Ian Roberts, Haleema Shakur-Still , Adefemi Afolabi, Christopher Hawkey et el (HALT-IT trial investigators) published a trial in Lancet comparing tranexamic acid to placebo in gastrointestinal hemorrhage.
Tranexamic acid(TXA) is known to prevent the fibrinolysis. Early use of TXA reduces surgical bleeding and death related to bleeding from traumatic injury and has reduced the burden of intracranial bleeding after head injury. This was demonstrated in CRASH 2 AND CRASH 3 TRIALS.
GASTROINTESTINAL HEMORRHAGE is a life-threatening emergency, and patient’s need urgent resuscitation with blood product transfusion and medical, surgical, or endoscopic treatment. Bennett et al (Cochrane Database Syst Rev. 2014;11:CD006640) demonstrated a reduction in all-cause mortality for 1654 patients when TXA was used for GIBs (RR 0.61; p = 0.01).
To test this hypothesis, TXA was used against placebo in gastrointestinal hemorrhage, in an international randomized double-blind placebo-controlled trial.
164 hospitals in 15 countries (UK, Pakistan, Nigeria, Egypt, Malaysia, Georgia, Romania, Nepal, Sudan, Saudi Arabia, Spain, Ireland,
Albania, Papua New Guinea, and Australia).
12,009 adult patients with upper or lower GIBs and a clinical diagnosis of significant bleeding (hypotension, tachycardia, shock, with a risk of death)
Standard TXA dose of a 1-g bolus over 10 minutes with an additional 3-g infusion at 125 mL/hr for 24 hours versus placebo.
The primary outcome was death due to bleeding within 5 days of randomisation.
Secondary outcomes were death due to bleeding within 24 h and within 28 days of randomisation, all-cause and cause-specific mortality
at 28 days, rebleeding within 24 h, within 5 days, and within 28 days of randomisation, surgery or radiological intervention, blood product transfusion, thromboembolic events (deep vein thrombosis, pulmonary embolism, stroke, and myocardial infarction), seizures, other complications (including other significant cardiac event, sepsis, pneumonia, respiratory failure, renal failure, liver failure), days in an intensive care unit,and functional status.
Death attributed to bleeding occurred in 222 (3.7%) in the TXA group versus 226 (3.8%) in the placebo group (RR 0.99; CI, 0.82-1.18). When adjusting for covariates and removing open-label TXA use, there was no difference in outcome.
When comparing death due to bleeding within 24 hours (2.1% for TXA vs. 2.0% for placebo), death within 28 days (4.2% for TXA vs. 4.4% for placebo), and death from all causes (9.5% for TXA vs. 9.2% for placebo), there existed no statistical significant difference.
The risk for thromboembolic events was overall not significant (0.4% for TXA vs. 0.3% for placebo); However, the risk of venous thromboembolic events was higher in the TXA group (0.8% vs. 0.4%; RR, 1.85; CI, 1.15 to 2.98).
Risk of seizures was higher in the TXA group (0.6% vs. 0.4%; RR, 1.73; CI, 1.03 to 2.93).
Tranexamic acid is only effective in 1st 3 hours of bleeding, and it is hard to determine the initiation time of bleeding and gastrointestinal hemorrhage. Patient presentation is often delayed. Furthermore, patients with cirrhosis have mixed picture of fibrinolysis.