Special considerations with regard to the dosage of tranexamic acid in patients with chronic renal diseases

Andersson, Lennart; Eriksson, Olle; Hedlund, Per Olov; Kjellman, H; Lindqvist, Bengt

doi:10.1007/bf00255578

Cited by 56 publications

(35 citation statements)

References 10 publications

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“…Furthermore, all patients except one achieved and maintained intraoperative tranexamic acid concentrations of greater than 100 lg.ml , a level that correlates to $80% inhibition of tissue plasminogen activator [18]. Three patients demonstrated plasma tranexamic acid concentrations greater than 10 lg.ml )1 up to 8 h postoperatively.…”

Section: Resultsmentioning

confidence: 81%

“…, a range deemed adequate to achieve 100% inhibition of tissue plasminogen activator and hence ensure effective inhibition of systemic fibrinolysis [18]. Furthermore, all patients except one achieved and maintained intraoperative tranexamic acid concentrations of greater than 100 lg.ml , a level that correlates to $80% inhibition of tissue plasminogen activator [18].…”

Section: Resultsmentioning

confidence: 90%

“…The main objective of this study was to measure the tranexamic acid plasma concentrations following infusion of the BART dosing regimen before, during, and after cardiac surgery with the use of CPB. The secondary objectives of this study were to ascertain if peri-operative tranexamic acid concentrations were within the suggested target range to allow optimal inhibition of tissue plasminogen activator and to evaluate the elimination kinetics of tranexamic acid in the postoperative period following discontinuation of the infusion [18]. We hypothesised that as tranexamic acid is virtually devoid of plasma protein binding and filtered by the glomeruli, the clearance and distribution of tranexamic acid would remain unchanged during the peri-operative period following administration of the BART dose in patients with normal kidney function.…”

Section: Discussionmentioning

confidence: 99%

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Pharmacokinetics of tranexamic acid in patients undergoing cardiac surgery with use of cardiopulmonary bypass*

et al. 2012

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SummaryWe conducted a study to assess pharmacokinetics of high-dose tranexamic acid for 24 h after administration of the drug in patients undergoing cardiac surgery with cardiopulmonary bypass. High-dose tranexamic acid involved a bolus of 30 mg.kg )1 infused over 15 min followed by a 16 mg.kg.h )1 infusion until chest closure with a 2 mg.kg )1 load within the pump prime. Tranexamic acid followed first-order kinetics best described using a two-compartment model, with a total body clearance that approximated the glomerular filtration rate. Mean plasma tranexamic acid concentrations during the intra-operative period and in the first 6 postoperative hours were consistently higher than the suggested threshold to achieve 100% inhibition and 80% inhibition of tissue plasminogen activator. With recent studies implicating high-dose tranexamic acid as a possible aetiology of postoperative seizures following cardiac surgery, the minimum effective yet safe dose of tranexamic acid in high-risk cardiac surgery needs to be refined. Tranexamic acid, a synthetic antifibrinolytic, is a lysine derivative that competitively inhibits the activation of plasminogen, thereby reducing the conversion of plasminogen to plasmin, an enzyme that degrades fibrin clots, fibrinogen, and other plasma proteins, including the procoagulant factors V and VIII [1]. At higher doses, tranexamic acid directly inhibits plasmin activity [2][3][4][5]. Tranexamic acid thus inhibits fibrinolysis, a putative mechanism of bleeding after cardiopulmonary bypass (CPB) [6]. Hence, this compound is routinely used during cardiac surgery procedures involving CPB, to reduce blood loss [1][2][3][4][5]. Tranexamic acid is considered to have a good safety profile. However, this has been challenged recently as several studies have found an association between high-dose tranexamic acid administration and an increased incidence in postoperative

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Section: Resultsmentioning

confidence: 81%

Section: Resultsmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

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Pharmacokinetics of tranexamic acid in patients undergoing cardiac surgery with use of cardiopulmonary bypass*

et al. 2012

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“…Intravenous TXA is eliminated entirely through the kidneys and could accumulate in patients with chronic renal failure (CRF) [15]. Adverse effects of TXA treatment have been reported in kidney diseases [27-29].…”

