Early thrombin formation capacity in trauma patients and association with venous thromboembolism.
Incidence of venous thromboembolism (VTE) in adult trauma patients is high despite mechanical and pharmacologic prophylaxis. We hypothesized that thrombin formation capacity as measured by calibrated automated thrombogram (CAT) is increased early in hospitalization and is associated with the development of VTE.


METHODS
We conducted a prospective study in adult, critically ill trauma patients. Plasma was generated from whole blood samples collected within the first 3days of hospital admission. CAT was used to determine lag time, thrombin peak, time to thrombin peak, endogenous thrombin potential (ETP), and velocity index in plasma samples from patients, and in control samples of platelet-poor, pooled normal plasma.


RESULTS
There were 35 trauma patients and 35 controls included in this pilot analysis. Patients were a mean (SD) age of 45 (19) years, and 23 (66%) were male. The most common mechanism of injury was motor vehicle crash followed by falls, and the median (IQR) injury severity score was 17 (12-27). Three patients (8.6%) had deep vein thrombosis (DVT) confirmed by Doppler ultrasound on median hospital day 7. Compared to control samples, patients had significantly longer lag times (3.1min vs. 2.7min, p=0.02) and significantly higher ETP (1136nM∗min vs. 1019nM∗min, p=0.007), peak thrombin generation (239nM vs. 176nM, p<0.001), and velocity index (108nM/min vs. 57nM/min, p<0.001) (Fig. 1). There was no difference in the time to peak thrombin generation between the two groups (5.5min vs. 5.7min, p=0.22). In the 3 patients with VTE compared to controls, lag times were shorter and velocity index was higher while ETP and peak thrombin generation were similar. There were no statistically significant differences in thrombin generation parameters in patients with or without VTE, but lag time was numerically shorter, and thrombin peak, time to peak and area-under-the-curve (ETP) were numerically lower in patients with DVT.


CONCLUSIONS
We observed a thrombin generation profile in critically ill trauma patients consistent with an early hypercoagulable state; however, thrombin generation parameters did not discriminate patients with VTE.
Department of Pharmacotherapy and Translational Research, University of Florida College of Pharmacy, 1225 Center Drive, HPNP Bldg., Room 3315, P.O. Box 100486, Gainesville, FL 32610-0486, United States. Electronic address: svoils@cop.ufl.edu.
Stacy A
SA
Voils
Clinical Pharmacy Specialist, Surgical Critical Care, UF Health Shands Hospital, United States. Electronic address: lemosj@shands.ufl.edu.
Stephen J
SJ
Lemon
Department of Surgery, UF Health Shands Hospital, United States. Electronic address: Janeen.Jordan@surgery.ufl.edu.
Janeen
J
Jordan
Diagnostica Stago Inc., Parsippany, NJ, United States. Electronic address: paul.riley@us.stago.com.
Paul
P
Riley
Department of Pharmacotherapy and Translational Research, University of Florida College of Pharmacy, United States. Electronic address: frye@cop.ufl.edu.
Reginald
R
Frye
D000328:Adult; D000368:Aged; D001777:Blood Coagulation; D001780:Blood Coagulation Tests; D016638:Critical Illness; D005260:Female; D006801:Humans; D015601:Injury Severity Score; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013917:Thrombin / Q000378:metabolism*; D054556:Venous Thromboembolism / Q000097:blood / Q000209:etiology* / Q000378:metabolism; D020246:Venous Thrombosis / Q000097:blood / Q000209:etiology / Q000378:metabolism; D014947:Wounds and Injuries / Q000097:blood / Q000150:complications* / Q000378:metabolism
D013917:Thrombin
Calibrated automated thrombogram; Thrombin; Trauma; Venous thromboembolism