Tranexamic Acid
Original Date: 08/2011 | Last Review Date: 08/2024
Purpose: To guide the use of tranexamic acid (TXA) after injury
Recommendations:
- TEG-guided TXA administration:
- If within 3 hours of injury, give TXA for LY30 ≥ 3% and:
- Any transfusion requirement
- Radiographically confirmed traumatic brain injury
- If within 3 hours of injury, give TXA for LY30 ≥ 3% and:
- Empiric TXA administration:
- If within 3 hours of injury, give TXA for patients with:
- MTP activation AND profound hemorrhagic shock (SBP<75mmHg)
- At faculty discretion, MTP with ongoing transfusion requirements OR radiographically confirmed traumatic brain injury (moderate and severe)
- TEG may accurately identify the most severe forms of hyperfibrinolysis but is insensitive to lower levels of fibrinolytic activity, which may be clinically significant.
- In multiple RCTs with over 30,000 patients, TXA has not been shown to increase adverse events (including VTE).
- If within 3 hours of injury, give TXA for patients with:
- Not recommended for use greater than 3 hours after injury
- Most benefit is within 1 hour of injury.
TXA Dosing:
- Infuse 2 gram of tranexamic acid in 100 ml of 0.9% NS over 10 minutes intravenously
- No follow-up maintenance dose is required.
| Search | Database | Search Term | Limits | Total Yield of Articles: | # Excluded Articles | # Included Articles |
|---|---|---|---|---|---|---|
| 1 | PubMed | “tranexamic acid” and “trauma” | Randomized Controlled Trial, English | 105 | 95 | 10 |
| 2 | PubMed | “tranexamic acid” and “trauma” | Systematic Review, English | 90 | 74 | 16 |
| TOTAL | 195 | 170 | 26 | |||
| Systematic Reviews | |||
|---|---|---|---|
| Author | Inclusion/Outcome | Results | Comments |
| Song, 2024 (1) | TXA in TBI patients, RCT only | Mortality: RR 0.92 (95% CI 0.85 to 1.00) Reduced hemorrhage growth: RR 0.78 (0.62-0.97) No difference in PE, did not look at VTE |
N=11,299 Included 10 RCTs No mention of timing of administration |
| Fouche, 2023 (2) | TXA in trauma patients, RCT only | 30-day mortality: moderate benefit, OR 0.89 (95% CI 0.84 to 0.95) 24-hour mortality: moderate benefit, OR 0.76 (0.65-0.88) Thrombotic complications: no difference |
Included 7 RCTs (CRASH-2, CRASH 3) Suggestive of better outcomes with earlier administration (<1h). Bigger benefit (OR 0.78 vs 0.91) if with out-of-hospital administration |
| Acharya, 2023 (3) | Prehospital TXA in trauma patients vs. placebo or no TXA | 24 hour mortality: RR 0.73 (95% CI 0.56-0.96) No difference 6 months “functional outcome” No difference in bleeding or clotting complications Increased risk of infection/sepsis? RR 1.17 (1.03-1.33) |
N=~476 Included 3 RCT |
| Biffi, 2022 (4) | Prehospital TXA in trauma patients (with and without TBI) compared to placebo | Mortality 24 hours: RR 0.83 (95% CI 0.74-0.95) Increasing benefit with earlier administration (<3h) No difference in adverse events |
N = 34,882 Included 5 RCT (CRASH-2, CRASH-3, STAAMP, TAMPITI, TXA) Includes children. |
| Karl, 2022 (5) | TXA in trauma patients | 24-hour mortality: not pooled due to heterogeneity 1-month mortality: RR 0.83 (95% CI 0.71-0.97) Heterogenous results with thromboembolic events |
N = 43,473 Included 31 studies Heterogeneity limits conclusions |
| Rowe, 2021 (6) | TXA in trauma patients without TBI with pre-hospital, in-hospital, or perioperative administration TXA in TBI patients, timing not specified |
Heterogenous results for mortality. No difference in complications Increased VTE with TXA in in-hospital administration, but no difference in single-dose administration |
More of a summary paper of the RCTs, confusing results. Subgroup of single-dose is good |
| Al-Jeabory, 2021 (7) | TXA in trauma patients in shock, not TBI | Survival to hospital discharge: 15.5% in TXA group vs. 16.4% in non-TXA (OR 0.81, 95% CI 0.62-1.06), in civilian subgroup was OR 0.69, 95% CI 0.51-0.93) Decrease in MI, blood products transfused |
Included 17 studies, RCT + observational |
| Almuwallad, 2021 (8) | TXA in bleeding trauma patients who got pre-hospital TXA | 24 hour mortality: OR 0.60 (95% CI 0.37-0.99) No difference at 30 days VTE: OR 1.49 (95% CI 0.90-2.46) not statistically significant but trend toward increase |
N=2347 Included 11 trials |
| Yokobori, 2020 (9) | TXA in TBI patients | Mortality: RR 0.93 (95% CI 0.85–1.01) No increase in thrombotic complications |
N=10,124 Included 7 RCTs |
| July, 2020 (10) | TXA in TBI patients | Mortality: RR 0.92 (95% CI 0.88–0.97) | N=30,442 Included 5 RCTs |
| Morales-Cane, 2019 (11) | TXA in trauma | Mortality: RR 0.89 (05% CI 0.83–0.96) | N=20,697 Included 4 RCTs |
| El-Menyar, 2019 (12) | Prehospital TXA | Reduction in 24 hour mortality. | Included 2 observational studies. |
| Poole, 2016 (13) | TXA | Recommend TXA. | Only included CRASH-2 |
| Ker, 2015 (14) | TXA | Recommend TXA. | Included CRASH-2 and Yutthakasemunt 2013 |
| Zehtabchi, 2014 (15) | TXA in TBI | Significant reduction in progression of lesion. Non-significant but large reduction in mortality and unfavorable functional status at discharge. | Included 2 RCTs. |
| Roberts, 2012 (16) | TXA | Reduction in mortality and no evidence of complications. | Only included CRASH-2. |
