Thrombin Generation in Critically Ill Adults: A Systematic Review of Venous Thromboembolism and Pharmacological Thromboprophylaxis.
Abstract
Background
Venous thromboembolism (VTE) remains an important complication in critically ill adults despite standard pharmacological thromboprophylaxis. Thrombin generation assays (TGAs) offer a global functional assessment of coagulation by capturing the kinetics and magnitude of thrombin formation and may complement conventional measures of coagulation such as anti-Xa activity.
Methods
The review was conducted according to JBI methodology and reported per PRISMA guidelines. We searched MEDLINE, Embase, and CENTRAL from inception to December 18, 2025. We included studies of adults (≥18 years) managed in high-acuity or intensive care settings with TGA measurements reported in relation to VTE incidence or thromboprophylaxis effect.
Results
We included 15 eligible prospective studies comprising 2,250 patients (9 surgical trauma cohorts, 4 medical ICU cohorts, 2 mixed ICU cohorts). Calibrated automated thrombography (CAT) was the most used TGA platform (80.0%). Eleven studies (73.3%) evaluated associations between TGA and VTE incidence, with inconsistent findings. Some trauma cohorts identified shorter time-to-peak thrombin or lag time as predictors of VTE, while other studies found no significant associations. Of eight studies (53.3%) assessing TGA pharmacodynamics, seven measured anti-Xa activity, which correlated with lower endogenous thrombin potential and peak thrombin.
Conclusion
TGA most consistently served as a pharmacodynamic measure of low-molecular-weight heparin effect: anti-Xa activity correlated with suppressed endogenous thrombin potential and peak thrombin. TGA did not reliably predict VTE, though shorter time-to-peak and lag time preceded thrombosis in trauma cohorts. TGA should be advanced as a coagulation-phenotyping tool in prospective ICU studies with standardized assays, consistent sampling in relation to dose timing, and concurrent anti-Xa and thrombin generation measurement.