"Critically evaluate the use of tranexamic acid" is not a CICM Second Part SAQ at the time of writing (in April 2021), for reasons which may be entirely accidental. Certainly, trainees have been asked questions with much less clinical relevance. It has already appeared as a sub-section in several questions about trauma (Question 16 from the second paper of 2015) resuscitating the bleeding cardiothoracic catastrophe (Question 4 from the first paper of 2001) as well as in the First Part exam (Question 4 from the first paper of 2013). It is therefore only a matter of time before the unblinking alien gaze of the examiners falls upon it.
Without trespassing overmuch into primary exam territory, some sort of brief pharmacological rundown is probably called for here, as otherwise it would feel wrong to keep prescribing something when you don't have a clear idea of what it does. It's not exactly novel or exotic (we've had this stuff since 1962). In brief summary:
|Class||Serine protease inhibitor|
|Chemistry||Monocarboxylic acid (a synthetic derivative of the amino acid lysine)|
|Routes of administration||IV, nebulised, topical, oral|
|Absorption||50% absorbed from the GI tract; bioavailability is about 30-35%. Most of it is not metabolised.|
|Solubility||pKa of 10.22; highly water soluble, but minimally fat-soluble|
|Distribution||VOD = 0.18 L/kg; minimally protein bound (3%, all of which is accounted for by its binding to plasminogen). After some loading (eg. several doses over 24-36 hrs), enough of it distributes to the tissues to continue having a sustained antifibrinolytic effect for many hours.|
|Elimination||95% of the dose is excreted unchanged in the kidneys; half-life is 2 hours|
|Time course of action||Relatively short-acting, very rapid onset of effect|
|Mechanism of action||Competitive inhibitor of plasminogen activation (by binding to the 5-lysine site on plasminogen). This inhibts the formation of plasmin and displaces plasminogen from the surface of fibrin.|
|Clinical effects||Prevents the breakdown of fibrin, thus maintaing clot integrity. Numerous other effects (as it also inhibits other proteases), as well as indirect effects via plasminogen inhibition (eg. on complement activation, where by reducing plasmin activity it reduces the consumption of C1 esterase inhibitor)|
|Single best reference for further information||Data sheet from medsafe.govt.nz|
Aminocaproic acid (or epsilon-aminocaproic acid) was also available for many years, but was de-adopted because of hideous toxicity, including cardiac arrhythmias, rhabdomyolysis, and clots where one does not wish to have clots. Moreover, tranexamic acid has about 10 times the affinity for plasminogen.
One could classify the tranexamic acid trials into two broad categories, "trials that found something" and "trials that did not find any effect".
To summarise, the literature is divided as to whether this drug actually saves any lives or not, but there is broad agreement that it is safe in responsible doses, and even in irresponsibly large doses it apprears to have no effect on the risk of thromboembolism. As such, one would be well justified in writing something like "My practice is to continue using tranexamic acid in trauma patients, PPH and during/following cardiac surgery, as the risk appears low."
Pilbrant, Å., M. Schannong, and J. Vessman. "Pharmacokinetics and bioavailability of tranexamic acid." European journal of clinical pharmacology 20.1 (1981): 65-72.
Griffin, James D., and Leonard Ellman. "Epsilon-aminocaproic acid (EACA)." Seminars in thrombosis and hemostasis. Vol. 5. No. 1. 1978.
Wikkelsø, Anne Juul, et al. "Hyperfibrinolysis as the cause of haemorrhage and increased mortality in trauma patients." Ugeskrift for laeger 173.18 (2011): 1284-1287.
Theusinger, Oliver M., et al. "Hyperfibrinolysis diagnosed by rotational thromboelastometry (ROTEM®) is associated with higher mortality in patients with severe trauma." Anesthesia & Analgesia 113.5 (2011): 1003-1012.
Schöchl, H., et al. "Trauma-associated hyperfibrinolysis." Hämostaseologie 32.01 (2012): 22-27.
CRASH trial collaborators. "Effects of tranexamic acid on death, disability, vascular occlusive events and other morbidities in patients with acute traumatic brain injury (CRASH-3): a randomised, placebo-controlled trial." The Lancet 394.10210 (2019): 1713-1723.
Sprigg, Nikola, et al. "Tranexamic acid for hyperacute primary IntraCerebral Haemorrhage (TICH-2): an international randomised, placebo-controlled, phase 3 superiority trial." The Lancet 391.10135 (2018): 2107-2115.
Myles, Paul S., et al. "Tranexamic acid in patients undergoing coronary-artery surgery." New England Journal of Medicine 376.2 (2017): 136-148.