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What is the role of tranexamic acid in treatment of traumatic hemorrhage?

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asked May 4, 2012 in Conditions and Treatments by Hatice Simsek MD (3,070 points)
edited Jun 4, 2012 by LarryEitel

4 Answers

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CRASH-2: tranexamic acid and trauma patients

Published March 24, 2011 [Lancet]

 

A new analysis of the 2010 CRASH-2 study shows that tranexamic acid should be given as early as possible to bleeding trauma patients; if treatment is not given until three hours or later after injury, it is less effective and could even be harmful. In this new analysis, the CRASH-2 investigators analysed subgroups of patients who had received tranexamic acid less than one hour after injury; between one and three hours after injury; or more than three hours after injury.

 

The importance of early treatment with tranexamic acid in bleeding trauma patients: an exploratory analysis of the CRASH-2 randomised controlled trial

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Findings 10,096 patients were allocated to tranexamic acid and 10,115 to placebo, of whom 10,060 and 10,067 respectively, were analysed. 1063 deaths (35%) were due to bleeding. We recorded strong evidence that the effect of tranexamic acid on death due to bleeding varied according to the time from injury to treatment (test for interaction p<0·0001). Early treatment (≤1 h from injury) signifi cantly reduced the risk of death due to bleeding (198/3747 [5·3%] events in tranexamic acid group vs 286/3704 [7·7%] in placebo group; relative risk [RR] 0·68, 95% CI 0·57–0·82; p<0·0001). Treatment given between 1 and 3 h also reduced the risk of death due to bleeding (147/3037 [4·8%] vs 184/2996 [6·1%]; RR 0·79, 0·64–0·97; p=0·03). Treatment given after 3 h seemed to increase the risk of death due to bleeding (144/3272 [4·4%] vs 103/3362 [3·1%]; RR 1·44, 1·12–1·84; p=0·004). We recorded no evidence that the eff ect of tranexamic acid on death due to bleeding varied by systolic blood pressure, Glasgow coma score, or type of injury.

 

Tranexamic acid for trauma
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Comment
 

Who, then, should be treated with tranexamic acid? Most of the 274 study sites in CRASH-2 were in low-income and middle-income countries, where other treatments directed at coagulopathy, such as fresh frozen plasma, platelets, and cryoprecipitate, are less available. Although many patients with acute coagulopathy will die before reaching hospital, tranexamic acid is a practical, affordable, and effective treatment for bleeding trauma patients in such centres, provided they receive it within 3 h of injury.

Far less clear is the place for tranexamic acid in high income countries where massive transfusion protocols incorporate fresh-frozen plasma that contains all the endogenous antifi brinolytic elements in plasma.9 Plasma can cause harm as well as benefi t, and there is little prospective evidence regarding its efficacy.  However, because it is in widespread use, and because late administration of tranexamic acid can be harmful, it is unlikely that many clinicians in major trauma centres will choose tranexamic acid as first-line treatment.

The best place for tranexamic acid in developed trauma systems might actually be in the prehospital environment. Helicopter and road transport direct to major trauma centres has reduced overall injury mortality, but has extended the time before patients

answered May 4, 2012 by Jan B. Wade (4,900 points)
edited May 6, 2012 by Jan B. Wade
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Rev Col Bras Cir. 2012;39(1):77-80.

Tranexamic acid for traumatic hemorrhage.

[Article in English, Portuguese]

Luz LDSankarankutty APassos ERizoli SFraga GPNascimento Jr B.

 

 

INTRODUCTION

Besides being directly responsible for most of the early in-hospital deaths, bleeding can also contribute to late mortality related to multiorgan failure in trauma1. Bleeding trauma patients may develop a complex and unique coagulopathy; where multiple mechanistic factors such as dilution, consumption, acidosis, hypothermia, poor fibrinogen utilization, and excessive clot breakdown (hyperfibrinolysis) are responsible for its development2.

Clot breakdown (fibrinolysis) is a normal response to surgery and trauma in order to maintain vascular patency and can become exaggerated (hyperfibrinolysis) in some cases. The antifibrinolytic drug tranexamic acid (TXA), a lysine analogue, interferes with the binding of plasminogen to fibrin, which is necessary for plasmin activation. Fibrinolysis consists of activated plamin cleaving fibrin. Antifribrinolytic drugs can prevent clot breakdown and thus reduce blood loss in surgery3. In elective surgery, TXA reduces blood transfusion by a third, without significant reduction in mortality or increased postoperative complications3. TXA has recently been shown to reduce deaths in a large population of trauma patients4.

The TBE-CiTE Journal Club performed a critical appraisal of the most important evidence recently published on the topic and provides evidence-based recommendations on the use of TXA in trauma.

