The Contribution of Corn Trypsin Inhibitor on Thrombin Generation Kinetics in Trauma Patients: A Comparative Analysis
Authors: Navarro Sergio M , Thompson Riley J. , Spears Grant M , Bailey Kent R , Dong Jing-Fei , Kozar Rosemary A , Chen Dong , Pruthi Rajiv K , Park Myung S 
Published: December 2024

Trauma-induced coagulopathy (TIC) is common after injury and reliable quantification of its severity is lacking. The objective of this study was to evaluate whether thrombin generation would be significantly altered if whole blood samples from trauma patients were collected without (citrate-only) and with corn trypsin inhibitor (CTI+).

In a prospective cohort study, 36 trauma pts presenting to a Level I Trauma Center within 12 hours of injury, had whole blood collected simultaneously in citrate-only (3.2%) and citrated plus CTI (CTI+ [final 25 ug/mL]), and processed to platelet free plasma by double centrifugation (3000g, 15 minutes). Samples were stored at -80C with no thawing until analysis. Thrombin generation profiles were measured using the ST Genesia assay (Diagnostica STAGO SAS) and parameters included endogenous thrombin potential (ETP), lag time (LT), peak height, start of tail, velocity index, and time to peak (ttPeak) were analyzed for trauma pts. Data presented as median [IQR] or n (%), with paired t-test and Spearman's correlation analysis were performed between citrated non-CTI and citrated CTI spiked blood samples, with p-value &lt;0.05 statistically significant.

Pts presented with significant injury ISS 13 [5, 21], age 45 [29, 59] years, 80.6% male, BMI 26.9 [25.4, 28.3], 94.4% blunt trauma, 22.3% had surgery by day 1 of admission. Significant differences were found between the citrated-only and CTI +tubes in several thrombin generation parameters: ETP (1339 Nm*min [1172.5,1417], 1124.5 [925.4,1285], p&lt;0.001), peak height (222.3 Nm [186.0, 275.6], 160.6 [132.7,208.3], p&lt;0.001), ttPeak (5.64 min [4.86,6.63], 6.19 [5.36, 7.34], p&lt;0.001), start of tail (19.4 min [17.6,21.3], 21.6 [18.9, 23.6], p=0.014), and velocity index (117.6 Nm/min [77.9, 163.1], 71.9 [54.9,106.0], p&lt;0.001). However, LT (3.14 min [2.74, 3.90], 3.08 [2.84, 3.96], p=0.665) did not show a statistically significant difference. Spearman's correlation analysis showed high correlation between citrate-only and CTI+ citrated plasma samples, with Spearman's rank correlation coefficients for LT (0.941), peak height (0.760), ttPeak (0.928), ETP (0.770), start of tail (0.869), and velocity index (0.766) respectively.

The results suggest that use of CTI+ decrease thrombin generation kinetics from blood samples obtained from trauma patients. These findings underscore the need for careful consideration of sample collection and processing for use of thrombin generation assays in clinical setting. However, there is very strong correlation of the thrombin parameters obtained from citrated-only plasma to CTI+ plasma samples, suggesting they capture similar information.

CTI-spiked citrated tubes appear to reduce contact activation with respect to thrombin generation profiles compared to standard citrated only tubes. This should be a consideration for platform-based lab processing of thrombin generation assays for assessment of coagulopathy after injury; however, given the cost of CTI, citrated-only tubes can be an option for characterization of thrombin generation profile in clinical samples.