Tranexamic Acid

Reviewed and revised 24 May 2014

OVERVIEW

  •  anti-fibrinolytic agent with many uses in preventing haemorrhage that rose to prominence following the CRASH-2 study showing a mortality benefit in trauma patients

CLASS

  • anti-fibrinolytic derivative of lysine

MECHANISM OF ACTION

  • interferes with the normal fibrinolysis process
  • competitive inhibits activation of plasminogen through reversible interactions with lysine-binding sites on the enzyme
  • non-competitively inhibits plasmin at higher concentrations
  • 10-fold greater potency than aminocaproic acid in vitro

PHARMACEUTICS

  • injection: clear, colourless solution, 500mg in 5ml
  • tablets: 500mg
  • syrup: 100mg/mL
  • 5% mouthwash can be made by crushing a 500mg tablet and dissolving in 10 mL of water immediately before use

DOSE

  • PO: 1g Q6h for 3-4d for menorrhagia
  • IV: 20mg/kg over 5min; in trauma 1g over 10 min then 1g over 8h IV
  • TOPICAL: pledgets/ gauze soaked in IV solution can be applied to sites of epistaxis
  • 10 mL of 5% mouthwash held in mouth near bleeding site for exactly 2 minutes (no gargling), 5 times daily for 7 days (if needed)
  • decrease in renal impairment, no change need in hepatic impairment

INDICATIONS

  • decrease peri-operative bleeding (e.g. prior to repeat cardiac surgery, total knee arthroplasty and total hip arthroplasty)
  • reverse thrombolytic therapy
  • menorrhagia
  • dental bleeding (treatment, also prevention for dental extraction in hemophilia)
  • epistaxis
  • hemoptysis
  • hyphaema (decrease rates of rebleeds)
  • hereditary angioneurotic oedema
  • hemorrhagic shock (trauma, surgical hemorrhage and obstetric hemorrhage)
  • adjunctive therapy for NOACs (benefit uncertain)

CONTRA-INDICATIONS

May include:

  • Active intravascular clotting (contraindicated)
  • Subarachnoid hemorrhage, (may increase cerebral ischaemic complications)
  • Hypersensitivity to tranexamic acid
  • Upper renal tract bleeding,(relatively contraindicated due to the possibility of clot retention)

Caution in patients at risk of thrombotic complications, e.g. procoagulant disorders, previous DVT / PE, (increases risk of thrombotic adverse effects)

PREGNANCY

  • B1 category

ADVERSE EFFECTS

  • myopathy
  • hypotension (usually with rapid IV injection)
  • intravascular thrombosis
  • thrombin time increases
  • GI disturbance (N&V, diarrhoea, dyspepsia) when taken orally
  • allergic reactions (rare)
  • disturbance of colour vision

PHARMACOKINETICS

  • Absorption – oral bioavailability 34%
  • Distribution — no albumin binding, 3% plasma protein binding at therapeutic levels (due to binding plasmin)
  • Metabolism – minimal
  • Elimination – renal t1/2 = 2 hrs; >90% eliminated at 24h following an IV bolus

EVIDENCE

Trauma

Cardiac surgery

-> decreases transfusion rate in cardiac surgery & no difference in re-operation rates
-> no change in outcome

BART – blood conservation using antifibrinolytics, NEJM 2008 358(22)

  • Aprotinin vs epsilon-aminocaproic acid vs tranexamic acid
  • Aprotinin increased risk of death (absolute 2%), from cardiogenic shock / CHF / MI (x2), from stroke (?), renal failure (not significant)
  • Only trend in reduced bleeding with Aprotinin
  • Study ceased early
  • Aprotinin (Trasylol) withdrawn from market by Bayer

AN APPROACH

  • use as part of massive transfusion protocol and in bleeding trauma patients
  • may be used in cardiac surgery
  • useful for epistaxis, dental bleeding and menorrhagia

CCC 700 6

Critical Care

Compendium

Chris is an Intensivist and ECMO specialist at the Alfred ICU in Melbourne. He is also the Innovation Lead for the Australian Centre for Health Innovation at Alfred Health and Clinical Adjunct Associate Professor at Monash University. He is a co-founder of the Australia and New Zealand Clinician Educator Network (ANZCEN) and is the Lead for the ANZCEN Clinician Educator Incubator programme. He is on the Board of Directors for the Intensive Care Foundation and is a First Part Examiner for the College of Intensive Care Medicine. He is an internationally recognised Clinician Educator with a passion for helping clinicians learn and for improving the clinical performance of individuals and collectives.

After finishing his medical degree at the University of Auckland, he continued post-graduate training in New Zealand as well as Australia’s Northern Territory, Perth and Melbourne. He has completed fellowship training in both intensive care medicine and emergency medicine, as well as post-graduate training in biochemistry, clinical toxicology, clinical epidemiology, and health professional education.

He is actively involved in in using translational simulation to improve patient care and the design of processes and systems at Alfred Health. He coordinates the Alfred ICU’s education and simulation programmes and runs the unit’s education website, INTENSIVE.  He created the ‘Critically Ill Airway’ course and teaches on numerous courses around the world. He is one of the founders of the FOAM movement (Free Open-Access Medical education) and is co-creator of litfl.com, the RAGE podcast, the Resuscitology course, and the SMACC conference.

His one great achievement is being the father of two amazing children.

On Twitter, he is @precordialthump.

| INTENSIVE | RAGE | Resuscitology | SMACC

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