The Dose-Response Relationship of Tranexamic Acid

Horrow, Jan C.; Riper, Daniel F. Van; Strong, Michael D.; Grunewald, Karl; Parmet, Jonathan L.

doi:10.1097/00000542-199502000-00009

Cited by 273 publications

(94 citation statements)

References 40 publications

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“…Previous studies have shown no significant difference in mortality benefit between low and high doses of TXA 29,30. In emergency situations, a fixed one-gram dose followed by a one-gram maintenance dose (if a patient continued to satisfy inclusion criteria), has been deemed most practical 12.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Tranexamic Acid in Prehospital Traumatic Hemorrhagic Shock: Outcomes of the Cal-PAT Study

Dong

et al. 2017

WestJEM

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IntroductionThe California Prehospital Antifibrinolytic Therapy (Cal-PAT) study seeks to assess the safety and impact on patient mortality of tranexamic acid (TXA) administration in cases of trauma-induced hemorrhagic shock. The current study further aimed to assess the feasibility of prehospital TXA administration by paramedics within the framework of North American emergency medicine standards and protocols.MethodsThis is an ongoing multi-centered, prospective, observational cohort study with a retrospective chart-review comparison. Trauma patients identified in the prehospital setting with signs of hemorrhagic shock by first responders were administered one gram of TXA followed by an optional second one-gram dose upon arrival to the hospital, if the patient still met inclusion criteria. Patients administered TXA make up the prehospital intervention group. Control group patients met the same inclusion criteria as TXA candidates and were matched with the prehospital intervention patients based on mechanism of injury, injury severity score, and age. The primary outcomes were mortality, measured at 24 hours, 48 hours, and 28 days. Secondary outcomes measured included the total blood products transfused and any known adverse events associated with TXA administration.ResultsWe included 128 patients in the prehospital intervention group and 125 in the control group. Although not statistically significant, the prehospital intervention group trended toward a lower 24-hour mortality rate (3.9% vs 7.2% for intervention and control, respectively, p=0.25), 48-hour mortality rate (6.3% vs 7.2% for intervention and control, respectively, p=0.76), and 28-day mortality rate (6.3% vs 10.4% for intervention and control, respectively, p=0.23). There was no significant difference observed in known adverse events associated with TXA administration in the prehospital intervention group and control group. A reduction in total blood product usage was observed following the administration of TXA (control: 6.95 units; intervention: 4.09 units; p=0.01).ConclusionPreliminary evidence from the Cal-PAT study suggests that TXA administration may be safe in the prehospital setting with no significant change in adverse events observed and an associated decreased use of blood products in cases of trauma-induced hemorrhagic shock. Given the current sample size, a statistically significant decrease in mortality was not observed. Additionally, this study demonstrates that it may be feasible for paramedics to identify and safely administer TXA in the prehospital setting.

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Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Tranexamic Acid in Prehospital Traumatic Hemorrhagic Shock: Outcomes of the Cal-PAT Study

Dong

et al. 2017

WestJEM

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“…13 The dose-response relationship of TXA was examined by Horrow et al, 14 who concluded that 10 mg/kg followed by 1 mg/kg/hour decreases bleeding after extracorporeal circulation and that larger doses did not provide any additional haemostatic benefit.…”

Section: Dose Selectionmentioning

confidence: 99%

“…Studies in cardiac surgery have noted that a 10 mg/kg-loading dose of TXA followed by an infusion of 1 mg/kg/hour produces plasma concentrations sufficient to inhibit fibrinolysis, and that a larger dose does not provide any additional haemostatic benefit. 13,14 In emergency situations, the administration of a fixed dose is practicable since determining the weight of a seriously injured patient can be difficult. We therefore selected a fixed dose within the range shown to inhibit fibrinolysis and provide haemostatic benefit that would be efficacious for larger patients (> 100 kg) but also safe in smaller patients (< 50 kg), to the extent that the dose per kg that smaller patients would receive has been used in surgical trials without adverse effects.…”

Section: One-way Sensitivity Analysismentioning

confidence: 99%

“…13 The dose-response relationship of tranexamic acid was examined by Horrow et al (1995) who concluded that 10 mg/kg followed by 1 mg/kg/hour decreases bleeding after extracorporeal circulation and that larger doses did not provide any additional haemostatic benefit. 14 In this emergency situation, administration of a fixed dose would be more practicable as determining the weight of a patient would be impossible. Therefore, a fixed dose within the dose range which has been shown to inhibit fibrinolysis and provide haemostatic benefit is being used for this trial.…”

