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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2014  |  Volume : 25  |  Issue : 1  |  Page : 130-132
Tranexamic acid overdosage-induced generalized seizure in renal failure

1 Department of Nephrology, All India Institute of Medical Sciences, New Delhi, India
2 Department of Neurology, All India Institute of Medical Sciences, New Delhi, India

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Date of Web Publication7-Jan-2014


We report a 45-year-old lady with chronic kidney disease stage 4 due to chronic tubulointerstial disease. She was admitted to our center for severe anemia due to menorrhagia and deterioration of renal function. She was infused three units of packed cells during a session of hemodialysis. Tranexamic acid (TNA) 1 g 8-hourly was administered to her to control bleeding per vaginum. Two hours after the sixth dose of TNA, she had an episode of generalized tonic clonic convulsions. TNA was discontinued. Investigations of the patient revealed no biochemical or structural central nervous system abnormalities that could have provoked the convulsions. She did not require any further dialytic support. She had no further episodes of convulsion till dis­charge and during the two months of follow-up. Thus, the precipitating cause of convulsions was believed to be an overdose of TNA.

How to cite this article:
Bhat A, Bhowmik DM, Vibha D, Dogra M, Agarwal SK. Tranexamic acid overdosage-induced generalized seizure in renal failure. Saudi J Kidney Dis Transpl 2014;25:130-2

How to cite this URL:
Bhat A, Bhowmik DM, Vibha D, Dogra M, Agarwal SK. Tranexamic acid overdosage-induced generalized seizure in renal failure. Saudi J Kidney Dis Transpl [serial online] 2014 [cited 2022 Dec 4];25:130-2. Available from: https://www.sjkdt.org/text.asp?2014/25/1/130/124529

   Introduction Top

Tranexamic acid (TNA) is a synthetic lysine analogue that shows high affinity for the lysine-binding sites of plasminogen and plasmin. It shows strong antifibrinolytic activity in vitro and in vivo by preventing the interaction of plasminogen and plasmin with lysine residues on the surface of fibrin. It is seven to ten times more potent compared with the earliest anti-fibrinolytic agent - epsilon amino-caproic acid.

TNA is widely distributed throughout the intracellular and extracellular compartments and is excreted mainly unchanged in the urine. It can be administered orally or intravenously. [1] The recommended dose of TNA in patients with normal renal function is 500 mg three to four times a day. Because renal excretion is the major route of elimination of TNA, the dose in renal impairment has to be reduced progressively. In patients on dialysis, the dose of TNA should be as low as 250 mg in 24 h. TNA is frequently used in various disciplines like cardiology and neurosurgery and in obs­tetrics and gynecology wards as a hemostatic agent and "fibrin sealant." In animal studies, TNA has been shown to have an epileptogenic effect if applied topically to the cortex, [2] intrathecally [3] or even intravenously. [4] There are few reports of TNA-induced convulsions in humans. [5],[6] We report the case of an old lady with chronic kidney disease (CKD) who developed generalized convulsions following a TNA overdose.

   Case Report Top

A 45-year-old lady with CKD was admitted to our center for severe anemia due to menorrhagia. The patient was under follow-up of the renal clinic with the diagnosis of chronic tubulointerstitial disease (CTID), which was diag­nosed two years prior to admission. Her labo­ratory parameters three months ago on her last follow-up were as follows: hemoglobin 9.3 g/dL, serum urea 84 mg/dL, creatinine 4.1 mg/ dL and albumin 4 g/dL. She was on oral iron, folic acid, calcium carbonate, calcitriol and erythropoietin. On admission, she complained of active, intermittent bleeding per vaginum for the previous two months. There was no associated pain or bleeding from any other site. Workup was started to detect the cause of bleeding from local or systemic cause. Her hemoglobin at the time of admission was only 2.4 g/dL. Her urea and creatinine at the time of admission were 97 mg/dL and 4.7 mg/dL, res­pectively (creatinine clearance 16.9 mL/min). Her calcium and phosphorus were 9.8 mg/dL and 4.4 mg/dL, respectively. There was no evi­dence of sepsis. Three units of packed red blood cells and one session of hemodialysis were received by the patient within 12 h of admission. A gynecological consultation was obtained and TNA was started at a dose of 1 g intravenous 8 hourly. Two hours after the sixth dose of the drug, she had an episode of gene­ralized tonic-clonic convulsion. The episode lasted for 2 min and was controlled with intra­venous lorazepam 2 mg and administration of TNA was discontinued. The patient had no previous history of any seizure disorder. On repeat renal function testing, the urea and creatinine levels were 70 mg/dL and 3.71 mg/dL, respectively. Blood gas and serum analysis re­vealed mild compensated metabolic acidosis and normal serum calcium and serum sodium levels. The neurological examination was unremarkable. She subsequently underwent electro­encephalogram, NCCT head and magnetic resonance imaging of the brain, all of which were normal. She did not require any further dialytic support. She had no further episodes of convulsion till discharge and during two months of follow-up. The renal functions sta­bilized at her baseline serum creatinine level of 4.0 mg/dL.

