Tranexamic acid in life-threatening military injury and the associated risk of infective complications

Abstract

Background Tranexamic acid (TXA) has been shown to reduce mortality from severe hemorrhage. Although recent data suggest that TXA has anti-inflammatory properties, few analyses have investigated the impact of TXA on infectious complications in trauma patients. We examined the association between TXA administration and infection risk among injured military personnel. Methods Patients administered TXA were matched by injury severity score to patients who did not receive TXA. Conditional logistic regression was used to examine risk factors associated with infections within 30 days. A Cox proportional analysis evaluated risk factors in a time-to-first infection model. Results A total of 335 TXA recipients were matched to 626 patients not administered TXA. A greater proportion of TXA recipients had an infection compared to the comparative group (P <0.001). The univariate analysis estimated an unadjusted odds ratio (OR) of 2.5 (95 per cent confidence interval [CI]: 1.8–3.4) for the association of TXA with infection risk; however, upon multivariable analysis, TXA administration was not significant (OR: 1.3; CI: 0.8–1.9). Blast injuries, intensive care unit (ICU) admission, and receipt of ≥10 units of blood within 24 hours post-injury were independently associated with infection risk. The Cox proportional model confirmed association with ICU admission and blood transfusions. Moreover, traumatic amputations were also significantly associated with a reduced time-to-first infection. Conclusion In life-threatening military injuries matched for injury severity, TXA recipients did not have a higher risk for infections nor was time to developed infections shorter than in non-recipients. Extent of blood loss, blast injuries, extremity amputations, and intensive care stay were associated with infections.

Early Infections Complicating the Care of Combat Casualties from Iraq and Afghanistan

“…Another possible modification is decreasing the number of red blood cell transfusions by using post-injury tranexamic acid, an anti-fibrinolytic agent that has been shown to decrease mortality in bleeding trauma patients [40,41], or using younger blood products or blood product alternatives. It is not clear if any of these interventions would affect infection rates, however, one retrospective analysis that compared military trauma patients who did and did not receive tranexamic acid reported no significant association between tranexamic acid and infection risk [42].…”

Is Coagulopathy an Appropriate Therapeutic Target During Critical Illness Such as Trauma or Sepsis?

“…Later, et al showed that in patients undergoing cardiac surgery, patients receiving TXA and EACA showed less upregulation of pro-inflammatory genes and more upregulation of anti-inflammatory genes relative to patients not receiving these medications (95); however, they found no effects on cytokine or growth factor concentrations (96). Lewis and colleagues examined this issue retrospectively in military trauma patients; their results demonstrated no increased risk for infection, and further showed no decrease in time to infection in patients receiving TXA relative to those who had not, suggesting that early immune suppression in TXA-treated patients is not present (97). The ongoing Tranexamic Acid Mechanisms and Pharmacokinetics in Traumatic Injury (TAMPITI) trial is specifically focused on downstream immune effects following TXA administration, and should shed more light on this issue (98).…”

Mortality and Thrombosis in Injured Adults Receiving Tranexamic Acid in the Post-CRASH-2 Era

“…There were 13 retrospective studies,16–21,23–25,27,30,31,33 five prospective observational studies,22,26,28,29,32 and one randomized controlled trial 34. Ten studies22–26,29–32,34 reported administering TXA as given in the CRASH-2 trial (1 gram [g] intravenous [IV] bolus followed by 1 g IV over eight hours); three studies16,20,21 reported giving TXA 1 g bolus (without the maintenance dose), and six studies17–19,27,28,33 did not report TXA dosing. Three studies17,27,34 administered TXA within eight hours from the time of injury (as done in the CRASH-2 trial), 12 studies16,18,21–26,29–32 administered TXA primarily within three hours from the time of injury, and four studies19,20,28,33 did not report the timing of TXA administration.…”