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Three Part Question

If all [adults over the age of 65 years] [received tranexamic acid for every traumatic presentation] within the pre-hospital setting, rather than [adhering to the JRCALC indications only], would [morbidity reduce]?

Clinical Scenario

As we are aware, trauma to elderly patients is significantly worse in terms of outcome compared to a younger adult. I wanted to investigate if the benefit would out weigh the risk for administering tranexamic acid to all 'silver trauma' patients.

Search Strategy

EBSCO on the world wide web. Dates from 2000- present.
Elderly OR aged OR older OR geriatric AND
tranexamic acid OR txa AND
trauma OR silver trauma AND
morbidity OR mortality

haemorrhage/*complicataions
vascular diseases/*etiology

Search Outcome

15 results, majority relevant to the question.
Mixture of systemic reviews, RCTs and journal articles.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Erramouspe, P. J., Garcia-Pintos, M. F., Benipal, S., et al. March 2022 California, America.	Adults over 18 years who had been involved in a traumatic incident and received tranexamic acid.	Related to the CRASH-2 trial, this one trauma centre carried out an independant study to assess in 28 days the mortality and thromboembolic events after the traumatic incident and having received tranexamic acid. Excluded criteria- >8 hours since injury, elective patients, nontrauma related presentations and patients in cardiac arrest.	Mortality	The overall mortality was 12.8% (95% confidence interval [CI] = 8.9% to 16.7%)	Unclear how many of the patients who had a thromboembolic event, then subsequently died. Only conducted in one independant trauma centre- could argue not big enough or why not include more centres for a more accurate results. However, 273 patients included in the trial and it lasted for 3 years approx and that sample size suggests adequate results should be evident. Heavily relates to CRASH-2, could be room for bias. Only 61% of patients received the 2 bolus' of tranexamic acid and the other 39% received 1 bolus- arguably they should have been the same dosages to reduce bias behaviour and unjust results. Due to the nature of the trial and the variety of the trauma included, patients undergoing surgery could be at a higher risk of thromboembolisms as not specific which what type of trauma.
			thromboembolic events	The acute thromboembolic events was 6.6% (95% CI = 3.7% to 9.5%)
Manoukian, M. A. C., Tancredi, D., Nishijima, D. K. Dec 2021 America	Adults categorised into age groups who had been involved in a traumatic incident within a maximum time frame of 3 hours.	Trauma is known to be a major cause of mortality to older adults. In relation to the CRASH-2 study, the effect of tranexamic acid was investigated, specifically the heterogeneity effect from patient age.	Heterogeneity (age)	Heterogeneity evaluated using Akaike and Bayesian information criteria to determine the optimum logistic regression model and Chi-square test then evaluated statistical significance. Heterogeneity of tranexamic acid treatment did not have significant results (p = 0.11).	They provide a median age of 30 years old, however the actual age range was 14-96 and specifically because they want to concentrate on the effects related to age, the median age does not support this. Heavy lean on CRASH-2- data extracted from it therefore could face bias as results already produced from that trial. Categorised patient ages into; <26 years, 46-55years and >55years. Considering there was aged >96 there should have been another age bracket, at least >65 years in relation to elderly/ silver trauma concerns.
			Mortality	95% confidence intervals for mortality. Inparticular for considering 'silver trauma' the results proved >55 years decrease of 5.3%, 95% CI 0.4 to 10.3.
Pealing, L., Perel, P., Prieto-Merino, D. et al. Dec 2012 America	20,127 trauma patients from CRASH-2 included.	The study wanted to investigate if there was a link between population and physiological presentations in relation to risks of vascular events. The risk of death was also discussed and was the mortality rate linked with the vascular event of the original trauma/ haemorrage.	Venous event	204 patients with a PE or DVT or both. p<0.02 in relation to the clinical risk factors of a vascular event (GCS/ BP, RR etc). 123 patients with PE, 61 DVT and 20 had both.	No patient age category given, only states adult which suggests to the reader >18 years but we know in CRASH-2 there was younger. Older aged patients and blunt traumatic injuries were stated to increase chances of vascular events but no age group/ data provided to support this. Population and physiological specifics could have been further expanded on. However its detailed in order to reduce diagnositic bias this information was not provided. Not much information on tranexamic acid as personally required.
			Arterial event	200 patinets with an MI or CVA or both. 77 had an MI, 110 had a CVA and 13 had both.
			Mortality	81 deaths due to vascular event. 29 deaths from an MI, 13 from a CVA and 39 from a PE. Patients who died from Haemorrhage had a p<0.001 for a vascular event.

Comment(s)

Discussing such a complex topic with a wide variety of variables, it has to be clear what is being serached for. With specific interest in patients age, if they had receievd tranexamic acid and if not, why not and the mortality associated with the trauma or the vascular event. Patients age was visiable to breakdown in most studies to specify the age bracket for the purpose of the personal question as the statistical purpose is normally required. Having tables/ formats evident made this easier for the reader to evaluate. Prior to researching, tranexamic acid had little cautions for administering and obvious indications in the pre-hospital setting; hence the question however to learn about vascular events once hospitalised is a learning point. The research evident on the administration of tranexamic acid in trauma is extensive but linking it to an elderly aged population defines the outcomes some what. The reading regarding mortality was of interest and related to the question, the results evident where relatively small numbers in comparison to the study numbers but of high relevance.

Clinical Bottom Line

To conclude, there is not enough evidence to suggest all patients over the age of 65 years should receive tranexamic acid in every traumatic presentation in the pres-hospital setting. The risk of a thromboembolic event is evident and the balance between the two appears relevant and therefore no changes should be advocated at this time.

References

1. Erramouspe, P. J., Garcia-Pintos, M. F., Benipal, S., et al. Mortality and complication rates in adult trauma patients receiving tranexamic acid: a single-centre experience in the post CRASH-2 era. Academic Emergency Medicine 2022; 353-441.
2. Manoukian, M. A. C., Tancredi, D., Nishijima, D. K. Effect of age on the efficiency of tranexamic acid: An analysis of heterogeneity of treatment effect within the CRASH-2 dataset. ELSEVIER Dec 2021
3. Pealing, L., Perel, P., Prieto-Merino, D. et al. Risk factors for vascular occlusive events and death due to bleeding in trauma patients; an analysis of the CRASH-2 cohort. PLoS ONE 2012; 7(12)