High-Dose Tranexamic Acid Is an Independent Predictor of Early Seizure After Cardiopulmonary Bypass

Kalavrouziotis, Dimitri; Voisine, Pierre; Mohammadi, Siamak; Dionne, Stéphanie; Dagenais, François

doi:10.1016/j.athoracsur.2011.07.085

Cited by 144 publications

(137 citation statements)

References 31 publications

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“…Other important risk factors for TXA‐associated seizures include the type and duration of surgery. Most seizures are reported in patients undergoing “open chamber surgery” (eg, aortic valve replacement) 16, 17, 18, 20. The risk is also increased in patients with deep hypothermic circulatory arrest, long cardiopulmonary bypass time, or prolonged aortic cross‐clamp time 16, 18, 20, 26…”

Section: Clinical Indications Incidence and Risk Factorsmentioning

confidence: 99%

“…However, observational clinical trials and case reports have shown that TXA, and to a lesser extent EACA, but not aprotinin, are associated with seizures 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34. Most TXA‐associated seizures occur in patients who have undergone cardiac procedures 16, 17, 18, 20, 21, 24, 25, 26, 30, 31, 32, 34. However, several case reports indicate that TXA‐associated seizures also occur in nonsurgical patients 10, 22, 27.…”

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confidence: 99%

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Tranexamic acid–associated seizures: Causes and treatment

Lecker

Wang

Whissell

et al. 2015

Annals of Neurology

219

158

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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

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Section: Clinical Indications Incidence and Risk Factorsmentioning

confidence: 99%

mentioning

confidence: 99%

Tranexamic acid–associated seizures: Causes and treatment

Lecker

Wang

Whissell

et al. 2015

Annals of Neurology

219

158

View full text Add to dashboard Cite

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“…15 There are five kringle domains in plasmin-(ogen), and each has an LBS. The amino acid sequence identity between the kringle domains are around 70%.…”

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confidence: 99%

Discovery of the Fibrinolysis Inhibitor AZD6564, Acting via Interference of a Protein–Protein Interaction

Cheng

Pettersen

Ohlsson

et al. 2014

ACS Med. Chem. Lett.

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A class of novel oral fibrinolysis inhibitors has been discovered, which are lysine mimetics containing an isoxazolone as a carboxylic acid isostere. As evidenced by X-ray crystallography the inhibitors bind to the lysine binding site in plasmin thus preventing plasmin from binding to fibrin, hence blocking the protein−protein interaction. Optimization of the series, focusing on potency in human buffer and plasma clotlysis assays, permeability, and GABAa selectivity, led to the discovery of AZD6564 (19) displaying an in vitro human plasma clot lysis IC 50 of 0.44 μM, no detectable activity against GABAa, and with DMPK properties leading to a predicted dose of 340 mg twice a day oral dosing in humans.

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“…37,38 The incidence of postoperative seizures in cardiac surgical patients receiving high TXA doses has been reported to be as high as 7.3% compared to 1.0% in placebo group. 39 In contrast, in a large cohort of around 1600 children having craniofacial surgery there was no significant difference in the incidence of seizures. 40 As a result of inhibiting fibrinolysis, though there is a theoretical possibility of an increased risk of thromboembolic events, it is biologically unlikely when used in situations where there is a shift from physiological fibrinolysis to hyperfibrinolysis (as seen during major surgery and trauma).…”

mentioning

confidence: 90%

Effect of prophylactic tranexamic acid on blood conservation in Indian women undergoing abdominal hysterectomy

Arthi

Jalakandan

Gunaseelan

2018

Int J Reprod Contracept Obstet Gynecol

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Background: The prevalence of anemia in India is so high that majority of women presenting for hysterectomy are already with borderline hemoglobin status and the perioperative blood loss puts them at risk of death and prolongs recovery. Antifibrinolytic agents, mainly Tranexamic acid (TXA) have been demonstrated to reduce blood loss and transfusion requirements in various surgeries. The present study was done to assess the efficacy of TXA in effectively reducing intraoperative blood loss and the need for transfusion in Indian population undergoing abdominal hysterectomy for benign indications.Methods: This randomized, double-blind, placebo-controlled study was conducted on hundred patients undergoing abdominal hysterectomy. Group T (n = 50)- received TXA 15 mg/kg in 100 ml Normal saline and Group N (n = 50)-received the same volume of Normal saline infused over 15 minutes. Estimated blood loss need for blood transfusion, duration of surgery, postoperative hemoglobin and incidence of adverse events were noted.Results: There was statistically significant reduction in mean blood loss in group T when compared to group N (360 ml versus 540 ml). Accordingly, there was significant difference in the number of patients requiring blood transfusion (12% versus 42%) and also the postoperative hemoglobin levels. The group T patients had a significantly shorter operating time (127.86 versus 148.64 minutes). None of the patients developed any major adverse events.Conclusions: The prophylactic TXA safely and effectively reduces the blood loss and transfusion requirements in Indian patients undergoing abdominal hysterectomy for benign indications.

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High-Dose Tranexamic Acid Is an Independent Predictor of Early Seizure After Cardiopulmonary Bypass

Cited by 144 publications

References 31 publications

Tranexamic acid–associated seizures: Causes and treatment

Tranexamic acid–associated seizures: Causes and treatment

Discovery of the Fibrinolysis Inhibitor AZD6564, Acting via Interference of a Protein–Protein Interaction

Effect of prophylactic tranexamic acid on blood conservation in Indian women undergoing abdominal hysterectomy

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