Tranexamic acid–associated seizures: Causes and treatment

Abstract

Antifibrinolytic drugs are routinely used worldwide to reduce the bleeding that results from a wide range of hemorrhagic conditions. The most commonly used antifibrinolytic drug, tranexamic acid, is associated with an increased incidence of postoperative seizures. The reported increase in the frequency of seizures is alarming, as these events are associated with adverse neurological outcomes, longer hospital stays, and increased in‐hospital mortality. However, many clinicians are unaware that tranexamic acid causes seizures. The goal of this review is to summarize the incidence, risk factors, and clinical features of these seizures. This review also highlights several clinical and preclinical studies that offer mechanistic insights into the potential causes of and treatments for tranexamic acid–associated seizures. This review will aid the medical community by increasing awareness about tranexamic acid–associated seizures and by translating scientific findings into therapeutic interventions for patients. ANN NEUROL 2016;79:18–26

Trauma‐targeted delivery of tranexamic acid improves hemostasis and survival in rat liver hemorrhage model

“…Furthermore, the optimal dosing of intravenous TXA remains an open question. Emerging studies have also implicated TXA in systemic coagulopathies, thromboembolism, and neuropathy, possibly also stemming from off‐target effects of TXA. These observations emphasize further optimization of TXA‐based antifibrinolytic strategies for safe and effective hemorrhage control.…”

“…Recent and ongoing clinical trials indicate a beneficial role of TXA in mitigating traumatic hemorrhage before and while in the hospital . At the same time, several emerging reports emphasize potential systemic risks of TXA, especially at high or repeat dose, in the context of off‐target thrombosis, thromboembolism, and neuropathy . Such findings have prompted recent research into packaging of TXA within various delivery vehicles to explore site‐localized release however, these reports are primarily focused on topical application of TXA‐loaded particles directly at the injury site.…”

The effect of different dose regimens of tranexamic acid in reducing blood loss during hip surgery

“…[123] Recent literature has revealed that TA causes seizures by inhibition of gamma-aminobutyric acid receptors and alterations in cerebral blood flow and this risk is dose dependent. [18] With the possibility of seizures at higher doses and inadequate antifibrinolysis at low doses, administration of optimal dose of TA at optimal rate becomes important.…”

The expanding role of tranexamic acid in the management of obstetric hemorrhage

“…Tranexamic acid is a competitive antagonist of gamma-aminobutyric acid (GABA), which reduces the inhibition of neurotransmission thus increases excitability in neural networks. Dose dependent seizure activity has been reported with an incidence of 0.9-2.5% in non-obstetric patients, but this effect has generally not been observed with to the same degree in pregnant patients for unclear reasons (19).…”