Tranexamic Acid
Original Date: 08/2011 | Supersedes: 2014 | Last Review Date: 01/2021
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 (moderate and severe)
- 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:
- Any transfusion requirement
- Risk of significant hemorrhage
- Radiographically confirmed traumatic brain injury (moderate and severe)
- The argument for empiric TXA administration: TEG may accurately identify the most severe forms of hyperfibrinolysis but are largely 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:
- DO NOT USE TXA IF 3 HOURS OR MORE AFTER INJURY.
TXA dosing is based upon indication:
- For traumatic brain injury:
- Infuse 1 gram of tranexamic acid in 100 ml of 0.9% NS over 10 minutes intravenously (more rapid injection has been reported to cause hypotension).
- Infuse a second 1-gram dose intravenously in 100 ml of 0.9% NS over 8 hours.
- For hemorrhage
- 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 Strategy
| Search | Database | Search Term | Limits | Total Yield of Articles: | # Excluded Articles | # Included Articles |
|---|---|---|---|---|---|---|
| 1 | PubMed | “tranexamic acid” and “trauma” | Randomized Controlled Trial, English | 61 | 51 | 5 |
| 2 | PubMed | “tranexamic acid” and “trauma” | Systematic Review, English | 44 | 35 | 9 |
| TOTAL | 105 | 86 | 14 | |||
| Exclude Multiples 0 | ||||||
| Included Papers 14 (5 RCTs, 9 SRs) + 2 additional papers cited (1 RCT, 1 SR) |
||||||
Literature:
| Systematic Reviews | |||
|---|---|---|---|
| Author/Year | Intervention | Conclusions | Comments |
| Yokobori, 2020 (1) | 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 (2) | TXA in TBI patients | Mortality: RR 0.92 (95% CI 0.88–0.97) | N=30,442 Included 5 RCTs |
| Morales-Cane, 2019 (3) | TXA in trauma | Mortality: RR 0.89 (05% CI 0.83–0.96) | N=20,697 Included 4 RCTs |
| El-Menyar, 2019 (4) | Prehospital TXA | Reduction in 24 hour mortality. | Included 2 observational studies. |
| Poole, 2016 (5) | TXA | Recommend TXA. | Only included CRASH-2 |
| Ker, 2015 (6) | TXA | Recommend TXA. | Included CRASH-2 and Yutthakasemunt 2013 |
| Zehtabchi, 2014 (7) | 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 (8) | TXA | Reduction in mortality and no evidence of complications. | Only included CRASH-2. |
| Roberts, 2011 (9) | TXA | Reduction in mortality and no evidence of complications. | Only included CRASH-2. |
| Randomized Controlled Trials | |||
|---|---|---|---|
| Author | Inclusion/Outcome | Results | Comments |
| Rowell, 2020 (10) | 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 (11) | 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 (12) | 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. | |||
| Smaller RCTs | |||
| Fakharian, 2018 (13) | 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 (14) | 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 |
| A Caution on Viscoelastic Hemostatic Assay Based TEG Strategy | |
|---|---|
| Author | Comments |
| Cardenas, 2014 (15) | -75% of patients with moderate fibrinolysis had a LY30 ≤2.4 -50% of patients with severe fibrinolysis had a LY30 ≤2.1 |
| Raza, 2013 (16) | ->90% of fibrinolytic activity was not detected with ROTEM definition of hyperfibrinolysis (ML>15%) -6 in 10 patients showed evidence of moderate fibrinolytic activity but only 1 in 20 showed ROTEM hyperfibrinolysis |
| In sum, VHA may accurately identify the most severe forms of hyperfibrinolysis but are largely insensitive to lower levels of fibrinolytic activity, which may be clinically significant. | |
References:
- Yokobori S, Yatabe T, Kondo Y, Kinoshita K. Efficacy and safety of tranexamic acid administration in traumatic brain injury patients: a systematic review and meta-analysis. Journal of intensive care. 2020;8:46.
