Pharm

Tranexamic Acid

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Tranexamic Acid, Lysteda, Cyklokapron, TXA

  • Indications
  1. Life-Threatening Hemorrhage (first 3 hours)
    1. Some EMS services are initiating Tranexamic Acid in the field (esp. >45 min from Level I Trauma)
    2. rTEGLy30 (Lysis Time) >3% in first 3 hours after injury
    3. Subarachnoid Hemorrhage (Anticoagulant Reversal)
    4. Massive Hemorrhage with refractory bleeding and cardiovascular collapse
      1. Hypotension in the Dialysis Patient
      2. Acute Gastrointestinal Hemorrhage
      3. Postpartum Hemorrhage
  2. Acute Localized Bleeding
    1. Menorrhagia Management (taken orally)
    2. Refractory Epistaxis (topical to nares atomized)
    3. Control of Hemorrhage after Tonsillectomy (gargled)
    4. Dental procedure bleeding (topical to Gingiva)
    5. Hemoptysis
    6. Intraoperative bleeding management (e.g. CABG, liver transplant, THA, TKA)
  3. Prophylaxis of bleeding
    1. Tooth Extraction in patients with Hemophilia or other Coagulopathy
  • Contraindications
  1. Hypersensitivity to Tranexamic Acid
  2. Not approved for pediatric Hemorrhage
  3. Subarachnoid Hemorrhage
  4. Thromboembolism (venous or arterial)
  5. Concurrent thrombosis management
  6. Concurrent Seizure activity
  7. Concurrent factor concetrate (Cryoprecipitate) administration
  8. Disseminated Intravascular Coagulation
  9. Macroscopic Hematuria
  10. Color Blindness (TXA is associated with Vision changes in this cohort)
  11. Exercise caution with those on Oral Contraceptives (venous thrombosis risk)
  • Background
  1. Tranexamic Acid (TXA) is a synthetic derivative of the amino acid lysine
  2. Tranexamic Acid-like agents are found in tea
    1. Hence the reason tea bags may be used topically to slow dental bleeding
  • Mechanism
  1. Tranexamic Acid (TXA) is an antifibrinolytic that prevents plasminogen activation
  2. TXA reversibly attaches and blocks at the plasminogen lysine binding site
  3. Plasmin may still be formed by endogenous tPA, but the plasmin formed is inactive
  4. Fibrin clot is therefore stabilized by preventing plasmin mediated Fibrinolysis
  • Pharmacokinetics
  1. Excreted in urine unchanged
  2. Half-life: 2 hours
  3. No dose adjustment needed in hepatic or renal disease
  • Dosing
  • Tranexamic Acid for Life Threatening Hemorrhage
  1. Tranexamic Acid (TXA) concentration: 100 mg/ml in 10 ml vial
  2. Adults
    1. Initial: Tranexamic Acid (TXA) 1 g over 10 minutes
      1. Maximum infusion rate 100 mg/min to prevent Hypotension
      2. If Hypotension occurs, extend infusion to 20 minutes
    2. Next (if Serum Creatinine <3 g/dl)
      1. Tranexamic Acid Infusion at 1 g (10 ml) in 250 ml NS infused at 32 ml/h over 8 hours OR
      2. Repeat dose 1 g over 10 minutes at 8 hours after first
    3. Hospital administration
      1. Add 1 g TXA (10 ml) to 50 ml bag NS
    4. Prehospital administration
      1. EMS dilutes 10 ml TXA in 50 ml Normal Saline bag
      2. Runs via 10 cc/ml tubing at 1 drip/second
  3. Child:
    1. Bolus: 15 mg/kg up to 1000 mg over 10 minutes
    2. Infusion: 2 mg/kg/h for 8 hours or until bleeding stops
    3. Safe and effective in children
      1. Eckert (2014) J Trauma Acute Care Surg 77(6): 852-8 +PMID:25423534 [PubMed]
  • Dosing
  • Routine Uses (ambulatory or prophylactic)
  1. Prophylaxis before Tooth Extraction in Hemophilia
    1. Immediately before surgery
      1. Tranexamic Acid 10 mg/kg IV
    2. Following surgery
      1. Tranexamic Acid 10 mg/kg orally three to four times daily for 2-8 days
      2. (2014) Tarascon Pharmacopoeia
  2. Oral (Lysteda for Menorrhagia)
    1. Take two 650 mg tabs (1.3 g) orally three times daily for the first 5 days of the Menstrual Cycle
