Prevention of postbypass bleeding with tranexamic acid and ϵ-aminocaproic acid

Karski, Jacek; Teasdale, S. J.; Norman, Peter H.; Carroll, Jo; Weisel, Richard D.; Glynn, Michael

doi:10.1016/1053-0770(93)90165-h

Cited by 92 publications

(25 citation statements)

References 22 publications

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“…The high dose of 4 g + 6 g (60 mg/kg as a loading dose followed by a 16 mg/kg/hour infusion) TA was chosen in our study as the best clinically effective dose used to reduce haemorrhage in high-risk cardiac surgery patients [17,18,20,21]. At the beginning of the study, these were the only data available on active doses in reducing haemorrhage.…”

Section: Discussionmentioning

confidence: 99%

“…After the loading dose infusion, a maintenance infusion of 1 g/hour was initiated and maintained for 6 hours. This high dose was chosen as the best dose for the reduction of bleeding in high-risk cardiac surgery [17,18] and was administered to reduce significant active haemorrhage of more than 800 mL the clinical course of which might be life-threatening.…”

Section: Methodsmentioning

confidence: 99%

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High-dose tranexamic acid reduces blood loss in postpartum haemorrhage

et al. 2011

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IntroductionOur purpose in conducting this study was to determine whether administration of high-dose tranexamic acid (TA) at the time of diagnosis of postpartum haemorrhage (PPH) could reduce blood loss.MethodsThis was a randomised, controlled, multicentred, open-label trial. Women with PPH >800 mL following vaginal delivery were randomly assigned to receive TA (loading dose 4 g over 1 hour, then infusion of 1 g/hour over 6 hours) or not. In both groups, packed red blood cells (PRBCs) and colloids could be used according to French guidelines. The use of additional procoagulant treatments was permitted only in cases involving intractable bleeding. The primary objective was to assess the efficacy of TA in the reduction of blood loss in women with PPH, and the secondary objectives were the effect of TA on PPH duration, anaemia, transfusion and the need for invasive procedures.ResultsA total of 144 women fully completed the protocol (72 in each group). Blood loss between enrolment and 6 hours later was significantly lower in the TA group than in the control group (median, 173 mL; first to third quartiles, 59 to 377) than in controls (221 mL; first to third quartiles 105 to 564) (P = 0.041). In the TA group, bleeding duration was shorter and progression to severe PPH and PRBC transfusion was less frequent than in controls (P < 0.03). Invasive procedures were performed in four women in the TA group and in seven controls (P = NS). PPH stopped after only uterotonics and PRBC transfusion in 93% of women in the TA group versus 79% of controls (P = 0.016). Mild, transient adverse manifestations occurred more often in the TA group than in the control group (P = 0.03).ConclusionsThis study is the first to demonstrate that high-dose TA can reduce blood loss and maternal morbidity in women with PPH. Although the study was not adequately powered to address safety issues, the observed side effects were mild and transient. A larger international study is needed to investigate whether TA can decrease the need for invasive procedures and reduce maternal morbidity in women with PPH.Trial registrationControlled Trials ISRCTN09968140.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

High-dose tranexamic acid reduces blood loss in postpartum haemorrhage

et al. 2011

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“…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.…”

Section: Discussionmentioning

confidence: 99%

“…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].…”

mentioning

confidence: 99%

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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“…TA has been reported to be effective in cardiac surgery [10,11], and is not likely to affect platelet function or other hemostatic parameters in patients with subarachnoid hemorrhage [12]. The former cases seem to involve a high fibrinolytic state.…”

Section: Discussionmentioning

confidence: 97%

Prophylactic hemostatic drugs do not reduce hemorrhage: Thromboelastographic study during upper abdominal surgery

et al. 1995

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Although a number of hemostatic drugs are currently used during surgery to reduce hemorrhage, their effects on bleeding are still controversial. Furthermore, few studies have been made on their prophylactic effects. The purpose of this study was to clarify the effects of hemostatic drugs on bleeding. Thirty adult patients undergoing upper abdominal surgery were randomly assigned to receive carbazochrome sodium sulfonate and tranexamic acid immediately after induction of anesthesia (group H,n=15) or no hemostatic drugs (group C,n=15). Common coagulation-tests [prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB)], thromboelastography [reaction time (R), coagulation time (K), maximum amplitude (MA), clot formation rate (α)], and determination of bleeding time were conducted before induction of anesthesia and just before the completion of surgery. PT, R, and K decreased significantly in both groups, while MA and α increased and FIB decreased significantly in group C. No significant difference in blood loss was observed between the groups. Our findings, therefore, suggest that these two hemostatic drugs do not have prophylactic effects on intraoperative bleeding. Further studies are, however, necessary before applying these results to all surgical patients.

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Prevention of postbypass bleeding with tranexamic acid and ϵ-aminocaproic acid

Cited by 92 publications

References 22 publications

High-dose tranexamic acid reduces blood loss in postpartum haemorrhage

High-dose tranexamic acid reduces blood loss in postpartum haemorrhage

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

Prophylactic hemostatic drugs do not reduce hemorrhage: Thromboelastographic study during upper abdominal surgery

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