Tranexamic Acid (TXA) (Cyklokapron)

Anesthesia Implications

Classification: Antifibrinolytic
Therapeutic Effects: Reduced blood loss

Contraindications

Absolute – DVT or PE within 12 months of injury, history of DVT or PE anticoagulation treatment, known congenital thrombophilia, cardiac stent within one year, ischemic stroke within one year.

Relative – renal impairment, severe ischemic heart disease, history of thromboembolic or vascular disease, disseminated intravascular coagulation (DIC), history of seizures.

Primary Considerations

Seizures – GABA-A and glycine receptors mediate inhibition of the CNS. TXA appears to potentially interfere or inhibit these receptors, which is the predicted reason for increased excitability/proconvulsant symptoms seen after administration. The severity of symptoms appears to be directly related to dosing amount. Propofol and isoflurane are considered first-line prevention and treatment for TXA-associated seizures. These seizures occur most frequently during the early postoperative period after cardiac surgery, but can occur in noncardiac surgical and medical treatments as well. To reduce the risk of this happening, the lowest effective dose should be administered and adjustment should be made for morbidities such as renal dysfunction. Focal seizures, myoclonus, or twitching should cue discontinuance of TXA administration and initiation of EEG monitoring.

Dosing – It is undetermined which dosing is optimal. One major study indicated that lower doses (less than 50 mg/kg) are just as effective as high doses, but vastly reduce the likelihood of a TXA-induced seizure.

Timing – more studies need to be done to determine the ideal timing for TXA administration. As such, the administration time of TXA is VERY surgeon specific, so make sure to ask!

Routine use – studies validate that there may be reason for concern if the use of TXA is a ROUTINE measure to reduce blood loss in patients without known coagulopathies. While there doesn’t appear to be an increase in morbidity from thromboembolic events, there needs to be more trials conducted to determine appropriate dosing regimens for different surgical populations.

Pediatric patients – the safety of antifibrinolytics like TXA requires more studies in pediatric populations.

Reduced Transfusions – TXA use is associated with reduced blood transfusions WITHOUT increased thromboembolic events. These benefits are seen in orthopedic, neuro, obstetric, liver, and cardiac surgery.

Trauma – studies show that the early administration of TXA resulted in significantly reduced all-cause mortality. This included death due to bleeding, but also included death due to other causes. In the studies, there was no significant increase in thromboembolic events for PE, DVT, stroke, MI, multi-organ failure, or head injury. Conclusions of these studies suggest that TXA SAFELY reduces the risk of death from bleeding in hemorrhaging trauma patients if given within one hour of injury. However, greater than 3 hours from the time of injury may predispose the patient to being acidotic, hypothermic, and in a prothrombotic phase. As such, TXA may worsen the patient’s condition if given more than 3 hours after the injury.

IV push dose

Optimal doses are undetermined.

Most common: 1 gram at the surgeons preferred time.

Method of Action

Normally, fibrinogen is converted to fibrin, which binds with platelets and forms a hemostatic clot where there’s a vascular injury. That clot is enzymatically broken down after hemostasis is achieved. Simplistically, plasmin is the primary culprit for breaking down the clot (though there are several steps to the process). As fibrin is broken down, lysine binding sites are exposed, which enhances plasmin formation until the clot is dissolved. Tranexamic acid is a lysine analogue, which means it can bind to those lysine sites and block widespread plasmin activation (substantially slowing the breakdown of fibrin/clotting).

Simmons. Tranexamic Acid: From Trauma to Routine Perioperative Use. 2015. web link
Ortmann. Antifibrinolytic agents in current anaesthetic practice. British journal of anaesthesia. 2013.
Neurol. Tranexamic acid–associated seizures: Causes and treatment. 2016. web link
Rahmani. Tranexamic acid dosing strategies and blood loss reduction in multilevel spine surgery: A systematic review and network meta-analysis. 2021. web link