Safety and Efficacy of Hospital Utilization of Tranexamic Acid in Civilian Adult Trauma Resuscitation

Abstract

Introduction: Patients with trauma-induced coagulopathies may benefit from the use of antifibrinolytic agents, such as tranexamic acid (TXA). This study evaluated the safety and efficacy of TXA in civilian adults hospitalized with traumatic hemorrhagic shock. Methods: Patients who sustained blunt or penetrating trauma with signs of hemorrhagic shock from June 2014 through July 2018 were considered for TXA treatment. A retrospective control group was formed from patients seen in the same past five years who were not administered TXA and matched based on age, gender, Injury Severity Score (ISS), and mechanism of injury (blunt vs penetrating trauma). The primary outcome of this study was mortality measured at 24 hours, 48 hours, and 28 days. Secondary outcomes included total blood products transfused, hospital length of stay (LOS), intensive care unit LOS, and adverse events. We conducted three pre-specified subgroup analyses to assess outcomes of patients, including (1) those who were severely injured (ISS >15), (2) those who sustained significant blood loss (≥10 units of total blood products transfused), and (3) those who sustained blunt vs penetrating trauma. Results: Propensity matching yielded two cohorts: the hospital TXA group (n = 280) and a control group (n = 280). The hospital TXA group had statistically lower mortality at 28 days (1.1% vs 5%, odds ratio [OR] [0.21], (95% confidence interval [CI], 0.06, 0.72)) and used fewer units of blood products (median = 4 units, interquartile range (IQR) = [1, 10] vs median=7 units, IQR = [2, 12.5] for the hospital TXA and control groups, respectively, (95% CI for the difference in median, -3 to -1). There were no statistically significant differences between groups with regard to 24-hour mortality (1.1% vs 1.1%, OR = 1, 95% CI, 0.20, 5.00), 48-hour mortality (1.1% vs 1.4%, OR [0.74], 95% CI, 0.17, 3.37), hospital LOS (median= 9 days, IQR = (5, 16) vs median =12 days IQR = (6, 22.5) for the hospital TXA and control groups, respectively, 95% CI for the difference in median = (-5 to 0)), and incidence of thromboembolic events (eg, deep vein thrombosis, pulmonary embolism) during hospital stay (0.7% vs 0.7% for the hospital TXA and control group, respectively, OR [1], 95% CI, 0.14 to 7.15). We conducted subgroup analyses on patients with ISS>15, patients transfused with ≥10 units of blood products, and blunt vs penetrating trauma. The results indicated lower 28-day mortality for ISS>15 (1.8% vs 7.1%, OR [0.23], 95% CI, 0.06 to 0.81) and blunt trauma (0.6% vs 6.3%, OR [0.09], 95% CI, 0.01 to 0.75); fewer units of blood products for penetrating trauma (median = 2 units, IQR = (1, 8) vs median = 8 units, IQR = (5, 15) for the hospital TXA and control groups, respectively, 95% CI for the difference in median = (-6 to -3)), and ISS>15 (median = 7 units, IQR = (2, 14) vs median = 8.5 units, IQR = (4, 16) for the hospital TXA and control groups, respectively, 95% CI for the difference in median, -3 to 0). Conclusion: The current study demonstrates a statistically significant reduction in mortality after TXA administration at 28 days, but not at 24 and 48 hours, in patients with traumatic hemorrhagic shock.

The impact of prehospital tranexamic acid on mortality and transfusion requirements: match-pair analysis from the nationwide German TraumaRegister DGU®

“…These large sample sizes were identical in terms of demographics and injury severity. The sample sizes of the propensity score-based matched-pairs analysis were up to 8 times larger than prior reported studies [ 31 – 33 ], reaching a fifth of the patients included in CRASH 2 [ 20 ]. Therefore, the findings add knowledge to the ambiguous data on prehospital TXA use in developed countries.…”

Association of Tranexamic Acid Administration With Mortality and Thromboembolic Events in Patients With Traumatic Injury

“…However, the meaningfulness of these possibly distorted results is questionable, and their impact on heterogeneity when pooling data for overall mortality needs to be considered. Information on age, sex, or ISS was missing in several RCTs 2,13,14 and observational studies [16][17][18]35,40 ; their impact on heterogeneity is thus unknown. Moreover,…”

“…Twelve studies 3,14,19,[21][22][23][24][25]30,32,33,37 revealed higher and 8 studies 2,4,13,18,20,28,36,39 revealed lower incidences of thromboembolic events for tranexamic acid treatment compared with the control cohort. Three studies 26,34,35 could not find any association (RR, 1.00) between tranexamic acid administration and thromboembolic events. It was not possible to resolve heterogeneity through the analysis of RCTs only (I 2 = 59%; P = .03).…”

“…Twenty-one studies [2][3][4]13,15,16,[20][21][22][24][25][26]28,[30][31][32][34][35][36][37]39 had reported lower mortality and 9 studies 14,17,19,23,27,29,33,38,40…”

The impact of prehospital TXA on mortality among bleeding trauma patients: A systematic review and meta-analysis

“…A number of studies have previously demonstrated that early administration of TXA either in prehospital care or ED could significantly reduce mortality in different time points (6 hours to 28 days). 36,37 We have deliberately avoided direct comparison with ED studies as time of administration is an uncontrolled variable across the two clinical arenas. The evidence from both CRASH-2 and WOMAN trials show TXA efficacy decreases over time and by 90 minutes may be of reduced benefit.…”