   Discussion Top

The patient received parenteral TNA without appropriate dose modifications for renal im­pairment. TNA is generally well tolerated. Side-effects are mainly gastrointestinal, such as nausea, vomiting, diarrhea and abdominal pain. Inadvertent intrathecal administration of TNA has been shown to cause convulsions. , [7] Overdosage with TNA (500 mg QID) in a pa­tient with continuous ambulatory peritoneal dialysis has been reported to cause multifocal myoclonus. [8] One patient on hemodialysis had visual disturbance following TNA overdosage. [9] In one study, routine use of TNA (4 g) during cardiac surgery was associated with higher incidence of seizures as compared with aprotinin. There was no difference in the occur­rence of renal failure in the two groups. [6] In another recent study, administration of high doses (61-259 mg/kg) of TNA in cardiac sur­gery patients was associated with seizures, which did not result in any permanent neu­rological abnormality. [10] TNA binds to the y -aminobutyric acid (GAB A) binding site of GABA A receptors in membranes from rat cere­bral cortex and may induce hyperexcitability by blocking GABA-driven inhibition of the central nervous system. [11] Other drugs that may induce seizures by modulating neurotransmis­sion include application of excitatory transmit­ters such as kainic acid and inhibitory receptor blockers such as penicillin. [4] TNA is eliminated by glomerular filtration, excretion being about 30% at 1 h, 55% at 3 h and 90% at 24 h after IV administration of 10 mg/kg. After oral ad­ministration of 10-15 mg/kg, excretion is 1% at 1 h, 7% at 3 h and 39% at 24 h. [1] Thus, in a patient with CKD, an overdose is likely to occur if appropriate dose reduction is not per­formed. The following dose adjustments have been suggested: glomerular filtration rate (GFR) >50 mL/min 50% of dose, GFR 10-50 mL/ min 25% of dose, GFR <10 mL/min/HD/PD 10% of the dose and for patients on CRRT 25% of the dose. [12] Our patient had CKD and inadvertently received high doses of TNA. She was dialyzed to facilitate blood transfusion and also to correct uremic coagulopathy. Investi­gations of the patient following the seizure revealed no biochemical or structural central nervous system abnormality that could have provoked the convulsion. Dialysis disequili­brium is an unlikely cause of the seizure, as the duration of the first dialysis was short and the seizure occurred 24 h after dialysis with no neurological problem in the interim period. Also, there were no episodes of accelerated hypertension; hence, hypertensive encephalopathy as a cause of seizure is not likely. Thus, the precipitating cause of seizure was thought to be due to TNA. The cessation of seizure after the withdrawal of TNA and the absence of requirement for maintenance anti-epileptic therapy also hint at a very possible relation­ship.

TNA should be given in appropriately modi­fied doses in patients with renal impairment. The cause and effect relationship of drug-induced seizures may be overlooked in this subset of patients due to the associated mul­tiple metabolic problems like uremia, dyselectrolemia and renal failure-induced coagulopathic intracerebral bleed. It may therefore be underreported in the literature. The FDA label information regarding TNA only mentions myoclonus as one of the possible adverse effects in case of overdose of TNA; genera­lized convulsion is not mentioned. However, it is important for health care providers to be aware of this condition.

   References Top

1.Nilsson IM. Clinical pharmacology of amino-caproic and tranexamic acids. J Clin Pathol Suppl (R Coll Pathol) 1980;14:41-47.  Back to cited text no. 1
2.Pellegrini A, Giaretta D, Chemello R, Zanotto L, Testa G. Feline generalized epilepsy in­duced by tranexamic acid (AMCA). Epilepsia 1982;23:35-45.  Back to cited text no. 2
3.de Leede-van der Maarl MG, Hilkens P, Bosch F. The epileptogenic effect of tranexamic acid. J Neurol 1999;246:843.  Back to cited text no. 3
4.Yamaura A, Nakamura T, Makino H, Hagihara Y. Cerebral complication of antifibrinolytic the­rapy in the treatment of ruptured intracranial aneurysm. Animal experiment and a review of literature. Eur Neurol 1980;19:77-84.  Back to cited text no. 4
5.Yeh H, Lau H, Lin P, Sun W, Mok MS. Con­vulsions and refractory ventricular fibrillation after intrathecal injection of a massive dose of tranexamic acid. Anesthesiology 2003;98:270-2.  Back to cited text no. 5
6.Martin K, Wiesner G, Breuer T, Lange R, Tassani P. The risks of aprotinin and tranexamic acid in cardiac surgery: A one-year follow-up of 1188 consecutive patients. Anesth Analg 2008;107:1783-90.  Back to cited text no. 6
7.Mohseni K, Jafari A, Nobahar MR, Arami A. Polymyoclonus seizure resulting from acci­dental injection of tranexamic acid in spinal anesthesia. Anesth Analg 2009;108:1984-6.  Back to cited text no. 7
8.Hui AC, Wong TY, Chow KM, Szeto CC. Multifocal myoclonus secondary to tranexamic acid. J Neurol Neurosurg Psychiatry 2003;74: 547.  Back to cited text no. 8
9.Kitamura H, Matsui I, Itoh N, et al. Tranexamic acid-induced visual impairment in a hemodialysis patient. Clin Exp Nephrol 2003; 7:311-4.  Back to cited text no. 9
10.Murkin JM, Falter F, Granton J, Young B, Burt C, Chu M. High-dose tranexamic Acid is associated with nonischemic clinical seizures in cardiac surgical patients. Anesth Analg 2010;110:350-3.  Back to cited text no. 10
11.Furtmüller R, Schlag MG, Berger M, et al. Tranexamic acid, a widely used antifibrinolytic agent, causes convulsions by a gamma-aminobutyric acid(A) receptor antagonistic effect. J Pharmacol Exp Ther 2002;301:168-73.  Back to cited text no. 11
12.McIntyre CW, Owen PJ. Prescribing drugs in kidney disease. In: Brenner BM, edr. Brenner & Rector's The Kidney. Philadelphia: Saunders, an imprint of Elsevier Inc.; 2008. p. 1930-53.  Back to cited text no. 12

Correspondence Address:
Dipankar M Bhowmik
Department of Nephrology, All India Institute of Medical Sciences, New Delhi - 110 029
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1319-2442.124529

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