Outcomes of tranexamic acid administration in military trauma patients with intracranial hemorrhage: a cohort study

Abstract

Background: Tranexamic acid (TXA) may be a useful adjunct for military patients with severe traumatic brain injury (TBI). These patients are often treated in austere settings without immediate access to neurosurgical intervention. The purpose of this study was to evaluate any association between TXA use and progression of intracranial hemorrhage (ICH), neurologic outcomes, and venous thromboembolism (VTE) in TBI. Methods: This was a retrospective cohort study of military casualties from October 2010 to December 2015 who were transferred to a military treatment facility (MTF) in the United States. Data collected included: demographics, types of injuries, initial and interval head computerized tomography (CT) scans, Glasgow Coma Scores (GCS), and six-month Glasgow Outcome Scores (GOS). Results were stratified based on TXA administration, progression of ICH, and VTE. Results: Of the 687 active duty service members reviewed, 71 patients had ICH (10.3%). Most casualties were injured in a blast (80.3%), with 36 patients (50.7%) sustaining a penetrating TBI. Mean ISS was 28.2 ± 12.3. Nine patients (12.7%) received a massive transfusion within 24 h of injury, and TXA was administered to 14 (19.7%) casualties. Patients that received TXA had lower initial reported GCS (9.2 ± 4.4 vs. 12.5 ± 3.4, p = 0.003), similar discharge GCS (13.3 ± 4.0 vs. 13.8 ± 3.2, p = 0.58), and a larger improvement between initial and discharge GCS (3.7 ± 3.9 vs. 1.3 ± 3.1, p = 0.02). However, there was no difference in mortality (7.1% vs. 7.0%, p = 1.00), progression of ICH (45.5% vs. 14.7%, p = 0.09), frequency of cranial decompression (50.0% vs. 42.1%, p = 0.76), or mean GOS (3.5 ± 0.9 vs. 3.8 ± 1.0, p = 0.13). Patients administered TXA had a higher rate of VTE (35.7% vs. 7.0%, p = 0.01). On multivariate analysis, however, TXA was not independently associated with VTE. Conclusions: Patients that received TXA were associated with an improvement in GCS but not in progression of ICH or GOS. TXA was not independently associated with VTE, although this may be related to a paucity of patients receiving TXA. Decisions about TXA administration in military casualties with ICH should be considered in the context of the availability of neurosurgical intervention as well as severity of extracranial injuries and need for massive transfusion.

Tranexamic Acid in Aneurysmal Subarachnoid Hemorrhage: A Meta-analysis of Randomized Controlled Trials

“…Contrary to other RCTs [39][40][41][42], Chakroun et al demonstrated that TXA increased the incidence of pulmonary embolism in patients with traumatic brain injury [43]. Another retrospective study of 687 wounded soldiers showed that TXA did increase the risk of venous thrombosis [44]. In contrast, a metaanalysis of 30,522 patients in 7 clinical RCTs showed that, despite no statistical difference, the incidence of vascular occlusion in the TXA group was lower than that in the control group [45].…”

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

“…Two RCTs 2,13 were rated as good quality with low risk, whereas there was some concern with 4 RCTs. 3,4,14,15 Nine observational studies 22,23,25,[27][28][29][30]37,40 had a high risk of bias, mainly owing to inadequate handling of confounders, specifically relevant differences in baseline characteristics between intervention and control groups. All results of the meta-analysis are shown in the forest plots in Figure 1, Figure 2, and eFigures 2 to 27 in the Supplement.…”

“…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…”

“…(Figure 2). With the exception of 7 observational studies, 16,17,27,29,31,38,40 all studies had reported thromboembolic events. 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.…”

Fibrinolysis in Traumatic Brain Injury: Diagnosis, Management, and Clinical Considerations

“…77 In the context of military-related TBI with concomitant ICH, TXA has been associated with greater GCS improvement between admission and discharge, although no difference in ICH progression, long-term neurologic outcome, or mortality was observed. 78 However, a meta-analysis examining ICH progression in moderate or severe TBI suggests that TXA may decrease ICH progression in this patient population. [79][80][81] Overall, support for the use of TXA in TBI has continued to increase, highlighting the essential role of the fibrinolytic system in TBI.…”