TBE-CITE CONCLUSION

The conclusions reached by at the telemedicine meeting are based on 3 recent publication and a systematic review:

· The CRASH-2 study, a large placebo-controlled randomized clinical trial that included over 20.000 trauma patients;

· Its subgroup analysis; and

· The MATTERs trial, a fairly large retrospective study in combat injury including 896 patients;

· A Cochrane systematic review of the literature published in 2011, on the use of anti fibrinolytic for the treatement of traumatized patients that are bleeding9.

These 4 publications together studied over 30.000 patients and they suggest that TXA reduces mortality in civilian and military trauma patients without increasing the risk of complications. The two studies of the CRAS-2 suggest the drug should be administered in low-doses and routinely in the management of bleeding trauma patients, but only in the first 3 hours after the trauma.

TBE-CiTE Recommendation on the use of tranexamic acid for the management of traumatic bleeding

1. Tranexamic acid should be routinely used in trauma patients with evidence of bleeding;

2. Tranexamic acid should be included in transfusion protocols for trauma;

3. Tranexamic acid should be given within 3 hours of injury;

4. Administer 1g of TXA intravenously (bolus over 10 minutes) followed by the infusion of 1g over 8 hours.

http://www.ncbi.nlm.nih.gov/pubmed/22481711

 

http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-69912012000100015&lng=en&nrm=iso&tlng=en (free fulltext)

 

 

 

answered May 4, 2012 by Hatice Simsek MD (3,070 points)
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Cost-Effectiveness Analysis of Administering Tranexamic Acid to Bleeding Trauma Patients Using Evidence from the CRASH-2 Trial

READ ENTIRE ARTICLE HERE

 

Objective
 

To assess the cost effectiveness of giving tranexamic acid (TXA) to bleeding trauma patients in low, middle and high income settings.

Methods

The CRASH-2 trial showed that TXA administration reduces the risk of death in bleeding trauma patients with a small but statistically significant increase in non-intensive care stay. A Markov model was used to assess the cost effectiveness of TXA in Tanzania, India and the United Kingdom (UK). The health outcome was the number of life years gained (LYs). Two costs were considered: the cost of administering TXA and the cost of additional days in hospital. Cost data were obtained from hospitals, World Health Organization (WHO) database and UK reference costs. Cost-effectiveness was measured in international dollars ($) per LY. Both deterministic and probabilistic sensitivity analyses were performed to test the robustness of the results to model assumptions.
 

Findings
 

Administering TXA to bleeding trauma patients within three hours of injury saved an estimated 372, 315 and 755 LYs per 1,000 trauma patients in Tanzania, India and the UK respectively. The cost of giving TXA to 1,000 patients was $17,483 in Tanzania, $19,550 in India and $30,830 in the UK. The incremental cost of giving TXA versus not giving TXA was $18,025 in Tanzania, $20,670 in India and $48,002 in the UK. The estimated incremental cost per LY gained of administering TXA is $48, $66 and $64 in Tanzania, India and the UK respectively.
 

Conclusion
 

Early administration of TXA to bleeding trauma patients is likely to be highly cost effective in low, middle and high income settings.

answered May 6, 2012 by Jan B. Wade (4,900 points)
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BMJ. 2012 Sep 11;345:e5839. doi: 10.1136/bmj.e5839.

Effect of tranexamic acid on mortality in patients with traumatic bleeding: prespecified analysis of data from randomised controlled trial.

 

Abstract

OBJECTIVES:

To examine whether the effect of tranexamic acid on the risk of death and thrombotic events in patients with traumatic bleeding varies according to baseline risk of death. To assess the extent to which current protocols for treatment with tranexamic acid maximise benefits to patients.

DESIGN:

Prespecified stratified analysis of data from an international multicentre randomised controlled trial (the CRASH-2 trial) with an estimation of the proportion of premature deaths that could potentially be averted through the administration of tranexamic acid.

PARTICIPANTS:

13 273 trauma patients in the CRASH-2 trial who were treated with tranexamic acid or placebo within three hours of injury and trauma patients enrolled in UK Trauma and Audit Research Network, stratified by risk of death at baseline (<6%, 6-20%, 21-50%, >50%).

INTERVENTION:

Tranexamic acid (1 g over 10 minutes followed by 1 g over eight hours) or matching placebo.

 

 

CONCLUSIONS:

Tranexamic acid can be administered safely to a wide spectrum of patients with traumatic bleeding and should not be restricted to the most severely injured.

http://www.ncbi.nlm.nih.gov/pubmed?term=on%20behalf%20of%20the%20CRASH-2%20collaborators.%5BCorporate%20Author%5D

 

Free PMC Article

answered Sep 25, 2012 by Hatice Simsek MD (3,070 points)

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