Tranexamic acid-associated seizures: Causes and treatment.
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ABSTRACT:
SUBMITTER: Lecker I
PROVIDER: S-EPMC4738442 | biostudies-other | 2016 Jan
REPOSITORIES: biostudies-other
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Project description:Antifibrinolytic drugs are widely used to reduce blood loss during surgery. One serious adverse effect of these drugs is convulsive seizures; however, the mechanisms underlying such seizures remain poorly understood. The antifibrinolytic drugs tranexamic acid (TXA) and ε-aminocaproic acid (EACA) are structurally similar to the inhibitory neurotransmitter glycine. Since reduced function of glycine receptors causes seizures, we hypothesized that TXA and EACA inhibit the activity of glycine receptors. Here we demonstrate that TXA and EACA are competitive antagonists of glycine receptors in mice. We also showed that the general anesthetic isoflurane, and to a lesser extent propofol, reverses TXA inhibition of glycine receptor-mediated current, suggesting that these drugs could potentially be used to treat TXA-induced seizures. Finally, we measured the concentration of TXA in the cerebrospinal fluid (CSF) of patients undergoing major cardiovascular surgery. Surprisingly, peak TXA concentration in the CSF occurred after termination of drug infusion and in one patient coincided with the onset of seizures. Collectively, these results show that concentrations of TXA equivalent to those measured in the CSF of patients inhibited glycine receptors. Furthermore, isoflurane or propofol may prevent or reverse TXA-induced seizures.
| S-EPMC3533541 | biostudies-literature
Project description:IntroductionSeizures are common after intracerebral haemorrhage. Tranexamic acid increases the risk of seizures in non-intracerebral haemorrhage population but its effect on post-intracerebral haemorrhage seizures is unknown. We explored the risk factors and outcomes of seizures after intracerebral haemorrhage and if tranexamic acid increased the risk of seizures in the Tranexamic acid for IntraCerebral Haemorrhage-2 trial.Patients and methodsSeizures were reported prospectively up to day 90. Cox regression analyses were used to determine the predictors of seizures within 90?days and early seizures (?7?days). We explored the effect of early seizures on day 90 outcomes.ResultsOf 2325 patients recruited, 193 (8.3%) had seizures including 163 (84.5%) early seizures and 30 (15.5%) late seizures (>7?days). Younger age (adjusted hazard ratio (aHR) 0.98 per year increase, 95% confidence interval (CI) 0.97–0.99; p?=?0.008), lobar haematoma (aHR 5.84, 95%CI 3.58–9.52; p?<?0.001), higher National Institute of Health Stroke Scale (aHR 1.03, 95%CI 1.01–1.06; p?=?0.014) and previous stroke (aHR 1.66, 95%CI 1.11–2.47; p?=?0.013) were associated with early seizures. Tranexamic acid did not increase the risk of seizure within 90?days. Early seizures were associated with worse modified Rankin Scale (adjusted odds ratio (aOR) 1.79, 95%CI 1.12–2.86, p?=?0.015) and increased risk of death (aOR 3.26, 95%CI 1.98–5.39; p?<?0.001) at day 90.Discussion and conclusion: Lobar haematoma was the strongest independent predictor of early seizures after intracerebral haemorrhage. Tranexamic acid did not increase the risk of post-intracerebral haemorrhage seizures in the first 90?days. Early seizures resulted in worse functional outcome and increased risk of death.
