Should tranexamic acid be given in paediatric trauma?
Date First Published:
December 7, 2021
Last Updated:
January 10, 2024
Report by:
Dr Josie Bradford, FY2 (Stepping Hill Hospital, Manchester, UK)
Three-Part Question:
In a [paediatric trauma patient presenting to the emergency department], does using [tranexamic acid] improve outcomes [in terms of mortality, transfusion requirements, re-bleeding rates and need for surgery]?
Clinical Scenario:
A 12-year-old child presents to the emergency department following a major trauma. Primary survey reveals signs of shock so you commence initial resuscitation for this. Tranexamic acid is widely used for adult trauma patients and you wonder if using it in this child would reduce the bleeding and improve outcomes.
Search Strategy:
A literature search was conducted using:
Medline 1964 to present via NICE Healthcare Databases
EMBASE 1974 to present via NICE Healthcare Databases
[exp *CHILD or exp *ADOLESCENT or exp *MINORS or (adolescen* OR child* OR p?ediatric*).ti,ab]
AND
[exp *”TRANEXAMIC ACID” or ("tranexamic acid" OR TXA).ti,ab]
AND
[exp *"WOUNDS AND INJURIES"/ or (trauma OR injur*).ti,ab]
AND
[exp *MORTALITY or (mortality OR death).ti,ab]
Trip Pro (date unknown) was also searched using the following search strategy:
[paediatric OR child OR pediatric OR adolescent]
AND
["tranexamic acid" OR TXA]
AND
[trauma OR injury]
AND
[reduced mortality OR death]
Medline 1964 to present via NICE Healthcare Databases
EMBASE 1974 to present via NICE Healthcare Databases
[exp *CHILD or exp *ADOLESCENT or exp *MINORS or (adolescen* OR child* OR p?ediatric*).ti,ab]
AND
[exp *”TRANEXAMIC ACID” or ("tranexamic acid" OR TXA).ti,ab]
AND
[exp *"WOUNDS AND INJURIES"/ or (trauma OR injur*).ti,ab]
AND
[exp *MORTALITY or (mortality OR death).ti,ab]
Trip Pro (date unknown) was also searched using the following search strategy:
[paediatric OR child OR pediatric OR adolescent]
AND
["tranexamic acid" OR TXA]
AND
[trauma OR injury]
AND
[reduced mortality OR death]
Outcome:
Medline: 35 papers. Of these, 4 were relevant.
EMBASE: 66 papers. Of these, 9 were relevant once de-duplicated.
Trip: 7 papers. Of these 1 was relevant but duplicated with Medline & EMBASE.
Total: 67 papers once deduplicated. Of these, 9 were relevant. The majority of excluded papers were looking at the use of TXA in paediatric surgery or following PPH and were not relevant to the aims of this BET therefore excluded.
EMBASE: 66 papers. Of these, 9 were relevant once de-duplicated.
Trip: 7 papers. Of these 1 was relevant but duplicated with Medline & EMBASE.
Total: 67 papers once deduplicated. Of these, 9 were relevant. The majority of excluded papers were looking at the use of TXA in paediatric surgery or following PPH and were not relevant to the aims of this BET therefore excluded.
Relevant Paper(s):
| Study Title | Patient Group | Study type (level of evidence) | Outcomes | Key results | Study Weaknesses |
|---|---|---|---|---|---|
| Tranexamic acid in pediatric combat trauma requiring massive transfusions and mortality Hamele et al. 2020 USA | 507 trauma patients <18 years from Iraq & Afghanistan requiring > 40ml/kg blood products in 24hrs (excluding burns & fatal head injuries) | Retrospective cohort study | In-hospital mortality | In patients requiring massive transfusions, those receiving TXA were less likely to die in hospital (8.5% vs 18.3%) although not statistically significant (p=0.055) | None of the results statistically significant although TXA reduced odds of death on logistic regression Retrospective study design can only show association not causation Limited data around dose + timing of TXA administration as well as lack of data on complications e.g. thromboembolic events + seizures Subject to survival bias i.e. those that received TXA self-selected as they remained alive to have it |
| Hospital, ventilator & ICU-free days | Similar outcomes for hospital, ventilator & ICU-free days | ||||
| Total blood product volume | Those receiving TXA had a higher 24-hr blood product administration (p.0.015) | ||||
| Tranexamic acid administration to pediatric trauma patients in a combat setting The pediatric trauma and tranexamic acid study (PED-TRAX) Eckert et al. 2014 USA | All paediatric trauma admissions to Camp Bastion, Afghanistan from 2008-2012 766 injured patients aged <18 |
Retrospective cohort study | Patient survival before discharge | TXA administration independently associated with decreased mortality among all patients OR 0.27, p=0.03 (correcting for demographics, injury type & severity, vitals & lab parameters) (p=0.03) | Relatively small sample size Retrospective study design can only show association not causation Lack of data regarding blood loss & coagulation studies to compare the effect of TXA on blood loss & coagulation 1g adult dosing administered regardless of child’s weight or age No data on TXA dose timing or subsequent dosing of TXA Limited longer-term outcome data as significant percentage transferred early after stabilisation Combat setting may not be representative of trauma in civilian setting |
