Table 1.
Baseline characteristics of included studies
| Study author and year | Study design | patients TXA/placebo | TXA dose | Male (%) | Mean or median age in years TXA/placebo | Enrollment time after trauma | Inclusion criteria | Exclusion criteria |
|---|---|---|---|---|---|---|---|---|
| Roberts et al. 2019 | Multisite RCT | 6406/6331 | 1 g TXA bolus followed by 1 g TXA maintenance | TXA: 3742 (80%) placebo: 3660 (80%) | TXA: 41.7 (19) placebo: 41.9 (19) | 2 h |
(1) Adults with TBI within 3 h of injury (2) GCS ≤ 12 or any intracranial bleeding on CT scan |
Major extracranial bleed |
| Rowell et al. 2020 [13] | Multisite RCT | 657/309 | Bolus-Maintenance arm: 1 g TXA bolus followed by 1 g TXA. Bolus only arm: 2 g TXA bolus followed by a placebo infusion | Bolus-Maintenance: 227 (73%) Bolus-Only: 255 (74%) placebo: 233 (75%) |
Bolus-Maintenance arm: 39(26–57) Bolus Only arm: 40(26–56) Placebo arm: 36(25–55) |
2 h |
(1) GCS ≤ 12 (2) Prehospital SBP ≥ 90 (3) Age ≥ 15 years (or weight ≥ 50 kg if age is unknown) |
(1) GCS = 3 with unreactive pupil (2) CPR by EMS prior to randomization (3) Burns (4) Pregnancy |
| Mahmood et al. 2021 [14] | Multisite RCT | 884/883 | 1 g TXA bolus followed by 1 g TXA maintenance | TXA: 701 (79%) placebo: 712 (81%) | TXA: 45 (29–64) placebo: 45 (29–63) | 3 h | (1) Adults with head injury who were within 3 h of injury; (2) Glasgow Coma Score (GCS) of ≤ 12; (3) any intracranial bleeding on CT, and no significant extracranial bleeding | significant extracranial bleeding |
| van Wessem et al. 2021 [15] | Single site RCT | 120/114 | 1 g TXA bolus followed by 1 g TXA maintenance | TXA: 80 (67%) placebo: 77 (68%) | TXA: 42 (23–59) placebo: 53 (33–65) | 1 h | TBI (AIS head ≥ 3) who were admitted to the adult ICU | AIS head scores based on isolated C-spine injuries |
| Mojallal et al. 2020 [16] | Single site RCT | 56/44 | 1 g TXA bolus followed by 1 g TXA maintenance | TXA: 40 (71.4%) placebo: 40 (90.9%) | N/A | 8 h | (1) age > 18. (2) detection of cerebral hemorrhage in brain CT scan (3) passage of less than 8 h after trauma incidence (4) negative history of taking anticoagulants (5) negative history of blood coagulation system impairments | patients who underwent craniotomy less than 24 h |
| Mousavinejad et al. 2020 [17] | Single site RCT | 20/20 | 1 g TXA bolus followed by 1 g TXA maintenance | TXA: 6 (30%) placebo: 8 (40%) | 55 ± 19/55 ± 18 | 8 h |
(1) ≥ 18 years within 8 h of injury (2) TBI on brain CT with no significant epidural hemorrhage (3) The need for surgery |
(1) Pregnancy (2) Coagulopathy (3) Massive transfusion and/or fresh frozen plasma (FFP) |
| Yutthakasemsunt et al. 2013 [18] | Single site RCT | 120/118 | 1 g TXA bolus followed by 1 g TXA maintenance | TXA: 103 (86%) placebo: 107 (91%) | 35 (16)/ 34 (15) | 8 h |
(1) Age ≥ 16 years (2) Moderate to severe TBI (GCS) 4 to 12 (3) Had a CT brain within 8 h (4) No immediate indication for surgery |
(1) Immediate need for surgery (2) Coagulopathy (3) Known to be receiving a medication that affects hemostasis (4) Pregnancy |
| Fakharian et al. 2017 | Single site RCT | 78/78 | 1 g TXA bolus followed by 1 g TXA maintenance | TXA: 67 (90.5) placebo: 6 688) | 42 ± 18/39 ± 18 | 8 h |
(1) Age ≥ 15 years (2) Non-penetrating injury and any kind of Traumatic ICH (3) Arrived at the hospital within 8 h 4) No need for brain surgery during the first 8 h |
(1) Major organ damage (2) Pregnancy (3) Receiving any medication that disturbs homeostasis (4) Coagulopathy |
| Jokar et al. 2017 [19] | Single site RCT | 40/40 | 1 g TXA bolus followed by 1 g TXA maintenance | TXA: 32 (40.0%) placebo: 28 (35.0%) | 35 ± 15/ 36 ± 145 | 2 h |
(1) TBI patients aged 15 years and more (2) Within 2 h of injury onset (3) Acute ICH (volume of less than 30 ml) based on CT scan findings |
(1) GCS < 8 (2) Need for surgery (3) Cerebral edema with midline shift (4) Coagulation disorders (5) Pregnancy (6) History or current VTE |
| Ebrahimi et al. 2019 [20] | Single site RCT | 40/40 | 1 g TXA bolus followed by 1 g TXA maintenance | SDH-TXA: 17 (85%) SDH-placebo: 17 (85%) EDH-TXA: 16 (80%) EDH-placebo: 18 (90%) |
SDH: 40 ± 18/40 ± 18 EDH: 24 ± 7/25 ± 7 |
8 h |
(1) Adults within 8 h of injury (2) Isolated SDH or EDH requiring surgery |
(1). Major extracranial bleeding (2) Massive transfusion (3) Coagulopathy (4) Pregnancy |
| Perel et al. 2012 [21] | Multisite RCT | 133/137 | 1 g TXA bolus followed by 1 g TXA maintenance | TXA: 111 (84.0) placebo: 117 (85.0) | 36.2 (14.0)/37.0 (13.7) | 8 h |
1) Fulfills the inclusion criteria for the CRASH-2 trial (2) GCS ≤ 14 (3) Baseline clinical CT scan consistent with TBI |
(1) Pregnancy and (2) Patients for whom a second brain CT scan was not possible |
| Bossers et al. 2021 [22] | Multisite RCT | 693/1134 |
1 g TXA bolus followed by 1 g TXA maintenance: 615 > 2 g TXA bolus: 4 |
TXA: 486 (70%) placebo: 797 (70%) | 47 (25–66)/45 (22–65) | N/A | 1) severe TBI, GCS ≤ 8 2) suspected rather than confirmed TBI because prehospital treatment, including administration of tranexamic acid | 1) BRAIN-PROTECT database who were not transported to a participating trauma center (no follow-up data were available) 2) undergoing prehospital traumatic cardiopulmonary resuscitation (inherently very high mortality, regardless of treatment) |
| Chakroun et al. 2018 | Single site RCT | 96/84 | 1 g TXA bolus followed by 1 g TXA maintenance | TXA: 88 (91.7%) placebo: 797 (70%) | 44 ± 20/39 ± 18 | 8 h | (1) age > 18. (2) intracranial bleeding in the first or the second brain CT-scan (3) a delay of management in the study center under 24 h after trauma | 1) significant extra cranial bleeding 2) TXA can improve outcome |
RCT Randomized-controlled trial, TXA Tranexamic acid, GCS Glasgow coma scale, GOS Glasgow outcome scale, TBI Traumatic brain injury, SDH Subdural hemorrhage, EDH Epidural hemorrhage, ICH Intracranial hemorrhage, N/A Not applicable