| S-EPMC7313371 | biostudies-literature
Project description:In cardiac surgery, use of the antifibrinolytic agent tranexamic acid (TXA) and acute perioperative stroke are both associated with convulsive seizures. We hypothesized that an older (preoperative) stroke increases the risk of TXA-associated seizures as well. To test this hypothesis, we retrospectively analyzed data from 16,110 patients who had undergone open-heart valvular surgery at our institution between 2009 and 2020. The dosing of TXA was moderate. Use of TXA and a history of stroke were both independently associated with convulsive seizure with an adjusted odds ratio (OR) of 2.40 (95%CI: 1.71-3.37) and 1.79 (95%CI: 1.27-2.54), respectively. Compared to patients without TXA administration, the adjusted OR of experiencing a seizure in TXA patients without a history of stroke was 2.44 (95%CI: 1.71-3.46) and in patients receiving TXA with a history of stroke 4.30 (95%CI: 2.65-6.99). However, there was no significant interaction between TXA use and preoperative stroke on convulsive seizures (P = 0.77). Compared to patients without seizure, for patients with seizure, the inverse probability-weighted ORs of in-hospital mortality and 30-day mortality were 3.58 (95%CI: 2.20-5.83) and 4.04 (95%CI: 2.34-6.98), respectively. We conclude that, in patients undergoing open-heart surgery, a history of stroke is independently associated with convulsive seizures but is not a contraindication for TXA use.
| S-EPMC8124038 | biostudies-literature
Project description:Seizures are the most frequent neurological clinical symptoms of the central nervous system (CNS) during the neonatal period. Neonatal seizures may be ascribed to an acute event or symptomatic conditions determined by genetic, metabolic or structural causes, outlining the so-called 'Neonatal Epilepsies'. To date, three main groups of neonatal epilepsies are recognised during the neonatal period: benign familial neonatal epilepsy (BFNE), early myoclonic encephalopathy (EME) and 'Ohtahara syndrome' (OS). Recent advances showed the role of several genes in the pathogenesis of these conditions, such as KCNQ2, KCNQ3, ARX, STXBP1, SLC25A22, CDKL5, KCNT1, SCN2A and SCN8A. Herein, we reviewed the current knowledge regarding the pathogenic variants most frequently associated with neonatal seizures, which should be considered when approaching newborns affected by these disorders. In addition, we considered the new possible therapeutic strategies reported in these conditions.
| S-EPMC8534058 | biostudies-literature
Project description:Uncontrolled massive bleeding with subsequent derangement of the coagulation system is a major challenge in the management of both surgical and seriously injured patients. Under physiological conditions activators and inhibitors of coagulation regulate the sensitive balance between clot formation and fibrinolysis. In some cases, excessive and diffuse bleeding is caused by systemic activation of fibrinolysis, i. e. hyperfibrinolysis (HF). Uncontrolled HF is associated with a high mortality. Polytrauma patients and those undergoing surgical procedures involving organs rich in plasminogen proactivators (e. g. liver, kidney, pancreas, uterus and prostate gland) are at a high risk for HF. Antifibrinolytics, such as tranexamic acid (TXA) are used for prophylaxis and treatment of bleeding caused by a local or generalized HF as well as other hemorrhagic conditions. TXA is a synthetic lysine analogue that has been available in Austria since 1966. TXA is of utmost importance in the prevention and treatment of traumatic and perioperative bleeding due to the resulting reduction in perioperative blood loss and blood transfusion requirements. The following article presents the different fields of application of TXA with particular respect to indications and dosages, based on a literature search and on current guidelines.
| S-EPMC5429347 | biostudies-literature
Project description:BackgroundTranexamic acid (TXA) reduces surgical bleeding and reduces death from bleeding after trauma and childbirth. However, its effects on thrombotic events and seizures are less clear. We conducted a systematic review and meta-analysis to examine the safety of TXA in bleeding patients.MethodsFor this systematic review and meta-analysis, we searched MEDLINE, EMBASE and the Cochrane Central Register of Controlled trials from inception until June 1, 2020. We included randomized trials comparing intravenous tranexamic acid and placebo or no intervention in bleeding patients. The primary outcomes were thrombotic events, venous thromboembolism, acute coronary syndrome, stroke and seizures. A meta-analysis was performed using a random effects model and meta-regression analysis was performed to evaluate how effects vary by dose. We assessed the certainty of evidence using the grading of recommendations, assessment, development and evaluations (GRADE) approach.ResultsA total of 234 studies with 102,681 patients were included in the meta-analysis. In bleeding patients, there was no evidence that TXA increased the risk of thrombotic events (RR = 1.00 [95% CI 0.93-1.08]), seizures (1.18 [0.91-1.53]), venous thromboembolism (1.04 [0.92-1.17]), acute coronary syndrome (0.88 [0.78-1.00]) or stroke (1.12 [0.98-1.27]). In a dose-by-dose sensitivity analysis, seizures were increased in patients receiving more than 2 g/day of TXA (3.05 [1.01-9.20]). Meta-regression showed an increased risk of seizures with increased dose of TXA (p = 0.011).ConclusionTranexamic acid did not appear to increase the risk of thrombotic events in bleeding patients. However, because there may be dose-dependent increase in the risk of seizures, very high doses should be avoided.
