Tranexamic acid in trauma
Posted by Matthew Mac Partlin on Saturday, January 18, 2014 Under: Clinical topics
Posted by Matthew Mac Partlin on Monday, March 5, 2012
The use of Tranexamic Acid in truamatic haemorrage has been gaining increasing attention since the publication of the CRASH-II trial in 2010. Tranexamic acid (TXA) is an antifibrinolytic, meaning that it prevents the breakdown of clot that has already formed. This is different to the commonly used FFP and prothrombin complex concentrates (PCC), which provide clotting factors to facilitate clot formation and the much more expensive Factor VIIa, which promotes clot formation. TXA has also had an anti-inflamatory influence proposed.
The CRASH-II trial was a pragmatic, multicentre, prospective, randomised, placebo-controlled trial conducted in 40 (mostly developing) countries and it recruited over trauma 20,00 patients. It demonstrated a 9% all cause mortality relative risk reduction (absolute risk reduction 1.5%, NNT = 67) and a 15% haemorrhage-related mortality relative risk reduction (absolute risk reduction 0.8%, NNT = 125) at 4 weeks post injury; with no difference in blood product usage and no increased incidence in thrombotic events. The intervention was early (within 8 hours of injury) administration of TXA 1g IV over 10 minutes followed by a further 1g IV over 8 hours. ("Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial." Lancet. 2010 Jul 3;376(9734):23-32. PMID: 20554319)
The CRASH-II group subsequently performed subgroup analyses on the original study population. (Be wary of data mining when you read this kind of statement. Post hoc analyses should really be used to identify groups needing further properly randomised prospective trials.) They demonstrated that the earlier a patient received TXA the lower the Odds Ratio (OR) for haemorrhage-related mortality. The greatest benefit was shown for those who received TXA within 1 hour of injury. Those who received TXA more than 3 hours from injury had an OR confidence interval which included unity, suggesting no benefit and there is debate that there may even be risk of harm.
The original CRASH-II trial has been subjected to much criticism, particularly related to the demographics of the study population, yet it is gaining significant traction. Many hospitals have already, or are in the process of including Tranexamic acid into their trauma management protocols and guidelines. There is talk of introducing it into pre-hospital trauma management algorithms as well, particularly since the 2011 post hoc analysis. However, at present, the use of TXA for haemorrhage in severe trauma in the U.S. remains an off-label use as per the FDA.
The military have developed a keen interest in TXA and this year, there is a retrospective registry-based study reporting lower unadjusted mortality (17.4% vs 23.9%, P = .03, NNT = 76) and coagulopathy rates for injured combatants who required at least 1 unit of packed RBCs treated with TXA boluses only (i.e. no 8 hour infusion). The greatest benefit was seen in those who received a massive blood transfusion (10uPRBCs or more in 24 hours). The TXA group had a higher ISS (25.2 v 22.5) than the control group. There was a higher incidence of DVT and PE in the TXA group, but with a higher incidence of injuries associated with subsequent DVT and PE occurrence.
So, this begs the question: Should we carry tranexamic acid 1g vials to some or all of the motor sport events so as to begin an infusion in an obviously bleeding trauma victim? There are follow on questions to then consider.
These are questions that might benefit from consideration by medical advisory groups involved in motor sport clinical and safety development.
References
Interestingly, there are no guidelines for tranexamic acid usage in trauma on either the EAST group or Trauma.org websites.
The use of Tranexamic Acid in truamatic haemorrage has been gaining increasing attention since the publication of the CRASH-II trial in 2010. Tranexamic acid (TXA) is an antifibrinolytic, meaning that it prevents the breakdown of clot that has already formed. This is different to the commonly used FFP and prothrombin complex concentrates (PCC), which provide clotting factors to facilitate clot formation and the much more expensive Factor VIIa, which promotes clot formation. TXA has also had an anti-inflamatory influence proposed.
