht, The Netherlands.
TH Open : Companion Journal to Thrombosis and Haemostasis
|March 21, 2025
Summary
Hypercoagulability increases venous thromboembolism (VTE) risk. Thrombin generation (TG) assays, especially those with a low procoagulant stimulus, effectively identify this heightened VTE risk.
Area of Science:
- Hematology
- Thrombosis Research
- Coagulation Assays
Background:
- Hypercoagulability is a significant risk factor for venous thromboembolism (VTE).
- Thrombin generation (TG) is a global assay measuring clotting tendency.
- The study investigates optimal TG assay conditions for detecting hypercoagulability.
Purpose of the Study:
- To compare different TG assay conditions for their ability to detect VTE risk.
- To assess the risk of first VTE associated with various TG parameters.
- To determine if slow-onset TG is optimal for identifying hypercoagulability.
Main Methods:
- Measured basal TG in plasma from 2,081 first VTE patients and 2,908 controls.
- Utilized low and high tissue factor (TF) concentrations, with and without activated protein C (APC).
- Calculated odds ratios (ORs) for VTE risk across TG parameter quartiles.
Main Results:
- Elevated thrombin peak height strongly correlated with VTE risk across all TF concentrations.
- Low TF stimulus showed the highest VTE risk association (OR 6.8).
- Increased normalized APC sensitivity ratio (nAPCsr), indicating APC resistance, was also linked to VTE risk (OR 3.4).
Conclusions:
- Increased thrombin generation is a significant risk factor for first VTE.
- Low procoagulant stimulus in TG assays is particularly effective for identifying VTE risk.
- TG assays provide valuable insights into hypercoagulability and VTE risk assessment.