| S-EPMC8561958 | biostudies-literature
Project description:Birth asphyxia is often associated with a high seizure burden that is predictive of poor neurodevelopmental outcome. The mechanisms underlying birth asphyxia seizures are unknown. Using an animal model of birth asphyxia based on 6-day-old rat pups, we have recently shown that the seizure burden is linked to an increase in brain extracellular pH that consists of the recovery from the asphyxia-induced acidosis, and of a subsequent plateau level well above normal extracellular pH. In the present study, two-photon imaging of intracellular pH in neocortical neurons in vivo showed that pH changes also underwent a biphasic acid-alkaline response, resulting in an alkaline plateau level. The mean alkaline overshoot was strongly suppressed by a graded restoration of normocapnia after asphyxia. The parallel post-asphyxia increase in extra- and intracellular pH levels indicated a net loss of acid equivalents from brain tissue that was not attributable to a disruption of the blood-brain barrier, as demonstrated by a lack of increased sodium fluorescein extravasation into the brain, and by the electrophysiological characteristics of the blood-brain barrier. Indeed, electrode recordings of pH in the brain and trunk demonstrated a net efflux of acid equivalents from the brain across the blood-brain barrier, which was abolished by the Na/H exchange inhibitor, N-methyl-isobutyl amiloride. Pharmacological inhibition of Na/H exchange also suppressed the seizure activity associated with the brain-specific alkalosis. Our findings show that the post-asphyxia seizures are attributable to an enhanced Na/H exchange-dependent net extrusion of acid equivalents across the blood-brain barrier and to consequent brain alkalosis. These results suggest targeting of blood-brain barrier-mediated pH regulation as a novel approach in the prevention and therapy of neonatal seizures.
| S-EPMC3501974 | biostudies-literature
Project description:It is unclear how tranexamic acid (TXA) affects blood loss and seizures in meningioma resections. We performed a systematic review and meta-analysis and tried to evaluate the effectiveness and safety of TXA use for patients undergoing meningioma resections. Regards to this systematic review and meta-analysis (registered with CRD42023416693), we searched PubMed, Embase (Ovid), EBSCO, and Cochrane central library up to and including Oct 2023. Patients undergoing meningioma resections treated with TXA and placebo or no treatment were eligible for this study. This would allow delineation of the impact of TXA on blood loss, postoperative seizure, and other complication incidences. Four prospective cohort studies with 781 patients (390 patients in the TXA group and 391 patients in the control group) were conducted via a systematic review and meta-analysis. The results suggested that the application of TXA for patients undergoing meningioma resections reduced mean blood loss of 252 mL with 95% confidence interval (CI) -469.26 to -34.67 (P = 0.02) and I2 of 94% but did not increase postoperative seizure (risk ratio: 1.08; 95%CI: 0.54 to 2.15; P = 0.84) and other complication rates. This systematic review and meta-analysis suggests that the administration of TXA could reduce blood loss in patients undergoing intracerebral meningioma resection. The systematic review protocol has been registered at PROSPERO (Registration No. CRD42023416693) on April 23, 2023.
