eTable. Complete list of the included studies on survival, neurological outcome, and thromboembolic risk*1.
| Reference | Design | Main patient characteristics | Outcome*2 | Complication*3 | ||
|---|---|---|---|---|---|---|
| absolute | relative | absolute | relative | |||
| Knudson et al. 2022 (4) | Prospective cohorts n = 7880 Risk factors for posttraumatic TE | 18- to 40-year-old trauma patients | DVT | |||
| OR 2.49 [1.80; 3.43] | ||||||
| PE | ||||||
| OR 3.96 [1.92; 8.13] | ||||||
| van Wessem et al. 2022 (5) | Prospective cohorts n = 234 Prehospital TXA vs. placebo | Trauma with severe TBI (SBP ≤90 mm Hg); 98% blunt trauma | Mortality (overall) | |||
|
27% vs. 22%;
RD + 5%; p = 0.45 |
||||||
| Mortality (SBP on arrival ≤90 mm Hg) | ||||||
|
43% vs. 20%;
RD + 23%; p = 0.18 |
||||||
| El-Menyar et al. 2022 (1) | RCT n = 220 TXA pre- and in-hospital vs. prehospital only | 85% blunt trauma | 24-hour mortality | TE | ||
| 0.9% vs. 0.9% | RR 1.00 [0.24; 4.02] | 2.7% vs. 1.8%; RD + 0.9% | RR 1.206 [0.58; 2.49] | |||
| 28-day mortality | ||||||
| 9.1% vs. 4.5%; RD + 4.6% | RR 1.36 [0.93; 2.00] | |||||
| Ageron et al. 2022 (7) | Secondary analysis of CRASH-2 and CRASH-3 n = 32 944 TXA vs. placebo | Trauma with/without TBI | Mortality (all-cause; TXA <3 hrs) | TE (overall) | ||
| 5.7% vs. 7.2%; RD − 1.5% | OR 1.28 [1.15; 1.42] | 1.6% vs. 1.8%; RD − 0.2% | OR 0.88 [0.74; 1.04] | |||
| Mortality (severely injured; TXA <3 hrs) | TE (severely injured) | |||||
| 14.5% vs. 17.5%; RD − 3% | OR 1.25 [1.10; 1.42] | 2.9% vs. 3.0%; RD − 0.1% | OR 0.97 [0.77; 1.23] | |||
| Mortality (severely injured; TXA <1 hr) | ||||||
| OR 1.27 [1.03; 1.56] | ||||||
| Mortality (severely injured; TXA 1-3 hrs) | ||||||
| OR 1.24 [1.05; 1.46] | ||||||
| Mortality (severely injured; TXA > 3 hrs) | ||||||
| OR 1.14 [0.90; 1.45] | ||||||
| Spinella et al. 2022 (8) | Secondary analysis of TAMPITI n = 149
TXA 4 g vs. 2 g vs. placebo |
~ 80% penetrating injury | TE | |||
| 32% vs. 26.5% vs. 12% | 2 g: HR 3.20 [1.12; 9.11] 4 g: HR 5.33 [1.94; 14.63] | |||||
| Huang et al. 2022 (15) | Meta-analysis 13 RCTs n = 18 675 TXA vs. placebo | SHT | Mortality (overall) | TE | ||
| 19.8% vs. 20.8%; RD − 1% | RR 0.99 [0.92; 1.06] | 2.3% vs. 1.9%; RD + 0.4% | RR 1.05 [0.83; 1.33] | |||
| GOS score <4 (unfavorable outcome) | ||||||
| 58.7% vs. 57.8%; RD + 0.9% | RR 0.96 [0.82; 1.11] | |||||
| Germans et al. 2023 (16) | Meta-analysis 11 RCTs n = 2717 TXA vs. placebo | Aneurysmal SAH | Poor neurological outcome | |||
| 41.5% vs. 40.5%; RD + 1.0% | RR 1.03 [0.94; 1.13] | |||||
