Evaluation of Military Use of Tranexamic Acid and Associated Thromboembolic Events

Abstract

Importance: Since publication of the CRASH-2 and MATTERs studies, the US military has included tranexamic acid (TXA) in clinical practice guidelines. While TXA was shown to decrease mortality in trauma patients requiring massive transfusion, improper administration and increased risk of venous thromboembolism remain a concern.

Objective: To determine the appropriateness of TXA administration by US military medical personnel based on current Joint Trauma System clinical practice guidelines and to determine if TXA administration is associated with venous thromboembolism.

Design, setting, and participants: This cohort study of US military casualties in US military combat support hospitals in Afghanistan and a single US-based tertiary military treatment facility within the continental United States was conducted from 2011 to 2015, with follow-up through initial hospitalization and readmissions.

Exposures: Data collected for all patients included demographic information as well as Injury Severity Score; receipt of blood products, TXA, and/or a massive transfusion; and admission hemodynamics.

Main outcomes and measures: Variance from guidelines in TXA administration and venous thromboembolism. Tranexamic acid overuse was defined as a hemodynamically stable patient receiving TXA but not a massive transfusion, underuse was defined as a patient receiving a massive transfusion but not TXA, and TXA administration was considered delayed when given more than 3 hours after injury.

Results: Of the 455 identified patients, 443 (97.4%) were male, and the mean (SD) age was 25.3 (4.8) years. A total of 173 patients (38.0%) received a massive transfusion, and 139 (30.5%) received TXA in theater. Overuse occurred in 18 of 282 patients (6.4%) and underuse in 46 of 173 (26.6%) receiving massive transfusions, and delayed administration was found in 6 of 145 patients (4.3%) receiving TXA. Overuse increased at 3.3% per quarter (95% CI, 4.0-9.9; P < .001; R2 = 0.340) and underuse decreased at -4.4% per quarter (95% CI, -4.5 to -3.6; P < .001; R2 = 0.410). Tranexamic acid administration was an independent risk factor for venous thromboembolism (odds ratio, 2.58; 95% CI, 1.20-5.56; P = .02).

Conclusions and relevance: Military medical personnel decreased missed opportunities to appropriately use TXA but also increased overuse. In addition, TXA administration was an independent risk factor for venous thromboembolism. A reevaluation of the use of TXA in combat casualties should be undertaken.

Figure 1.. Flowchart of Patients

Flowchart of patients included in the study and grouping based on variations in tranexamic acid (TXA) administration with venous thromboembolism (VTE) rates for each group.

Figure 2.. Changes in Rate of Overuse Over Time

The rates are calculated as the number of overuses divided by the total number of patients cared for in our cohort within that period. Each data point is weighted by the number of patients cared for during that period; greater size indicates a higher number of patients. The line indicates results of linear regression. The slope of the regression is 0.033x − 65.6; R² = 0.340.

Figure 3.. Changes in Rate of Underuse Over Time

The rates are calculated as the number of underuses divided by the total number of patients cared for in our cohort within that period. Each data point is weighted by the number of patients cared for during that period; greater size indicates a higher number of patients. The line indicates the results of fitted values. The slope of the fitted values is −0.044x + 89.2; R² = 0.410.