| Neurologic status at discharge | Patients receiving TXA were significantly more likely to have a near-normal GCS (14-15) at discharge & less severe brain injury (GCS <9) at discharge | ||||
| Mechanical ventilation at discharge | Significantly lower percentage of patients receiving TXA requiring mechanical ventilation at discharge (6% vs 22%, p<0.01) | ||||
| 9% received TXA - usually in severe abdominal or extremity trauma | |||||
| No adverse safety/ medication related complications | |||||
| Experience in an Urban Level 1 Trauma Center With Tranexamic Acid in Pediatric Trauma: A Retrospective Chart Review Thomson et al. 2019 USA | 48 patients aged <16 admitted to a single level 1 trauma centre having MTP ordered on admission to ED or ICU | Retrospective observational analysis | Survival to hospital discharge | No difference in survival to hospital discharge in those receiving TXA vs those who didn’t (19% vs 14%, p=0.55) | Observational study design can only show association not causation Small study size & not powered May be a difference in mechanism of injury or unmeasured confounder not accounted for in analysis Only 1/3rd of patients receiving TXA received a subsequent infusion Selection bias - needing MTP so may reflect worse injury severity or haemorrhage than general trauma population Information bias – reliant on documentation of complications e.g. thrombosis |
| Surgical intervention | In group not receiving TXA went on to have surgical procedure more often (84% vs 69% but not statistically significant) | ||||
| Blood transfusion in 1st 24hrs; type & volume of blood product administered; length of hospital stay; safety based on occurrence of thrombosis | No identifiable difference between groups for blood transfusion, type of blood product administered, length of hospital stay or thrombosis | ||||
| 60% received TXA | |||||
| Safety of Tranexamic Acid During Pediatric Trauma: A Nationwide Database Study Maeda et al. 2018 Japan | 61,779 patients aged <12 admitted to hospital with diagnosis of trauma between 2010-2014 |
Retrospective cohort study Propensity matched to get 1914 pairs of patients with/without TXA |
of TXA – including seizure incidence, thromboembolic events, renal dysfunction | Proportion of seizures significantly higher in group receiving TXA (0.37% vs. 0%, p=0.008) | Retrospective study design can only show association not causation Propensity score matching may have missed unobserved confounding factors Lack of information regarding disease status & medical information e.g. use of anticoagulants & antiepileptics Lack of information on timing of TXA administration – there may be patients coded has having seizure who had this before TXA administered |
| In-hospital mortality | No significant difference between other outcomes between groups | ||||
| Efficacy and Safety of Tranexamic Acid in Civilian Pediatric Trauma Patients Receiving Transfusion Lock et al. 2021 USA | 20 patients identified by trauma registry at an academic hospital in Jan 2013. Matched by age, gender, ISS + mechanism of injury | Retrospective cohort study | In hospital mortality | No significant difference for in-hospital mortality (0% vs 6.7%, p=1.00) | Retrospective study design can only show association not causation Small cohort size No statistical significance of results Older population (median age 17) and low baseline ISS (median ISS 12) therefore results may not be applicable to general trauma population |
| Definitive bleeding control | Better in TXA group (40% vs 26.7%, p=0.61) | ||||
| Length of stay (LOS) | Reduced LOS in TXA group (6 days vs 9.1 days, p=0.83) | ||||
| Blood products required in 24hrs | Reduced in TXA group (9.8ml/kg vs 15.2ml/kg, p=0.38) | ||||
| No thromboembolic events or seizures | |||||
| Efficacy and safety of tranexamic acid in pediatric trauma patients: Evidence from meta-analysis Al-Jeabory et al. 2021 Poland | 4 studies comparing TXA vs. non-TXA treatment for paediatric trauma patients excluding articles relating to head injuries. Total of 8751 paediatric patients. | Meta-analysis | In hospital mortality | No statistical difference for in-hospital mortality in TXA vs non-TXA (1.8% vs 3.6% respectively, OR =1.77, p=0.51) | Results not statistically significant Head injuries excluded and TXA may be beneficial for this subset of trauma patients |
| Complications: seizures, thromboembolism, renal dysfunction | Increased risk of seizures with TXA administration (0.4% vs 0%, OR =15.06, p=0.06) | ||||
| Comparative risk of thromboembolism in TXA vs non-TXA (0.3% vs 0.2%, P=0.72, p=0.62) | |||||
| Comparative risk of renal dysfunction in TXA vs non-TXA (0.2% vs 0%, P=7.01, p=0.2) | |||||
| Use of Tranexamic Acid in the Paediatric Trauma Patient Booth et al. 2015 UK | 16 with traumatic injury between 2006-2013 coded as traumatic injury on joint theatre trauma registry | Retrospective cohort study | Mortality | TXA associated with higher injury severity score (ISS) + consequently overall mortality higher in this group (21.5% vs 16%, p=0.47) | Retrospective study design can only show association not causation Small cohort size High p values therefore not statistically significant |