| Randomized Controlled Trials | |||
|---|---|---|---|
| Author | Interventions/Outcomes | Results | Comments |
| PATCH-Trauma, 2023 (17) | Inclusion: “high risk for trauma-induced coagulopathy,” COAST score ≥ 3, TXA administered within 3 hours Outcome: functional survival at 6 months (GOS-E 5-8) |
Functional survival at 6 months: 53.7% with TXA, 53.5% without TXA. 24 hour mortality: 9% vs. 14% respectively, approached statistical significance |
13% lost to follow-up No VTE or other thrombotic difference between groups. |
| Note: 2 groups – 1310 patients, roughly 650 in each group. 1) pre-hospital administration of 1g followed by in-hospital 1g IV over 8 hours, 2) placebo bolus and infusion. Trend towards improvement with earlier (<1h) administration. Maybe impacts early (<24 h) survival. No VTE or other thrombotic difference between groups. May not be applicable as they give infusion after the initial bolus. | |||
| STAAMP 2021 (18) | Inclusion: Unstable trauma patient (SBP <90, HR> 110) Intervention: pre-hospital TXA Outcome: 30-day survival |
No difference in 30-day or 24-hour mortality among groups. Only significant difference (decreased mortality) if within 1 hour of injury | No difference in VTE or thrombotic complications. |
| Note: 4 groups based on 3 phases of administration. Phase A = pre-hospital, Phase B = at hospital bolus, Phase C = 8 hour infusion. Control = placebo for all 3 phases. Abbreviated = 1g TXA (Phase A), placebo for Phase B and C. Standard = 1g TXA (Phase A), placebo (Phase B), 1g TXA (Phase C). Repeat Bolus = 1g TXA for Phase A, B, and C. | |||
| Rowell, 2020 (19) | TBI with GCS ≤12 Outcome: favorable neurologic outcome at 6 months |
Favorable outcome at 6 months with TXA – 65%; favorable outcome at 6 months with TXA – 62% (not statistically significant difference) | Thrombosis more common in 2 g bolus and placebo groups. 2 g bolus patients more likely to develop seizure |
| Note: 3 groups – 1) out-of-hospital 1g IV TXA followed by in-hospital 1 g IV over 8 hours; 2) out-of-hospital 2 g IV TXA followed by in-hospital placebo; 3) out-of-hospital and in-hospital placebo. Almost 25% of all groups had no TBI; over 40% had no intracranial hemorrhage on initial imaging (either died before imaging or no TBI). | |||
| CRASH-3, 2019 (20) | Inclusion: TBI, GCS≤12 or radiographic bleed Outcome: head injury related death in the hospital within 28 days |
TXA reduced head injury related death by 1.3% in all patients; 1.5% in patients not GCS 3; and 1.7% in mild-moderate TBI. | No difference in thrombotic complications. Placebo (n=4,553) TXA (n=4,649) |
| *Note: Intervention – 1 g IV over 10 minutes, followed by 1 g IV over 8 hours. Summary: TXA is safe in patients with TBI and treatment within 3 hours of injury reduces head injury-related death.” | |||
| CRASH-2 (21) | Inclusion: trauma patients with or at risk of bleeding Outcome: in hospital death within 4 weeks |
TXA reduced mortality by 1.5%. No difference in vascular occlusive events. |
Placebo (n=10,067) TXA (n=10,060) |
| Note: Unclear if generalizable to our trauma center. Intervention – 1 g IV over 10 minutes, followed by 1 gram IV over 8 hours. | |||
| Small RCTs | |||
| Negahi, 2022 (22) | Inclusion: injured patients in hemorrhagic shock who arrived within 3 hours Outcome: mortality, LOS, products transfused |
Poorly designed small study. Dose – 1g within 3 hours of injury, then 1g q12 for 2 more doses No difference in mortality. Lower LOS in TXA group and fewer products transfused |
No difference in thrombotic events n=68, Tehran |
| El Menyar, 2021 (Qatar) (23) | Inclusion: Injured adults who received 1g TXA pre-hospital Outcome: mortality at 24 hours, 28 days |
Randomized to receive 2nd dose at hospital vs. placebo. No significant difference in mortality at 24 hours or 28 days, and no difference in VTE events. | They use CCT not TEG Maybe no need for 2nd dose – but they didn’t specify TBI? N=220 |
| Spinella PC, 2020 (Wash U) (24) | Inclusion: Adult Level 1 trauma patients, at least 1 unit of blood transfused and/or emergent operation, able to receive TXA within 2 hours of injury Outcome: reduction in monocyte activation within 72 hours. Secondary outcome: thromboembolic events, multiple organ failure, mortality at 28 days |
Randomized to receive placebo or 2g or 4g TXA. 1 bolus dose, no infusion. No difference in decrease in monocyte activation or mortality, but increased thromboembolic events with 4g (placebo 12%, 2g 26.5%, and 4g 32.0%, p=0.05) | Goal of study was evaluate immune modulation but trauma seemed to be determining factor, not TXA. Higher doses than we use n=149 |
| Fakharian, 2018 (25) | Inclusion: TBI Outcome: progression of hemorrhage |
No significant difference in progression, though there was reduced volume of hemorrhage in the TXA group. | No difference in thrombotic complications. N = 149 |
| Jokar, 2017 (26) | Inclusion: TBI Outcome: growth of hemorrhage |
No significant difference in progression, though there was reduced volume of hemorrhage in the TXA group. | No difference in complications. N= 80 |
References:
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