Overview for healthcare professionals

Tranexamic acid is an antifibrinolytic agent used to prevent, stop or reduce unwanted bleeding. It can be administered by injection or taken orally as a tablet. Following trauma it is administered as an intravenous bolus injection followed by an 8-hour infusion.

Regulatory status of tranexamic acid

When tranexamic acid is used in major trauma, it is being used off-label because it does not currently have UK marketing authorisation for the prophylaxis and treatment of significant haemorrhage following trauma. In line with the guidance from the General Medical Council (GMC), it is the responsibility of the prescriber to determine the clinical need of the patient and the suitability of using tranexamic acid outside its authorised indications.

Tranexamic acid is available for oral and intravenous administration: these preparations differ in their licensed indications. Tranexamic acid injection (Cyclokapron, Pfizer) is a prescription-only medicine licensed in the UK for administration as a slow intravenous injection for short-term use in[1]:

  • prophylaxis and treatment in patients at high risk of pre- and post-operative haemorrhage following:

    • prostatectomy

    • conisation of the cervix

    • surgical procedures and dental extractions in people with haemophilia

  • haemorrhage complications in association with thrombolytic therapy

  • haemorrhage associated with disseminated intravascular coagulation with predominant activation of the fibrinolytic system.

Evidence statements

  • A large high-quality international RCT found that administration of tranexamic acid reduces mortality in patients with or at risk of significant haemorrhage following trauma[2].

  • A health economic analysis has found that tranexamic acid for the prevention and treatment of significant haemorrhage in trauma patients has an incremental cost of $64 international dollars (£43) per life saved[3].

  • An exploratory analysis of the trial data indicates that overall benefit may apply only to people treated within 3 hours of injury[4].

Summary of the evidence

This section gives a brief summary of the main evidence. A more thorough analysis is given in the Evidence Review section.

Efficacy

The main evidence published to date comes from the CRASH-2 study[2], a large, high-quality international randomised controlled trial (RCT) which is relevant to UK practice. This recruited 20,211 adult trauma patients with or at risk of significant haemorrhage in whom treatment could commence within 8 hours of when the injury occurred. They were randomised to receive a 1 g loading dose of tranexamic acid infused intravenously over 10 minutes followed by a further 1 g infused over 8 hours, or placebo.

CRASH-2 showed that a short course of intravenous tranexamic acid given to trauma patients with, or at risk of, significant bleeding increases survival without an increased risk of adverse events (see table 1).

Table 1: Summary of the CRASH-2 trial

Tranexamic acid

Placebo

Analysis

CRASH-2[2]

Modified ITT groupa

n=10060

n=10067

Primary outcomeb

14.5%

16.0%

RR 0.91, 95% CI 0.85 to 0.97, p=0.0035

Death due to bleeding

4.9%

5.7%

RR 0.85, 95% CI 0.76 to 0.96, p=0.0077

Vascular occlusionc

0.3%

0.5%

RR 0.69, 95% CI 0.44 to 1.07, p=0.096

Primary outcome by estimated time from injuryd

<1 hour

509/3747 (13.6%)

581/3704 (15.7%)

RR 0.87, 99% CI 0.75 to 1.00d

>1 hour to ≤3 hours

463/3037 (15.2%)

528/2996 (17.6%)

RR0.87, 99% CI 0.75 to 1.00d

>3 hours

491/3272 (15.0%)

502/2262 (14.9%)

RR 1.00, 99% CI 0.86 to 1.17d

Abbreviations: CI, confidence interval; ITT, intention to treat; n, number of patients; RR, relative risk

a 20,211 patients were randomised. 3 patients in the tranexamic acid group and 1 patient in the placebo group withdrew consent. Primary outcome data were not available for 33 patients in the tranexamic acid group and 47 patients in the placebo group. Analysis is based on the remaining 20127 patients (99.6% of those randomised)

b All cause in-hospital mortality within 4 weeks of injury

c Includes myocardial infarction, stroke, and pulmonary embolism

d Note that these results are given with 99% confidence intervals. A subsequent analysis found that tranexamic acid significantly reduced the relative risk of all-cause death compared with placebo if administered within 3 hours of injury but not if administered more than 3 hours after injury (see the Evidence Review section)

In an exploratory analysis of the CRASH-2 results, early treatment (within 3 hours of injury) was found to be significantly more effective than treatment given after 3 hours[4]. Early treatment has been estimated to have the potential to save 755 life-years per 1,000 trauma patients in the UK[3].

Safety

No statistically significant increase in the risk of vascular occlusive events (including myocardial infarction, stroke and pulmonary embolism) was observed in the CRASH-2 trial[2].

Cost-effectiveness and cost

A cost-effectiveness analysis based on the results of the CRASH-2 trial found administering tranexamic acid to have an incremental cost of $64 international dollars (£43) per life saved in a variety of settings[3].

The cost of tranexamic acid at the dosage used in the trial is estimated at £6.20 per patient, excluding VAT and disposables (October 2012)[5].



[1] Electronic Medicines Compendium (eMC). Summary of Product Characteristics: Tranexamic acid. Available from www.medicines.org.uk [Accessed on 24 September 2012]

[2] CRASH-2 trial collaborators. (2010) 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 376: 23–32.

[3] Guerriero C, Cairns J, Perel P et al. (2011) Cost-effectiveness analysis of administering tranexamic acid to bleeding trauma patients using evidence from the CRASH-2 trial. PLoS one; 6(5).

[4] CRASH-2 trial collaborators. (2011) The importance of early treatment with tranexamic acid in bleeding trauma patients: an exploratory analysis of the CRASH-2 randomised controlled trial. Lancet 377: 1096–101.