| Sub-group analysis for injury severity score (ISS) >15 and severe TBI (GCS <5) | Lower mortality in children receiving TXA with severe TBI (24% vs 43%, p=0.06) Lower mortality in children receiving TXA with high ISS >15 (27% vs 38%, p=0.18) | ||||
| 65 cases received TXA (13.4%) | |||||
| Tranexamic Acid for Paediatric Trauma Borgman et al. 2014 UK | 4327 paediatric trauma patients without burn or fatal head trauma from defence trauma registry between 2006-2013 receiving massive transfusion (>40ml/kg) | Retrospective cohort study | In-hospital mortality | Lower overall mortality in group receiving TXA (8.5% vs 18.5%, p=0.055) | Retrospective study design can only show association not causation Small cohort size Significantly different mechanism of injury between groups therefore may be confounding results High p values therefore not statistically significant |
| 24-hour mortality | Lower 24-hr mortality in group receiving TXA (3.4% vs 6.7%, p=0.33) | ||||
| Blood products transfused | Those receiving TXA tended to receive more blood products in 1st 24hrs | ||||
| 59 cases received TXA (11.6%) | |||||
| A group had more cases of blast injury (83% vs 57%, p<0.001) whereas group not receiving TXA tended to have more blunt/ penetrating trauma | |||||
| Tranexamic acid in paediatric major trauma: a TARN data analysis 2008–2020 Thorpe et al. 2021 UK | 27,385 patients <16 from TARN data between 2008-2020 + no clinical exclusions | Retrospective analysis of TARN data | Change in prevalence of TXA use over time | TXA use increased year-on-year from 1.2% in 2012 to 10.1% in 2020 | Retrospective study design can only show association not causation No p-values therefore unclear if results statistically significant |
| Impact of change e.g., thrombotic events, blood product use, surgical intervention, evaluation of injury patterns | No change in 30-day mortality over time | ||||
| No significant increase in thrombotic complications over time | |||||
| 4.9% received TXA in total, 54.6% of these aged 12-15y/o | |||||
| RTCs (64%) + penetrating injuries (12.7%) most common mechanisms of injury in those receiving TXA | |||||
| Median ISS in those receiving TXA was 20 compared to 9 in untreated patients | |||||
| 61% of patients treated with TXA were admitted to ICU compared to 18.6% without | |||||
| Blood products were transfused in 18.2% patients receiving TXA compared to 0.4% without |
Author Commentary:
The data is inconsistent as to whether TXA offers any benefit and reduction in mortality, as well as association with complications such as seizures and VTE. All of the studies were retrospective cohort analyses and therefore cannot determine causality. Furthermore, most of the studies had a small sample size therefore unlikely to be representative of the wider population.
There is an ongoing RCT (TIC-TOC) comparing the use of TXA vs placebo. Results are expected in 2027. https://clinicaltrials.gov/ct2/show/study/NCT04387305
There is an ongoing RCT (TIC-TOC) comparing the use of TXA vs placebo. Results are expected in 2027. https://clinicaltrials.gov/ct2/show/study/NCT04387305
Bottom Line:
Although there is a wealth of evidence to suggest that TXA administration in adult trauma patients reduces mortality, there is not the same evidence for the paediatric population. The available evidence is conflicting, with some studies demonstrating a reduction in mortality whilst others show no significant difference with an increased risk of complications such as seizures and thrombosis. More research is needed to draw conclusions about the use of TXA in the paediatric trauma population. The RCPCH released a statement in 2012 advising that “TXA administration, preferably within 3 hours of trauma, for children is likely to be beneficial”. They “recommend a pragmatic dosage schedule of 15mg/kg” loading dose “over 10 minutes followed by 2mg/kg/hr.”
References:
- Hamele et al.. Tranexamic acid in pediatric combat trauma requiring massive transfusions and mortality
- Eckert et al. . Tranexamic acid administration to pediatric trauma patients in a combat setting The pediatric trauma and tranexamic acid study (PED-TRAX)
- Thomson et al.. Experience in an Urban Level 1 Trauma Center With Tranexamic Acid in Pediatric Trauma: A Retrospective Chart Review
- Maeda et al. . Safety of Tranexamic Acid During Pediatric Trauma: A Nationwide Database Study
- Lock et al.. Efficacy and Safety of Tranexamic Acid in Civilian Pediatric Trauma Patients Receiving Transfusion
- Al-Jeabory et al.. Efficacy and safety of tranexamic acid in pediatric trauma patients: Evidence from meta-analysis
- Booth et al. . Use of Tranexamic Acid in the Paediatric Trauma Patient
- Borgman et al.. Tranexamic Acid for Paediatric Trauma
- Thorpe et al.. Tranexamic acid in paediatric major trauma: a TARN data analysis 2008–2020