Section: Dose Selectionmentioning

confidence: 99%

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The CRASH-2 trial: a randomised controlled trial and economic evaluation of the effects of tranexamic acid on death, vascular occlusive events and transfusion requirement in bleeding trauma patients

Roberts

Shakur²,

Coats³

et al. 2013

Health Technol Assess

570

399

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Reports are published in Health Technology Assessment (HTA) if (1) they have resulted from work for the HTA programme, and (2) they are of a sufficiently high scientific quality as assessed by the reviewers and editors.Reviews in Health Technology Assessment are termed 'systematic' when the account of the search appraisal and synthesis methods (to minimise biases and random errors) would, in theory, permit the replication of the review by others. HTA programmeThe HTA programme, part of the National Institute for Health Research (NIHR), was set up in 1993. It produces high-quality research information on the effectiveness, costs and broader impact of health technologies for those who use, manage and provide care in the NHS. 'Health technologies' are broadly defined as all interventions used to promote health, prevent and treat disease, and improve rehabilitation and long-term care.The journal is indexed in NHS Evidence via its abstracts included in MEDLINE and its Technology Assessment Reports inform National Institute for Health and Clinical Excellence (NICE) guidance. HTA research is also an important source of evidence for National Screening Committee (NSC) policy decisions.For more information about the HTA programme please visit the website: http://www.hta.ac.uk/ This reportThe research reported in this issue of the journal was funded by the HTA programme as project number 06/303/20. The contractual start date was in April 2007. The draft report began editorial review in January 2012 and was accepted for publication in August 2012. The authors have been wholly responsible for all data collection, analysis and interpretation, and for writing up their work. The HTA editors and publisher have tried to ensure the accuracy of the authors' report and would like to thank the reviewers for their constructive comments on the draft document. However, they do not accept liability for damages or losses arising from material published in this report.This report presents independent research funded by the National Institute for Health Research (NIHR). The views and opinions expressed by authors in this publication are those of the authors and do not necessarily reflect those of the NHS, the NIHR, NETSCC, the HTA programme or the Department of Health. Background: Among trauma patients who survive to reach hospital, exsanguination is a common cause of death. A widely practicable treatment that reduces blood loss after trauma could prevent thousands of premature deaths each year. The CRASH-2 trial aimed to determine the effect of the early administration of tranexamic acid on death and transfusion requirement in bleeding trauma patients. In addition, the effort of tranexamic acid on the risk of vascular occlusive events was assessed.

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“…The first was to define an appropriate effective dose. There is only one study investigating a dose-response relationship [3]. This article showed a plateau effect on drains losses with a total dose of 3 grams tranexamic acid but with no observed effect on transfusions.…”

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confidence: 98%

Tranexamic acid in cardiac surgery: is there a cause for concern?

Royston

2010

Critical Care

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The withdrawal of marketing approval for aprotinin resulted in more clinicians administering tranexamic acid to patients at increased risk of bleeding and adverse outcome. The latest in a series of retrospective analyses of observational data is published in Critical Care and suggests an increase in mortality, when compared to data from the aprotinin era, in those patients having surgery when a cardiac chamber is opened. The added observation of an increase in cerebral excitatory phenomena (seizure activity) with tranexamic acid has a known mechanism and questions if such patients should be given this drug.

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The Dose-Response Relationship of Tranexamic Acid

Abstract: Prophylactic tranexamic acid, 10 mg.kg-1 followed by 1 mg.kg-1.h-1, decreases bleeding after extracorporeal circulation. Larger doses do not provide additional hemostatic benefit.

Cited by 273 publications

References 40 publications

Efficacy and Safety of Tranexamic Acid in Prehospital Traumatic Hemorrhagic Shock: Outcomes of the Cal-PAT Study

Efficacy and Safety of Tranexamic Acid in Prehospital Traumatic Hemorrhagic Shock: Outcomes of the Cal-PAT Study

The CRASH-2 trial: a randomised controlled trial and economic evaluation of the effects of tranexamic acid on death, vascular occlusive events and transfusion requirement in bleeding trauma patients

Tranexamic acid in cardiac surgery: is there a cause for concern?

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