- July J, Pranata R. Tranexamic acid is associated with reduced mortality, hemorrhagic expansion, and vascular occlusive events in traumatic brain injury – meta-analysis of randomized controlled trials. BMC neurology. 2020;20(1):119.
- Morales-Cane I, Lopez-Soto PJ, Rodriguez-Borrego MA. Tranexamic acid in trauma patients in the emergency department: systematic review and meta-analysis. Emergencias : revista de la Sociedad Espanola de Medicina de Emergencias. 2019;31(4):261-9.
- El-Menyar A, Sathian B, Asim M, Latifi R, Al-Thani H. Efficacy of prehospital administration of tranexamic acid in trauma patients: A meta-analysis of the randomized controlled trials. The American journal of emergency medicine. 2018;36(6):1079-87.
- Poole D, Cortegiani A, Chieregato A, Russo E, Pellegrini C, De Blasio E, et al. Blood Component Therapy and Coagulopathy in Trauma: A Systematic Review of the Literature from the Trauma Update Group. PloS one. 2016;11(10):e0164090.
- Ker K, Roberts I, Shakur H, Coats TJ. Antifibrinolytic drugs for acute traumatic injury. The Cochrane database of systematic reviews. 2015(5):Cd004896.
- Zehtabchi S, Abdel Baki SG, Falzon L, Nishijima DK. Tranexamic acid for traumatic brain injury: a systematic review and meta-analysis. The American journal of emergency medicine. 2014;32(12):1503-9.
- Roberts I, Shakur H, Ker K, Coats T. Antifibrinolytic drugs for acute traumatic injury. The Cochrane database of systematic reviews. 2012;12:Cd004896.
- Roberts I, Shakur H, Ker K, Coats T. Antifibrinolytic drugs for acute traumatic injury. The Cochrane database of systematic reviews. 2011(1):Cd004896.
- Rowell SE, Meier EN, McKnight B, Kannas D, May S, Sheehan K, et al. Effect of Out-of-Hospital Tranexamic Acid vs Placebo on 6-Month Functional Neurologic Outcomes in Patients With Moderate or Severe Traumatic Brain Injury. Jama. 2020;324(10):961-74.
- Investigators C-. Effects of tranexamic acid on death, disability, vascular occlusive events and other morbidities in patients with acute traumatic brain injury (CRASH-3): a randomised, placebo-controlled trial. Lancet. 2019;394(10210):1713-23.
- Shakur H, Roberts I, Bautista R, Caballero J, Coats T, Dewan Y, et al. Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant hemorrhage (CRASH-2): a randomised, placebo-controlled trial. Lancet. 2010;376(9734):23-32.
- Fakharian E, Abedzadeh-Kalahroudi M, Atoof F. Effect of Tranexamic Acid on Prevention of Hemorrhagic Mass Growth in Patients with Traumatic Brain Injury. World neurosurgery. 2018;109:e748-e53.
- Jokar A, Ahmadi K, Salehi T, Sharif-Alhoseini M, Rahimi-Movaghar V. The effect of tranexamic acid in traumatic brain injury: A randomized controlled trial. Chin J Traumatol. 2017 Feb;20(1):49-51. doi: 10.1016/j.cjtee.2016.02.005. Epub 2017 Jan 20. PMID: 28209450; PMCID: PMC5343096.
- Cardenas JC, Matijevic N, Baer LA, Holcomb JB, Cotton BA, Wade CE. Elevated tissue plasminogen activator and reduced plasminogen activator inhibitor promote hyperfibrinolysis in trauma patients. Shock. 2014;41(6):514-21.
- Raza I, Davenport R, Rourke C, Platton S, Manson J, Spoors C, et al. The incidence and magnitude of fibrinolytic activation in trauma patients. Journal of thrombosis and haemostasis : JTH. 2013;11(2):307-14.