TY - JOUR
T1 - 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)
T2 - A Randomized, Double-Blind, Placebo-Controlled, Single-Center Trial
AU - for the TAMPITI Investigators
AU - Spinella, Philip C.
AU - Thomas, Kimberly A.
AU - Turnbull, Isaiah R.
AU - Fuchs, Anja
AU - Bochicchio, Kelly
AU - Schuerer, Douglas
AU - Reese, Stacey
AU - Coleoglou Centeno, Adrian A.
AU - Horn, Christopher B.
AU - Baty, Jack
AU - Shea, Susan M.
AU - Meledeo, M. Adam
AU - Pusateri, Anthony E.
AU - Levy, Jerrold H.
AU - Cap, Andrew P.
AU - Bochicchio, Grant V.
N1 - Funding Information:
See Supplementary Acknowledgments for TAMPITI Investigators. The authors would like to acknowledge Jessica Smith, M.D., who served as the Research Monitor, as well as the Data and Safety Monitoring Board members: Enyo Ablordeppey, M.D., M.P.H., James Fehr, M.D., Philip Miller, George Despotis, M.D., Melanie Fields, M.D., and Kevin Ward, M.D. Lastly, the authors would also like to thank Dr. Amanda Staudt for help with statistical analyses. Funding. Funding was provided by the United States Department of Defense, United States Army Medical Research and Materiel Command (award W81XWH-14-1-0373), the Department of Surgery at Washington University in St. Louis, St. Louis, MO, United States, the Department of Pediatrics, Washington University in St. Louis, St. Louis, MO, United States, and by the U.S. Army Institute of Surgical Research at Joint Base San Antonio-Fort Sam Houston, San Antonio, TX, United States.
Publisher Copyright:
© Copyright © 2020 Spinella, Thomas, Turnbull, Fuchs, Bochicchio, Schuerer, Reese, Coleoglou Centeno, Horn, Baty, Shea, Meledeo, Pusateri, Levy, Cap and Bochicchio.
PY - 2020/9/8
Y1 - 2020/9/8
N2 - 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: www.ClinicalTrials.gov, identifier NCT02535949.
AB - 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: www.ClinicalTrials.gov, identifier NCT02535949.
KW - hemostasis
KW - immunology
KW - monocyte activation
KW - tranexamic acid
KW - trauma
UR - http://www.scopus.com/inward/record.url?scp=85091444197&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2020.02085
DO - 10.3389/fimmu.2020.02085
M3 - Article
C2 - 33013880
AN - SCOPUS:85091444197
SN - 1664-3224
VL - 11
JO - Frontiers in Immunology
JF - Frontiers in Immunology
M1 - 2085
ER -