| S-EPMC11373793 | biostudies-literature
Project description:Stroke is a devastating and potentially preventable complication of cardiac surgery. Tranexamic acid (TXA) is a commonly antifibrinolytic agent in cardiac surgeries with cardiopulmonary bypass (CPB), however, there is concern that it might increase incidence of stroke after cardiac surgery. In this retrospective study, we investigated whether TXA usage could increase postoperative stroke in cardiac surgery.A retrospective study was conducted from January 1, 2010, to December 31, 2015, in 2,016 patients undergoing cardiac surgery, 664 patients received intravenous TXA infusion and 1,352 patients did not receive any antifibrinolytic agent. Univariate and propensity-weighted multivariate regression analysis were applied for data analysis.Intraoperative TXA administration was associated with postoperative stroke (1.7% vs. 0.5%; adjusted OR, 4.11; 95% CI, 1.33 to 12.71; p = 0.014) and coma (adjusted OR, 2.77; 95% CI, 1.06 to 7.26; p = 0.038) in cardiac surgery. As subtype analysis was performed, TXA administration was still associated with postoperative stroke (1.7% vs. 0.3%; adjusted OR, 5.78; 95% CI, 1.34 to 27.89; p = 0.018) in patients undergoing valve surgery or multi-valve surgery only, but was not associated with postoperative stroke (1.7% vs. 1.3%; adjusted OR, 5.21; 95% CI, 0.27 to 101.17; p = 0.276) in patients undergoing CABG surgery only. However, TXA administration was not associated with postoperative mortality (adjusted OR, 1.31; 95% CI, 0.56 to 3.71; p = 0.451), seizure (adjusted OR, 1.13; 95% CI, 0.42 to 3.04; p = 0.816), continuous renal replacement therapy (adjusted OR, 1.36; 95% CI, 0.56 to 3.28; p = 0.495) and resternotomy for postoperative bleeding (adjusted OR, 1.55; 95% CI, 0.55 to 4.30; p = 0.405). No difference was found in postoperative ventilation time (adjusted B, -1.45; SE, 2.33; p = 0.535), length of intensive care unit stay (adjusted B, -0.12; SE, 0.25; p = 0.633) and length of hospital stay (adjusted B, 0.48; SE, 0.58; p = 0.408).Based on the 5-year experience of TXA administration in cardiac surgery with CPB, we found that postoperative stroke was associated with intraoperative TXA administration in patients undergoing cardiac surgery, especially in those undergoing valve surgeries only. This study may suggest that TXA should be administrated according to clear indications after evaluating the bleeding risk in patients undergoing cardiac surgery, especially in those with high stroke risk.
| S-EPMC5446127 | biostudies-literature
Project description:BackgroundPostpartum hemorrhage (PPH) is responsible for nearly one quarter of maternal deaths. A 2017 multicountry trial found that incorporating tranexamic acid (TXA) into the PPH management package was effective in reducing maternal death due to bleeding.ObjectiveTo systematically review studies assessing the cost-effectiveness of tranexamic acid for PPH treatment.Search strategyNine databases were searched using variations of keywords 'tranexamic acid', 'postpartum hemorrhage' and 'cost effectiveness'.Selection criteriaEligible studies were any type of economic or effectiveness evaluation studies on tranexamic acid for treating women with PPH.Data collection and analysisTwo reviewers independently screened citations and extracted data on cost effectiveness measures. Quality was assessed using the Consensus on Health Economic Criteria list.Main resultsFour studies were included, of which two were abstracts. Three studies concluded that early administration of TXA was cost-saving or cost-effective. One abstract reported TXA was not cost-effective in the USA unless the probability of death due to hemorrhage is higher.ConclusionAvailable evidence (four studies in three countries) suggests that this life-saving intervention may be below willingness to pay thresholds (cost-effective) or cost saving. Further studies conducted in different populations and settings are needed to inform health policy decision-making to reduce PPH-associated morbidity and mortality.
| S-EPMC8596845 | biostudies-literature