| Xiong et al. 2023 (17) | Meta-analysis 25 RCTs n = 20 146 TXA vs. placebo | ICH | Mortality (ICH) | |||
| 20.7% vs. 20.4%; RD + 0.3% | OR 1.02 [0.84; 1.23] | |||||
| ICH: mRS ≤2 (favorable outcome) | ||||||
| 30.7% vs. 29.6%; RD + 1.1% | OR 1.05 [0.89; 1.24] | |||||
| Mortality (SAH) | DVT (SAH) | |||||
| 27.8% vs. 28.3%; RD − 0.5% | OR 0.84 [0.54; 1.31] |
1.8% vs. 1.7%:
RD + 0.1% |
OR 1.08 [0.51; 2.30] | |||
| Mortality (TBI) | PE (TBI) | |||||
| 16.5% vs. 16.7%; RD + 0.2% | OR 0.91 [0.69; 1.21] | 0.6% vs. 0.6% | OR 1.22 [0.45; 3.27] | |||
| Deeb et al. 2023 (9) | Secondary analysis of PAMPer and STAAMP n = 1504
Risk of death per minute delay and prehospital vs. in-hospital |
86% blunt trauma | 24-hour mortality | |||
| + 1.5% per minute delay | aOR 1.01 [1.00; 1.02] | |||||
| 24-hour mortality (prehospital) | ||||||
| aOR 0.42 [0.21; 0.83] | ||||||
| 24-hour mortality (in-hospital) | ||||||
| aOR 0.58 [0.19; 1.75] | ||||||
| 30-day mortality | ||||||
| + 2% per minute delay | aOR 1.02 [1.00; 1.03] | |||||
| Biffi et al. 2023 (18) | Meta-analysis
5 RCTs n = 34 882 TXA prehospital vs. placebo |
Trauma with/ without TBI | 24-hour mortality (overall) | |||
| RR 0.83 [0.74; 0.95] | ||||||
| 28-day mortality (overall) | ||||||
| RR 0.93 [0.88; 0.97] | ||||||
| 28-day mortality (with TBI) | ||||||
| RR 0.96 [0.89; 1.03] | ||||||
| 28-day mortality (with TBI and severe hemorrhage) | ||||||
| RR 0.72 [0.49; 1.05] | ||||||
| PATCH-Trauma Investigators et al. 2023 (2) | RCT n = 1310 TXA prehospital vs. placebo | >90% blunt trauma | GOS-E score ≥5
(favorable outcome) and AIS head <2 |
TE | ||
| 70.2% vs. 66.1%; RD + 4.1% | RR 1.06 [0.96; 1.18] | 23.6% vs. 19.7%; RD + 3.9% | RR 1.20 [0.97; 1.48] | |||
| GOS-E score ≥5
(favorable outcome) and AIS head >2 |
||||||
| 35.4% vs. 38.2% RD − 2.8% | RR 0.93 [0.73; 1.18] | |||||
| 24-hour mortality | ||||||
| 9.7% vs. 14.1%; RD − 4.4% | RR 0.69 [0.51; 0.94] | |||||
| 28-day mortality | ||||||
| 17.3% vs. 21.8%; RD − 4.5% | RR 0.79 [0.63; 0.99] | |||||
| 6-month mortality | ||||||
| 19.0% vs. 22.9%; RD − 3.9% | RR 0.83 [0.67; 1.03] | |||||
| Acharya et al. 2023 (19) | Meta-analysis
3 RCTs n = 3081 TXA prehospital vs. placebo |
> 80% blunt trauma | GOS-E score ≥5 (favorable outcome) | TE | ||
| 56.8% vs. 55.6%; RD + 1.2% | RR 1.00 [0.93; 1.09] | 12.8% vs. 12.6%; RD + 0.2% | RR 1.04 [0.72; 1.49] | |||
| 24-hour mortality | ||||||
| 7.2% vs. 9.7%; RD − 2.5% | RR 0.73 [0.56; 0.96] | |||||
| 28-day mortality | ||||||
| 14.2% vs. 16.9%; RD − 2.7% | RR 0.82 [0.69; 0.97] | |||||
| Gunn et al. 2024 (10) | Subgroup of the prospective A CIT-2 trial n = 525 TXA 1 g bolus vs.