Section: Discussionmentioning

confidence: 99%

“…Upon hospital admission, patients in the TXA group were given intravenous drip of TXA and at the same time also given snake venom blood coagulation enzyme by intramuscular injection (1000 U) once followed by intravenous injection (1000 U) once daily until the disappearance of macroscopic hematuria for 48h. The dosage of TXA was adjusted according to serum creatinine levels in patients with impaired renal function: for patients with serum creatinine levels <250 µmol/L, 10 mg/kg intravenously (IV) injection twice daily; for patients with serum creatinine concentrations of 250 to 500 µmol/L, 10 mg/kg IV injection once daily; for patients with serum creatinine levels >500 µmol/L, 5mg/kg IV injection once daily [15]. Thus most patients in the TXA group were administrated with TXA at the dose of 0.5 g via IV injection once or twice daily.…”

Section: Study Population and Methodsmentioning

confidence: 99%

Treatment of Persistent Gross Hematuria with Tranexamic Acid in Autosomal Dominant Polycystic Kidney Disease

Yao

Zhou

et al. 2017

Kidney Blood Press Res

585

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Background/Aims: In this retrospective study we aimed to compare the effect of tranexamic acid (TXA) vs etamsylate, two hemostatic agents, on hematuria duration in autosomal dominant polycystic kidney disease (ADPKD) patients with persistent gross hematuria. Methods: This is a retrospective study of 40 patients with ADPKD and macroscopic hematuria. 20 patients receiving TXA and snake venom blood clotting enzyme injection were compared with 20 matched patients receiving etamsylate and snake venom blood clotting enzyme injection. The primary outcome was hematuria duration and the secondary outcomes were blood transfusion requirements and adverse events. Results: The hematuria duration was shorter in the TXA group compared with the etamsylate group (4[3-5] d vs 7[6-10] d, P<0.001). The volume of blood transfusion tended to be less in the TXA group than in the etamsylate group (300±115 ml vs 486±195 ml, P=0.12), and the number of patients needing a blood transfusion also tended to be lower [20% (4/20) vs 35% (7/20), P=0.29]. TXA and etamsylate were equally well tolerated and no serious adverse events were observed in both groups. Conclusions: Our study indicates that TXA treatment was more effective than etamsylate in stopping bleeding in ADPKD patients with persistent gross hematuria.

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Pharmacokinetic modeling of tranexamic acid for patients undergoing cardiac surgery with normal renal function and model simulations for patients with renal impairment

Yang

Jerath

Bies

et al. 2015

Biopharm & Drug Disp

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Tranexamic acid (TXA), an effective anti‐fibrinolytic agent that is cleared by glomerular filtration, is used widely for cardiopulmonary bypass (CPB) surgery. However, an effective dosing regimen has not been fully developed in patients with renal impairment. The aims of this study were to characterize the inter‐patient variability associated with pharmacokinetic parameters and to recommend a new dosing adjustment based on the BART dosing regimen for CPB patients with chronic renal dysfunction (CRD). Recently published data on CPB patients with normal renal function (n = 15) were re‐examined with a two‐compartment model using the ADAPT5® and NONMEMVII® to identify covariates that explain inter‐patient variability and to ascertain whether sampling strategies might affect parameter estimation. A series of simulations was performed to adjust the BART dosing regimen for CPB patients with renal impairment. Based on the two‐compartmental model, the number of samples obtained after discontinuation of TXA infusion was found not to be critical in parameter estimation (p > 0.05). Both body weight and creatinine clearance were identified as significant covariates (p < 0.005). Simulations showed significantly higher than normal TXA concentrations in CRD patients who received the standard dosing regimen in the BART trial. Adjustment of the maintenance infusion rate based on the percent reduction in renal clearance resulted in predicted plasma TXA concentrations that were safe and therapeutic (~100 mg·L−1). Our proposed dosing regimen, with consideration of renal function, is predicted to maintain effective target plasma concentrations below those associated with toxicity for patients with renal failure for CPB. Copyright © 2015 John Wiley & Sons, Ltd.

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Special considerations with regard to the dosage of tranexamic acid in patients with chronic renal diseases

Cited by 56 publications

References 10 publications

Pharmacokinetics of tranexamic acid in patients undergoing cardiac surgery with use of cardiopulmonary bypass*

Pharmacokinetics of tranexamic acid in patients undergoing cardiac surgery with use of cardiopulmonary bypass*

Treatment of Persistent Gross Hematuria with Tranexamic Acid in Autosomal Dominant Polycystic Kidney Disease

Pharmacokinetic modeling of tranexamic acid for patients undergoing cardiac surgery with normal renal function and model simulations for patients with renal impairment

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