Tranexamic Acid
A drug with so much evidence it has earned its own page.
Intro
Synthetic lysine analogue
Half-life: 3 hours
Urinary excretion
Mechanism
Competitively binds to the high affinity lysine binding site of plasminogen --> preventing its conversion to active plasmin. It also binds to free plasmin.
--> prevents binding of plasmin/plasminogen to fibrin clot or fibrin monomers —> preventing clot lysis.
Use
Wide ranging!
Large trials in major haemorrhage lead to TXA being placed on the WHO list of essential medicines in 2013.
TXA Trials
(History: Keio Journal 1962 First Report of TXA)
CRASH-2 2013 - >20,000 patients. Death within 4 weeks of traumatic injury was reduced by 9% vs placebo. Study lead to widespread uptake of TXA in major haemorrhage.
WOMAN 2017 - >20,000 patients. TXA for post-partum haemorrhage. 19% reduction in death, benefit time-dependent (best given within 3 hours of onset of bleeding).
ATACUS 2017 - >4500 patients. Prophylactic TXA prior to cardiac surgery. Reduced post-op bleeding events. Increased rate of post-op seizure seen (not reported in other trials)
CRASH-3 2019 - >12,000 patients. TXA within 3 hours of acute traumatic brain injury. Primary outcome was head injury related death within 28 days. Benefit seen for mild injury (GCS 9-15 and pupils reactive)
HALT-IT 2020 - 12,000 patients. No benefit from high dose TXA in acute GI bleeding. Contrasts with trials of TXA in other major haemorrhage settings, why? CRASH-2 and WOMAN showed importance of giving TXA within 3 hours of bleeding onset to achieve survival benefit - often hard to time the onset of GI bleeding, likely receiving medical attention hours after bleeding starts.
POISE-3 2022 - 9500 patients. Prophylactic use of TXA in non-cardiac surgery. Reduces bleeding events.
BJA 2022 - Analysis of TXA use by sex. In poly traume patients with matched injury severity scores, women are half as likely as men to receive TXA.
In Process (as of 2023):
WOMAN-2: TXA to prevent PPH in women with moderate to severe anaemia
IM-WOMAN: Use of intramuscular TXA (to increase access and ease of use)