1 g + 1 g infusion vs. 2 g or. 2× 1 g |
59% blunt trauma | 24-hour mortality | VTE | ||
| 10% vs. 6% vs. 11%; p = 0.51 | OR 1.72 [0.41; 7.13] vs. 1 vs. 1.17 [0.25; 5.41] | 4% vs. 8% vs. 7%; p = 0.31 | OR 0.75 [0.26; 2.18] vs. 1 vs. 1.07 [0.33;
3.47] |
|||
| 28-day mortality | ||||||
| 21% vs. 21% vs. 21% | ||||||
| Song et al. 2024 (20) | Meta-analysis 10 RCTs n = 10 954 TXA vs. placebo | TBI | Mortality | PE | ||
| 17.5% vs. 19.1%; RD − 1.6% | RR 0.92 [0.85; 1.0] |
0.7% vs. 0.5%;
RD + 0.2% |
RR 1.33 [0.56; 3.15] | |||
| Mazzei et al. 2024 (11) | Secondary analysis of 2 RCTs n = 1744 TXA prehospital vs. placebo | ~90% blunt trauma | 28-day mortality | VTE | ||
| 10.5% vs. 12.1%; RD − 1.6% | HR 0.72 [0.54; 0.96] | 3.8% vs. 3.6%; RD + 0.2% | OR 1.10 [0.66; 1.86] | |||
| Fouche et al. 2024 (21) | Meta-analysis
7 RCTs n = 32 832 TXA vs. placebo |
Trauma with/ without TBI
*corrected according to information provided by Francsois Fouche |
28-day mortality (overall) | TE | ||
|
RD − 1.7% [- 2.4;
- 0.7]*; NNT 61 [42; 135] |
OR 0.89 [0.84; 0.95] | OR 0.96 [0.73; 1.27] | ||||
| 24-hour mortality (overall) | ||||||
| OR 0.76 [0.65; 0.88] | ||||||
| 28-day mortality (TBI) | ||||||
| RD − 1.3% [−2.80; 0.3]*; NNT 78 [36; 317] | OR 0.92 [0.84; 1.02] | |||||
| 28-day mortality (trauma) | ||||||
| RD − 1.7% [−2.5; −0.7]*; NNT 61 [40; 147] | OR 0.88 [0.82; 0.94] | |||||
| 28-day mortality (TXA in-hospital) | ||||||
| RD − 1.4% [−2.4; −0.6]*; NNT 70 [42; 159] | OR 0.91 [0.85; 0.96] | |||||
| 28-day mortality (TXA prehospital) | ||||||
| RD − 3.1% [−5.1; −0.7]*; NNT 33 [20; 148] | OR 0.78 [0.64; 0.95] | |||||
| Yassi et al. 2024 (3) | RCT n = 201 TXA vs. placebo | ICH | 90-day mortality | TE | ||
| 18% vs. 15%;
RD + 3% [- 4; + 13] |
aOR 1.61 [0.65; 3.98] | 3% vs. 1%;
RD + 2% [- 2%; 6%] |
||||
| 7-day mortality | ||||||
| 8% vs. 8%;
RD 0% [- 6; 7] |
aOR 1.08 [0.35; 3.35] | |||||
| mRS <3 (favorable outcome) | ||||||
| 30% vs. 32%; RD − 2% | aOR 0.77 [0.38; 1.56] | |||||
| Zhang et al. 2024 (22) | Meta-analysis 11 RCTs n = 11 299 TXA vs. placebo | TBI | Mortality (overall) | TE | ||
| 17.6% vs. 19.0%; RD − 1.4% | RR 0.93 [0.86; 1.00] | 2.0% vs. 2.1%; RD − 0.1% | RR 0.85 [0.68;1.06] | |||
| GOS score ≤4 (unfavorable outcome) | ||||||
| 32.1% vs. 30.6%; RD + 1.5% | RR 0.92 [0.78; 1.09] | |||||
| Tran et al. 2024 (23) | Meta-analysis
30 RCTs and cohorts n = 1 981 946 Risk factors for posttraumatic VTE |
Various types of injury | VTE | |||
| OR 2.84 [1.58;5.11] | ||||||
| Chen et al. 2024 (24) | Meta-analysis 2 RCTs + 9 cohorts n = 11 259 TXA prehospital vs. control | Predominantly blunt trauma | 24-hour mortality | TE | ||
| 10.06% vs. 11.97%; RD − 1.91% | OR 0.82 [0.71;0.94] | 8.1% vs. 6.7%; RD + 1.4% | OR 1.22 [1.03;1.44] | |||
| Rowell et al. 2024 (12) | Subgroup of the RCT “prehospital TXA for TBI” n = 966 TXA prehospital 1 g + 1 g infusion vs. prehospital 2 g vs. placebo | TBI | 28-day mortality | TE | ||
|
26% vs. 17% vs.
