Introduction

  • Tranexamic acid (TXA) is a synthetic lysine derivative that inhibits fibrinolysis by blocking the lysine-binding sites on plasminogen.
  • Plasminogen is the inactive precursor of plasmin, the enzyme that dissolves fibrin clots. By preventing plasminogen activation, TXA stabilizes clots and reduces bleeding.

Clinical Detail

PropertyTranexamic Acid (TXA)
Dose
  • Epistaxis: 500–1000 mg via topical nasal gauze
  • Heavy menstrual bleeding: 1.3 g PO TID
  • Hemoptysis: 500 mg via nebulizer
Formulation
  • IV: 1000 mg / 10 mL vial
  • Tablet: 650 mg
PK/PD
  • Onset (IV): 1–5 hours
  • Time to peak concentration: PO 2.5–3 hours; IV 5 minutes
  • Duration: PO 24 hours; IV 17 hours
  • Excretion: urine (>95% as unchanged drug)
Adverse effectsRapid administration may cause hypotension.
Drug interactions & warningsUse caution in women taking oral contraceptives, patients with clotting disorders, and those taking chlorpromazine.
CompatibilityCompatible with normal saline and dextrose solutions.
Directions by indication
  • Anterior epistaxis: consider 500–1000 mg of TXA (5–10 mL) to soak gauze/pledget and insert into the nasal cavity for ~30 min.
  • Heavy menstrual bleeding: consider 1300 mg oral TXA TID for up to 5 days during menstruation (per the oral TXA label).

Evidence

StudyIndicationInterventionOutcome
Heavy Menstrual Bleeding
Bryant-Smith 2018
(Cochrane SR)
PMID 29656433		Heavy menstrual bleedingTXA vs placebo / NSAIDReduced menstrual blood loss by ~53 mL/cycle vs placebo (mean difference −53.2 mL).
Lukes 2010
(RCT)
PMID 20859150		Heavy menstrual bleedingTXA 1.3 g PO TIDReduced menstrual blood loss (−69.6 mL, 40.4%) and improved quality of life vs placebo.
Dental / Oral & Other
Zirk 2018
(retrospective cohort, n=542)
PMID 29627368		Oral / dental bleeding (anticoagulated)Topical TXA-soaked gauze~1.6× greater chance of stopping oral bleeding vs gauze alone.
Nuvvula 2014
(RCT)
PMID 24808695		Gingival bleeding in hemophiliaTXA mouthwashEffective alternative to factor replacement for controlling gingival bleeding.
Wand 2018
(RCT)
PMID 30321510		Hemoptysis (non-massive)Nebulized TXA 500 mg TID vs saline
  • Hemoptysis resolution within 5 days 96% vs 50%.
  • Shorter length of stay and fewer invasive procedures.
Epistaxis — evidence is MIXED
Zahed 2013
(single-center RCT)
PMID 23911102		Anterior epistaxisTopical TXA 500 mg/5 mL vs anterior nasal packingBleeding stopped ≤10 min in 71% vs 31.2%; faster discharge.
Zahed 2018
(single-center RCT)
PMID 29125679		Epistaxis on antiplatelet agentsTopical TXA vs anterior nasal packingBleeding stopped at 10 min in 73% vs 29%; less rebleeding at 1 week.
NoPAC / Reuben 2021
(multicenter RCT, n=496, 26 EDs)
PMID 33612282		Anterior epistaxisTopical TXA vs placeboNo difference in need for nasal packing (43.7% vs 41.3%, not significant) — the largest, most rigorous epistaxis RCT.

Note: the epistaxis evidence is mixed. Small single-center RCTs (Zahed 2013, 2018) favored topical TXA, but the larger multicenter NoPAC RCT (Reuben 2021) found no benefit over placebo for reducing nasal packing.

Conclusions

  • TXA reduces blood loss in heavy menstrual bleeding, supported by strong randomized controlled trial and systematic-review evidence.
  • It is a useful adjunct for dental/oral bleeding (including in anticoagulated and hemophilia patients) and for non-massive hemoptysis.
  • For anterior epistaxis the evidence is mixed: small single-center RCTs suggested benefit, but the larger multicenter NoPAC RCT found topical TXA no better than placebo for reducing nasal packing. TXA should not be considered clearly effective for epistaxis.
  • Apply caution in patients with clotting disorders, those on oral contraceptives, and with rapid IV administration (risk of hypotension); match the route and dose to the indication.

References

  • Tranexamic acid. Micromedex [Electronic version]. Greenwood Village, CO: Truven Health Analytics.
  • Bryant-Smith AC, et al. Antifibrinolytics for heavy menstrual bleeding. Cochrane Database Syst Rev. 2018 Apr 15;4(4):CD000249. PMID: 29656433.
  • Lukes AS, et al. Tranexamic acid treatment for heavy menstrual bleeding: a randomized controlled trial. Obstet Gynecol. 2010 Oct;116(4):865-75. PMID: 20859150.
  • Zirk M, et al. Supportive topical tranexamic acid application for hemostasis in oral bleeding events — retrospective cohort study of 542 patients. J Craniomaxillofac Surg. 2018 Jun;46(6):932-936. PMID: 29627368.
  • Nuvvula S, et al. Efficacy of tranexamic acid mouthwash as an alternative for factor replacement in gingival bleeding during dental scaling in cases of hemophilia: a randomized clinical trial. Contemp Clin Dent. 2014 Jan-Mar;5(1):49-53. PMID: 24808695.
  • Zahed R, et al. A new and rapid method for epistaxis treatment using injectable form of tranexamic acid topically: a randomized controlled trial. Am J Emerg Med. 2013 Sep;31(9):1389-92. PMID: 23911102.
  • Zahed R, et al. Topical tranexamic acid compared with anterior nasal packing for treatment of epistaxis in patients taking antiplatelet drugs: randomized controlled trial. Acad Emerg Med. 2018 Mar;25(3):261-266. PMID: 29125679.
  • Reuben A, et al. The use of tranexamic acid to reduce the need for nasal packing in epistaxis (NoPAC): randomized controlled trial. Ann Emerg Med. 2021 Jun;77(6):631-640. doi:10.1016/j.annemergmed.2020.12.013. PMID: 33612282.
  • Janapala RN, et al. Efficacy of topical tranexamic acid in epistaxis: a systematic review and meta-analysis. Am J Emerg Med. 2021;51:169-175. doi:10.1016/j.ajem.2021.10.043. PMID: 34763235.
  • Wand O, et al. Inhaled tranexamic acid for hemoptysis treatment: a randomized controlled trial. Chest. 2018 Dec;154(6):1379-1384. PMID: 30321510.
  • Solomonov A, et al. Pulmonary hemorrhage: a novel mode of therapy. Respir Med. 2009 Aug;103(8):1196-200. PMID: 19251406.
  • How to place an epistaxis TXA pack (instructional video). https://www.youtube.com/watch?v=ekGsM9CZSpY
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