The CRASH-II trial was a pragmatic, multicentre, prospective, randomised, placebo-controlled trial conducted in 40 (mostly developing) countries and it recruited over trauma 20,00 patients. It demonstrated a 9% all cause mortality relative risk reduction (absolute risk reduction 1.5%, NNT = 67) and a 15% haemorrhage-related mortality relative risk reduction (absolute risk reduction 0.8%, NNT = 125) at 4 weeks post injury; with no difference in blood product usage and no increased incidence in thrombotic events. The intervention was early (within 8 hours of injury) administration of TXA 1g IV over 10 minutes followed by a further 1g IV over 8 hours. ("Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial." Lancet. 2010 Jul 3;376(9734):23-32. PMID: 20554319)
The CRASH-II group subsequently performed subgroup analyses on the original study population. (Be wary of data mining when you read this kind of statement. Post hoc analyses should really be used to identify groups needing further properly randomised prospective trials.) They demonstrated that the earlier a patient received TXA the lower the Odds Ratio (OR) for haemorrhage-related mortality. The greatest benefit was shown for those who received TXA within 1 hour of injury. Those who received TXA more than 3 hours from injury had an OR confidence interval which included unity, suggesting no benefit and there is debate that there may even be risk of harm.
The original CRASH-II trial has been subjected to much criticism, particularly related to the demographics of the study population, yet it is gaining significant traction. Many hospitals have already, or are in the process of including Tranexamic acid into their trauma management protocols and guidelines. There is talk of introducing it into pre-hospital trauma management algorithms as well, particularly since the 2011 post hoc analysis. However, at present, the use of TXA for haemorrhage in severe trauma in the U.S. remains an off-label use as per the FDA.
The military have developed a keen interest in TXA and this year, there is a retrospective registry-based study reporting lower unadjusted mortality (17.4% vs 23.9%, P = .03, NNT = 76) and coagulopathy rates for injured combatants who required at least 1 unit of packed RBCs treated with TXA boluses only (i.e. no 8 hour infusion). The greatest benefit was seen in those who received a massive blood transfusion (10uPRBCs or more in 24 hours). The TXA group had a higher ISS (25.2 v 22.5) than the control group. There was a higher incidence of DVT and PE in the TXA group, but with a higher incidence of injuries associated with subsequent DVT and PE occurrence.
So, this begs the question: Should we carry tranexamic acid 1g vials to some or all of the motor sport events so as to begin an infusion in an obviously bleeding trauma victim? There are follow on questions to then consider.
- Given that blood products are rarely kept at motor sport events due to logistical barriers, should tranexamic acid be given to all bleeding trauma patients in anticipation of need, or only to bleeding hypotensive and/or tachycardic patients? The trial design of CRASH-II would suggest the first strategy.
- For events such as the Melbourne Formula 1 GP, where the transport time from the scene to a major trauma centre is very short, should TXA be excluded from the kit, as there is a risk of delaying transport.
- If TXA is to be given on scene, should we limit ourselves to the administration of the 1g over 10 minute bolus, as per the MATTERs trial, or should we plan to also administer the subsequent 1g over the next 8 hours, as per the CRASH-II trial.
These are questions that might benefit from consideration by medical advisory groups involved in motor sport clinical and safety development.
References
- Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial. Lancet. 2010 Jul 3;376(9734):23-32. PMID: 20554319
- The importance of early treatment with tranexamic acid in bleeding trauma patients: an exploratory analysis of the CRASH-2 randomised controlled trial. The Lancet, Vol. 377(9771):1096-1101. PMID: 21439633
- The Trauma Professional's Blog: htp://regionstraumapro.com/post/17372835122
- Tranexamic acid for trauma patients: a critical review of the literature. J Trauma 71(1):S9-S14, 2011.
- Military Application of Tranexamic Acid in Trauma Emergency Resuscitation (MATTERs) Study. Arch Surg. 2012;147(2):113-119.
- Scott Weingart's EMCrit podcasts - Podcast 67 – Tranexamic Acid (TXA), Crash 2, & Pragmatism with Tim Coats (one of the CRASH-II investigators): http://emcrit.org/podcasts/tranexamic-acid-trauma/
- Tranexamic Acid (TXA) in Tactical Combat Casualty Care, Guideline Revision Recommendation. Committee on Tactical Combat Casualty Care, 11 August 2011 – http://emcrit.org/wp-content/uploads/2012/02/TXA-in-tac-combat-casualty-care.pdf
Interestingly, there are no guidelines for tranexamic acid usage in trauma on either the EAST group or Trauma.org websites.
In : Clinical topics
Tags: "tranexamic acid" "txa" "haemorrhage" "hemorrage" "crash 2" "crash ii" "matters"
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