27% |
adjusted difference with ICH:
1 g + 1 g vs. placebo: 0.7 [- 7.2; 8.5] 2 g vs. placebo: −8.5 [−15.9; −1.0] 2 g vs. 1 g + 1 g: −10.2 [−17.6; −2.9] |
6% vs. 13% vs.
14% |
||||
| 24-hour mortality | ||||||
| 6% vs. 4% vs. 12% | ||||||
| GOS-E score <4 (unfavorable outcome) | ||||||
| with ICH: 53% vs. 45% vs. 50% without ICH: 11% vs. 20% vs. 19% | adjusted difference with ICH:
1 g + 1 g vs. placebo: 3.8 [−5.3; 13.0] 2 g vs. placebo: −4.6 [−13.7; 4.6] 2 g vs. 1 g + 1 g: −8.4 [−17.5; 0.7] |
|||||
| Li et al.
2025 (25) |
Meta-analysis
5 multi-center RCTs + 5 multi-center cohorts + 2 single-center cohorts n = 12 682 prehospital TXA vs. no TXA |
Trauma patients | 24-hour mortality | VTE | ||
| 9.6% vs. 11.9%; RD − 2.3% | OR 072 [0.54; 0.94] | 8.0% vs. 6.9%; RD + 1.1% | OR 1.14 [0.98; 1.33] | |||
| 28-day mortality | ||||||
| 19.8% vs. 21.0%; RD − 1.2% | OR 0.92 [0.74; 1.14] | |||||
| mortality (overall) | ||||||
| 21.7% vs. 23.4%; RD − 1.7% | OR 0.91 [0.82; 1.01] | |||||
| Osawa et al. 2025 (13) | Secondary analysis CRASH-2 and CRASH-3 n = 28 448;
TXA vs. no TXA |
Trauma with/ without TBI | 24-hour mortality (GCS score <9 or TXA <2 hours | |||
| 4.2% vs. 5.8%; RD − 1.5% [−0.87; −2.2] | RR 0.73 [0.64; 0.84] | |||||
| 24-hour mortality (all others) | ||||||
| 1.6% vs. 1.3%; RD + 0.34% [+ 0.80; −0.11] | RR 1.27 [0.94; 1.72] | |||||
| Lee et al. 2025 (26) | Meta-analysis 25 RCTs n = 16 677 TXA vs. no TXA | TBI | Mortality (overall) | TE | ||
|
RR 0.96
[0.91; 1.03] |
RR 1.11 [0.97; 1.28] | |||||
| TE (TXA > 8 hrs) | ||||||
| RR 1.16 [1.02; 1.33] | ||||||
| 30-day mortality | TE (TXA > 1 day) | |||||
|
RR 0.92
[O.84; 1.O1] |
RR 1.22 [1.03; 1.44] | |||||
| Utsumi et al. 2025 (27) | Meta-analysis 10 RCTs n = 11 237 TXA vs. no TXA | TBI | Mortality (TXA <3 hours) | TE | ||
| Placebo vs. 1 g bolus + 1 g/8 hours: | ||||||
| RR 1.1O [1.OO; 1.21] | RR 1.26 [0.69; 2.30] | |||||
| Placebo vs. 2 g bolus: | ||||||
| RR 1.66 [1.11; 2.46] | RR 0.87 [0.30; 2.52] | |||||
| 1 g bolus + 1 g/8 hours vs. 2 g bolus: | ||||||
| RR 1.51 [1.O1; 2.24] | RR 0.69 [0.23; 2.04] | |||||
| Steiner et al. 2025 (28) | Meta-analysis
8 RCTs n = 3061 TXA vs. placebo |
Stroke due to spontaneous ICH | 90-day mortality | TE | ||
| 19.1% vs.
