Thrombin generation profiles as predictors of symptomatic venous thromboembolism after trauma

Abstract

Background Reliable biomarkers predictive of venous thromboembolism (VTE) after acute trauma are uncertain. The objective of the study was to identify risk factors for symptomatic VTE after trauma, including individual plasma coagulome characteristics as reflected by thrombin generation. Methods In a prospective, case-cohort study, trauma patients were enrolled over the 4.5 year period, 2011–2015. Blood was collected by venipuncture into 3.2% trisodium citrate at 0, 6, 12, 24 and 72 hours after injury, and at hospital discharge. Platelet poor plasma was stored at −80°C until analysis. Thrombin generation, as determined by the calibrated automated thrombogram (CAT) using 5 pM tissue factor (TF)/4 uM phospholipid (PS), was reported as peak height (nM thrombin) and time to peak height (ttPeak [minutes]). Data are presented as median [IQR] or hazard ratio (HR) with (95% CI). Results Among 453 trauma patients (ISS=13.0 [6.0, 22.0], hospital LOS=4.0 [2.0, 10.0] days, age=49 [28, 64] years, 71% male, 96% with blunt mechanism, mortality 3.2%), 83 developed symptomatic VTE within 92 days after injury (35 [42%] after hospital discharge). In a weighted, multivariate Cox model that included clinical and CAT characteristics available within 24 hours of admission, increased patient age (1.35 [1.19,1.52] per 10 years, P<0.0001), body mass index (BMI) ≥ 30 kg/m2 (4.45 [2.13,9.31], p <0.0001), any surgery requiring general anesthesia (2.53 [1.53,4.19], P=0.0003) and first available ttPeak (1.67[1.29, 2.15], p <0.00001) were independent predictors of incident symptomatic VTE within 92 days after trauma (C-statistic=0.799). Conclusion The individual’s plasma coagulome (as reflected by thrombin generation) is an independent predictor of VTE after trauma. Clinical characteristics and ttPeak can be used to stratify acute trauma pts into high and low risk for VTE.

New considerations on pathways involved in acute traumatic coagulopathy: the thrombin generation paradox

“…The main advantage of this procoagulant mechanism in terms of survival could be to counterbalance the effect of coagulation factors depletion and aPC-mediated fibrinolysis. However, thrombosis is the price to pay to lower mortality [24]: a recent publication concluded that a procoagulant phenotype was a predictor of symptomatic venous thromboembolism after trauma [48]. These observations are consistent with the fact that, after several days, patients with ATC present higher mortality rates despite the restoration of normal blood pressure.…”

Sufficient Thrombin Generation Despite 95% Hemodilution: An In Vitro Experimental Study

“…Furthermore, trauma patients exhibit increased thrombin generation in comparison with healthy controls [26,[30][31][32]. Importantly, patients hospitalized after trauma encounter a substantially elevated risk of venous thromboembolism, and elevated thrombin generation has been shown to be an independent predictor for venous thromboembolic events in this patient cohort [33,34].…”

Clinical Cellular Therapeutics Accelerate Clot Formation

“…Park et al identified CAT lag time and time to thrombin peak as risk factors for development of venous thromboembolism in patients after acute trauma, HR 1.66 (1.06, 2.60) p < .028 and HR 2.02 (1.45, 2.80) p < .001, respectively. They conclude that CAT is potentially a useful clinical tool in predicting the occurrence of VTE after injury . CAT is advantageous because it is not confounded by cellular components of blood and is specific for thrombin production.…”