    2. More expensive than other options for Menorrhagia
  3. Topical (using IV form, experimental, not FDA approved)
    1. Epistaxis
      1. Tranexamic Acid IV form applied topically to nasal septum (e.g. cotton pledgets, atomizer, rhino rocket)
      2. Zahed (2013) am j emerg med 31(9): 1389-92 [PubMed]
    2. Dental Procedure Bleeding
      1. Local bleeding control for patients on Perioperative Anticoagulation
    3. Postoperative Bleeding after Tonsillectomy
      1. Gargled Tranexamic Acid (TXA) 5% Mouthwash
      2. Prepare Tranexamic Acid (TXA) 5% Mouthwash
        1. Tranexamic Acid (TXA) is available in 1000 mg/10 ml vials that contain 10 ml
        2. Prepare 2 small cups each of 5 ml TXA (500 mg) and 5 ml cold water (10 ml of diluted TXA per cup)
        3. Alternatively a 500 mg TXA tablet may be dissolved in 10-15 ml water
      3. Instructions
        1. Have patient gargle 10 ml for 1-2 minutes and then gently spit out solution
        2. May repeat again in 10-15 minutes
      4. References
        1. https://rebelem.com/topical-tranexamic-acid-epistaxis-oral-bleeds/
  1. Most effective when given in first hour of severe Hemorrhage
    1. Unlikely to offer benefit at 3 hours or longer from Hemorrhage onset and may be harmful
    2. Inexpensive ($100) when compared with other measures used in Hemorrhage Management
  2. References
    1. CRASH-2
      1. Small mortality benefit if used in first hour of refractory Hemorrhage and surgery delayed
      2. NNT 67 with a 1.5% all-cause mortality reduction at 28 days (and no significant adverse effects)
      3. No increased risk of Venous Thromboembolism
      4. (2010) Lancet 376(9734): 23-32 [PubMed]
      5. Roberts (2011) Lancet 377(9771):1096-101 [PubMed]
    2. CRASH-3
      1. Head Injury Related Mortality decreased 1.5% (but no change in all-cause mortality)
      2. (2019) Lancet 394(10210):1713-23 +PMID:31623894 [PubMed]
    3. Number Needed to Treat in the most seriously bleeding patients: 7
      1. Morrison (2013) JAMA Surg 148(3): 218-25 [PubMed]
    4. Postpartum Hemorrhage
      1. No significant benefit of TXA
      2. Decreased Hemorrhage related mortality 0.4% (but no change in all cause mortality)
      3. (2017) Lancet 389(10084):2105-16 +PMID:28456509 [PubMed]
  • Efficacy
  • Localized Bleeding
  1. Menorrhagia
    1. More effective than NSAIDs
  2. Hemoptysis
    1. Inhaled Tranexamic Acid is assoicated with faster resolution of mild to moderate Hemoptysis
    2. Wand (2018) Chest 154(6):1379-84 +PMID: 30321510 [PubMed]
  3. Epistaxis
    1. TXA is superior to Lidocaine with Epinephrine (limited data to small studies)
  • Adverse Effects
  1. Thrombosis risk (no longer considered a risk)
    1. Initial study concern
    2. Follow-up studies demonstrated no significant increased risk of thrombosis (DVT, PE)
    3. Increased thrombosis risk may occur in Disseminated Intravascular Coagulation (DIC)
  2. Hypotension (Intravenous TXA)
    1. Avoid rapid TXA rapid IV injection
  3. Nausea or Vomiting
  4. Vision change (Blurred Vision, altered color Vision)
  5. Diarrhea
  6. Back pain
  7. Myalgias
  8. Headache
  • Drug Interactions
  1. Prothrombin Complex Concentrate
    1. Co-administration with TXA may increase thrombosis risk
  2. Factor 9 Complex Concentrate
    1. Co-administration with TXA may increase thrombosis risk
  • Safety
  1. Pregnancy Category B
  • References
  1. (2016) CALS Manual, 14th ed, 1:69
  2. Mell in Herbert (2015) EM:Rap 15(1): 1-2
  3. Freeman and Bourland (2021) Crit Dec Emerg Med 35(12): 3-11
  4. Lovecchio (2017) Crit Dec Emerg Med 31(9):24
  5. Pescatore and Swaminathan in Herbert (2021) EM:Rap 21(4): 14-5