19.1% |
OR 1.00 [0.83; 1.20] | 4.7% vs. 4.0%; RD + 0.7% | OR 1.18 [0.82; 1.68] | |||
| 7-day mortality | ||||||
| 8.6% vs. 10.3%; RD − 1.7 | OR 0.82 [0.63; 1.07] | |||||
| Bayer et al. 2025 (6) | TR-DGU cohort study n = 37 342 TXA vs. placebo | >95% blunt trauma | VTE | |||
| 5.5% vs. 2.3%; RD + 3.2% | 1× TXA: aOR 1.56 [1.35; 1.81] p <0 .001;
2× TXA: aOR 1.79 [1.43; 2.24] p < 0.001; 3× TXA: aOR 1.50 [0.91; 2.48] |
|||||
| Lin et al. 2025 (29) | Meta-analysis 1 RCTs + 9 cohorts n = 6759 TXA vs. placebo | Pediatric trauma cases | Mortality | TE | ||
| aOR 0.58 [O.38; O.89] | OR 1.01 [0.32; 3.24] | |||||
| Bian et al. 2025 (30) | Meta-analysis 10 RCTs + 6 cohorts n= 15015 TXA vs. placebo | Isolated TBI | 28-day mortality (GCS score ≥9) | |||
| RR 0.71 [0.60; 0.85] | ||||||
| 28-day mortality (GCS score ≥9) | ||||||
| RR 1.05 [0.93; 1.19] | ||||||
| Ali et al. 2026 (14) | Secondary analysis of PATCH-Trauma trial n = 1287 TXA vs. placebo | 28-day mortality | TE | |||
| 17% vs. 22%; RD − 5% | aRR 0.78 [O.64; O.95] | 24% vs. 20%; RD + 4% | aRR 1.21 [O.98; 1.49] | |||
*1
Always TXA versus control. The primary outcome is printed in bold.
*2
RR or OR [95% CI]
*3
Incidence and RR or OR [95% CI]
AIS, Abbreviated Injury Scale; aOR, adjusted odds ratio; aRR, adjusted relative risk; GCS, Glasgow Coma Scale;
GOS, Glasgow Outcome Scale (higher scores reflect better overall recovery; a score of 4 indicates a favorable outcome, defined as moderate neurological disability);
GOS-E, Glasgow Outcome Scale – Extended (higher scores reflect better overall recovery; a score of 4 indicates a favorable outcome, defined as moderate neurological disability); HR, hazard ratio; ICH, intracranial hemorrhage; CI, confidence interval; PE, pulmonary embolism;
mRS, modified Rankin Scale (higher scores reflect worse outcomes; a score of 3 indicates that the patient requires assistance with daily activities); n; sample size;
NNT, number needed to treat; OR, odds ratio; pats., patients; RCT, randomized controlled trial; RD, risk difference; RR, relative risk; SAH, subarachnoid hemorrhage;
SBP, systolic blood pressure; TBI, traumatic brain injury; TE, thromboembolism; TR-DGU TraumaRegister of the German Society for Trauma Surgery;
DVT, deep vein thrombosis; TXA, tranexamic acid; vs., versus; VTE venous thromboembolism