Background

AUTHOR=Spinella Philip C. , Thomas Kimberly A. , Turnbull Isaiah R. , Fuchs Anja , Bochicchio Kelly , Schuerer Douglas , Reese Stacey , Coleoglou Centeno Adrian A. , Horn Christopher B. , Baty Jack , Shea Susan M. , Meledeo M. Adam , Pusateri Anthony E. , Levy Jerrold H. , Cap Andrew P. , Bochicchio Grant V. , for the TAMPITI Investigators , Enyo Ablordeppey M.D. , James Fehr M.P.H. , Philip Miller M.D. , George Despotis M.D. , Melanie Fields M.D. , Kevin Ward M.D. TITLE=The Immunologic Effect of Early Intravenous Two and Four Gram Bolus Dosing of Tranexamic Acid Compared to Placebo in Patients With Severe Traumatic Bleeding (TAMPITI): A Randomized, Double-Blind, Placebo-Controlled, Single-Center Trial JOURNAL=Frontiers in Immunology VOLUME=11 YEAR=2020 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2020.02085 DOI=10.3389/fimmu.2020.02085 ISSN=1664-3224 ABSTRACT=Background

The hemostatic properties of tranexamic acid (TXA) are well described, but the immunological effects of TXA administration after traumatic injury have not been thoroughly examined. We hypothesized TXA would reduce monocyte activation in bleeding trauma patients with severe injury.

Methods

This was a single center, double-blinded, randomized controlled trial (RCT) comparing placebo to a 2 g or 4 g intravenous TXA bolus dose in trauma patients with severe injury. Fifty patients were randomized into each study group. The primary outcome was a reduction in monocyte activation as measured by human leukocyte antigen-DR isotype (HLA-DR) expression on monocytes 72 h after TXA administration. Secondary outcomes included kinetic assessment of immune and hemostatic phenotypes within the 72 h window post-TXA administration.

Results

The trial occurred between March 2016 and September 2017, when data collection ended. 149 patients were analyzed (placebo, n = 50; 2 g TXA, n = 49; 4 g TXA, n = 50). The fold change in HLA-DR expression on monocytes [reported as median (Q1–Q3)] from pre-TXA to 72 h post-TXA was similar between placebo [0.61 (0.51–0.82)], 2 g TXA [0.57 (0.47–0.75)], and 4 g TXA [0.57 (0.44–0.89)] study groups (p = 0.82). Neutrophil CD62L expression was reduced in the 4 g TXA group [fold change: 0.73 (0.63–0.97)] compared to the placebo group [0.97 (0.78–1.10)] at 24 h post-TXA (p = 0.034). The fold decrease in plasma IL-6 was significantly less in the 4 g TXA group [1.36 (0.87–2.42)] compared to the placebo group [0.46 (0.19–1.69)] at 72 h post-TXA (p = 0.028). There were no differences in frequencies of myeloid or lymphoid populations or in classical complement activation at any of the study time points.

Conclusion

In trauma patients with severe injury, 4 g intravenous bolus dosing of TXA has minimal immunomodulatory effects with respect to leukocyte phenotypes and circulating cytokine levels.

Clinical Trial Registration