🚩 Tranexamic Acid - It's...
Highlights
- 🚩 Tranexamic Acid - it's complicated....
➡️It's widely used for treatment & prevention of haemorrhage
➡️It's in the WHO's List of Essential Medicines & recommended in the European Traumatic Haemorrhage guideline (2023)
➡️But is it as efficacious as we think?
🧵 1/17
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- 🚩 History
➡️Drs. Utako & Shosuke Okamoto invented TXA in 1962
➡️They identified that the amino acid lysine inhibited the degradation of plasmin, a profibrinolytic enzyme
➡️Lysine was modified to first produce Epsilon- Amino-Caproic Acid and later TXA, x 27 more potent
2/17
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- 🚩 Pharmacology
➡️TXA is a molecular analog of lysine
➡️It inhibits fibrinolysis by preventing the binding of plasminogen to fibrin
➡️This inhibits plasmin formation & displaces plasminogen from the fibrin surface
➡️It also has effects on the immune system & inflammation
3/17
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- 🚩Landmark Trials
A number of major TXA trials for acute bleeding have been published over the past 13 years, with varying results
➡️CRASH-2 & STAAMP - traumatic haemorrrhage
➡️WOMAN - Post partum haemorrhage
➡️HALT-IT - Upper GI bleeding
➡️CRASH-3 & Rowell - TBI
4/17
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- 🚩CRASH-2
➡️The landmark CRASH-2 trial was published in 2010
➡️20,211 adult trauma patients with, or at risk of, significant bleeding were randomised to TXA or placebo
➡️all-cause mortality ⬇️ by 1.5% (14.5% vs 16%)
➡️risk of death from bleeding ⬇️ by 15% (4.9% vs 5.7%)
5/17
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- 🚩STAAMP
➡️STAAMP was published in 2020
➡️903 adults at risk for hemorrhage after trauma
➡️prehospital administration of tranexamic acid or placebo
➡️30 day mortality 8.1% vs 9.9% (difference, –1.8%; 95% CI, –5.6% to 1.9%; P = 0.17)
6/17
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- 🚩Rowell Trial
➡️Published 2020
➡️1063 patients with moderate - severe TBI
➡️20 hospitals, 39 EMS in 2 countries
➡️primary outcome - favorable neurologic function at 6 months (GOSE >4)
➡️results were similar: 65% vs 62% (P = 0.84)
7/17
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- 🚩CRASH-3
➡️Published 2019
➡️12737 TBI patients
➡️175 hospitals in 29 countries
➡️primary outcome was head injury-related death in hospital within 28 days of injury in patients treated within 3 h of injury
➡️results were similar: 18.5% v 19.8% (RR 0.94; 95% CI, 0.86–1.02)
8/17
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- 🚩WOMAN
➡️Published 2017
➡️20,060 women with post-partum haemorrhage
➡️193 hospitals in 21 countries
➡️primary outcome - composite of death or hysterectomy < 42 days
➡️results were similar: 5.3% vs 5·5%; P=0.65
➡️death from bleeding was ⬇️ with TXA (1.5% vs 1.9%; P=0.045)
9/17
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- 🚩HALT-IT
➡️Published 2020
➡️12,009 pts with acute GI bleed
➡️164 hospitals in 15 countries
➡️primary outcome - death due to bleeding within 5 days
➡️results were similar: 4% vs 4% (RR 0·99, 95% CI 0·82–1·18)
➡️TXA caused ⬆️ venous thromboembolic events (0.8% vs 0.4%)
10/17
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- 🚩But, but, but...
➡️Following CRASH-2, TXA has been widely used and investigated in various haemorrhagic conditions
➡️Despite being a large international RCT, CRASH-2 raised many questions & divided opinion
11/17
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- 🚩Mechanism of Effect
➡️The mechanism of effect in CRASH-2 wasn't clear
➡️Rates of blood transfusion were similar
➡️Little data was available to explore other potential effects of TXA as the responsible mediator
12/17
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- 🚩Timing Issue
➡️There was an apparent differential response according to the timing of TXA administration
➡️< 1 hour - mortality 5.3% vs 7.7%
➡️1-3 hours - mortality 4.8% vs 6.1%
➡️> 3 hours - mortality 4.4% vs 3.1%
13/17
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- 🚩Generalisability
➡️98% of patients came from outside high income countries
➡️would TXA still be beneficial within a more comprehensive trauma system?
➡️would more advanced treatments dilute its effects?
➡️blood products / interventional radiology / REBOA 😉
14/17
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- 🚩Specificity
➡️The inclusion criteria have limited utility in recognising haemorrhage
➡️HR > 110/min & SBP < 90 mmHg
➡️neither do they identify acute traumatic coagulopathy (ATC) in pts who are more likely to benefit
➡️including non ATC patients may ⬆️ thromboses risk
15/17
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- 🚩PATCH Trial
➡️Enter the PATCH Trial
➡️Pre-hospital Anti-fibrinolytics for Traumatic Coagulopathy and Haemorrhage
➡️TXA (starting prehospital) vs placebo in 1316 patients with severe trauma at risk of ATC
➡️Australia / NZ / Germany
➡️Primary Outcome GOSE at 6 months
16/17
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- 🚩 Is TXA beneficial in more resourced healthcare systems?
Join us in @TitanicBelfast to hear @RussellGruen present the results of the @PATCHTrial
https://t.co/RD6WAgBYL3
@HawkmoonHEMS
17/17
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- @TitanicBelfast @RussellGruen @PATCHTrial @HawkmoonHEMS References
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