Using TXA for Traumatic Bleeds

Tranexamic acid (TXA) is an old, inexpensive drug that surgeons have been quietly using for decades during surgery to reduce perioperative bleeding. TXA has recently garnered international attention for its role in reducing mortality from trauma-related hemorrhage, a major cause of death worldwide. In addition, TXA shows promise for use in other bleeding conditions commonly seen in the ED, such as epistaxis and bleeding after dental extractions. Here is everything you need to know as an emergency physician about TXA.

How It Works
TXA acid is an antifibrinolytic drug which is thought to act as a clot stabilizer. A synthetic derivative of the amino acid lysine, it blocks the lysine binding site on plasminogen, preventing activation of plasmin and inhibiting the breakdown of fibrin clot [^1]. TXA comes in both intravenous and oral formulations.

Notable History
TXA is used to reduce perioperative bleeding in patients undergoing orthopedic and cardiac surgery, and to reduce hemorrhage in major trauma. Oral TXA is effective in decreasing heavy menstrual bleeding, and to reduce rebleeding rates in traumatic hyphema [^1]. A TXA mouthwash is also used to reduce bleeding in patients on oral anticoagulants undergoing dental extractions [^2]. Newer indications for TXA include topical use in epistaxis, and well as direct applications to bleeding surfaces during surgery [^3,4]. TXA is also being investigated for use in postpartum hemorrhage, a major cause of maternal mortality in developing countries [^5].

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Specific Uses for TXA
Trauma-related hemorrhage: The CRASH-2 trial, originally published in Lancet in 2010, was a large multicenter trial including over 20,000 patients from 40 countries. Interestingly, the U.S. was conspicuously absent, since no large drug companies would fund a study of this inexpensive drug. Adult trauma patients presenting within 8 hours of injury with or at risk for significant hemorrhage were randomized in a double-blind fashion to receive either intravenous TXA or placebo. TXA was associated with reduced all-cause mortality (14.5 % in TXA group versus 16.0 % in placebo group; relative risk 0.91; 95 % CI 0.85 – 0.97; p = 0.0035) and reduced risk of death due to bleeding (4.9 % in TXA group versus 5.7 % in placebo group; relative risk 0.85, 95 % CI 0.76 – 0.96; p = 0.0077). A subgroup analysis showed that TXA was most effective when given within the first 3 hours, and that later treatment was unlikely to be effective and may even be harmful [^6].

Epistaxis: A recent study showed that patients with epistaxis treated with topical TXA (cotton pledget soaked in injectable form of TXA and placed in affected nostril) had a quicker time to epistaxis resolution, reduced ED length of stay, decreased rebleeding rate, and increased patient satisfaction compared to those treated with anterior nasal packing. Within 10 minutes of treatment, bleeding had stopped in 71% of patients in the TXA group, compared to 31% of patients in the nasal packing group (odds ratio 2.27; 95 % CI 1.68 – 3.06; p < 0.001).³ Successful use of nebulized TXA has also been reported to control epistaxis in a patient with an invasive airway malignancy [^7].

Minor mucous membrane and cutaneous bleeding: TXA mouthwash can be used for bleeding after dental procedures. If the mouthwash is not available, a paste can be made by crushing 3 TXA tablets and mixing with small aliquots of sterile water, and applying to sites of minor bleeding, such as dental extraction sites, scalp lacerations, and extremity lacerations [^8].

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Adverse Events
Venous and arterial thromboembolism have been reported after TXA use, although rarely. Hypotension can occur with rapid IV injection. Headache, abdominal pain, muscle pain, and nasal/sinus symptoms have been reported with oral administration [^1].

Cautions
Because TXA is a antifibrinolytic agent, it is contraindicated in patients with active thromboembolic disease, and should be used with caution in patients with a history of thromboembolic disease [^1].

Dosing and Adjustments

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• Trauma-related hemorrhage: 1000 mg IV over 10 minutes loading dose, followed by 1000 mg IV administered over 8 hours [^6].
• Cyclic heavy menstrual bleeding: 1300 mg PO 3 times daily for up to 5 days during menses [^1]
• Epistaxis: Cotton pledget soaked in the injectable form of TXA (500 mg in 5 mL) is inserted into affected nostril [^3]
• Tooth extraction in patients with hemophilia (in combination with appropriate factor replacement): 10 mg/kg IV [^1]
• Prevention of dental procedure bleeding in patients on oral anticoagulant therapy: Oral rinse 4.8% solution. Hold 10 mL in mouth and rinse for 2 minutes, then spit out [^1]
• Traumatic hyphema: 25 mg/kg PO 3 times daily for 5-7 days [^1]
• Prevention of perioperative bleeding during orthopedic and cardiac surgery: IV dosing varies based on procedure

Special Considerations
TXA is pregnancy category B. While adverse events have not been observed in animal reproduction studies, there are no adequate studies in human subjects, and TXA is known to cross the placenta. TXA is excreted in breast milk. Risks of infant exposure, benefits of breastfeeding for the infant, and benefits of treatment to the mother should be weighed when deciding to continue or discontinue breastfeeding while taking TXA [^1].

Cost

• Intravenous solution 1000 mg/10 mL (10 mL): $36.84
• Oral tablets 650 mg (30 tablets): $156.43 [1]

Bottom Line For Emergency Physicians:

1. Give intravenous TXA in trauma with confirmed or suspected major hemorrhage. Earlier treatment is better, and use 3 hours after injury may not be effective and may increase harm.
2. Consider topical TXA for epistaxis or minor bleeding from dental extractions or lacerations.

REFERENCES

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1. Lexicomp: Tranexemic acid. available at www.uptodate.com. accessed september 22, 2016.
2. Sindet-Pedersen S, Ramström G, Bernvil S, Blombäck M. Hemostatic effect of tranexamic acid mouthwash in anticoagulant-treated patients undergoing oral surgery. N Engl J Med. 1989;320(13):840-843.
3. Zahed R, Moharamzadeh P, Alizadeharasi S, Ghasemi A, Saeedi M. A new and rapid method for epistaxis treatment using injectable form of tranexamic acid topically: A randomized controlled trial. Am J Emerg Med. 2013;31(9):1389-1392. doi: 10.1016/j.ajem.2013.06.043 [doi].
4. Ker K, Beecher D, Roberts I. Topical application of tranexamic acid for the reduction of bleeding. Cochrane Database Syst Rev. 2013;(7):CD010562. doi(7):CD010562. doi: 10.1002/14651858.CD010562.pub2 [doi].
5. Shakur H, Elbourne D, Gülmezoglu M, et al. The WOMAN trial (world maternal antifibrinolytic trial): Tranexamic acid for the treatment of postpartum haemorrhage: An international randomised, double blind placebo controlled trial. . Trials. 2010;11(1):1.
6. CRASH-2 trial collaborators, Shakur H, Roberts I, et al. Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): A randomised, placebo-controlled trial. Lancet. 2010;376(9734):23-32. doi: 10.1016/S0140-6736(10)60835-5 [doi].
7. Hankerson MJ, Raffetto B, Mallon WK, Shoenberger JM. Nebulized tranexamic acid as a noninvasive therapy for cancer-related hemoptysis. J Palliat Med. 2015;18(12):1060-1062.
8. Dietrich S. Academic Life in Emergency Medicine. Trick of the Trade: Topical Tranexamic Acid Paste for Hemostasis Web site. https://www.aliem.com/2016/trick-trade-topical-tranexamic-acid-paste-hemostasis/. Published February 17, 2016. Updated 2016. Accessed October 14, 2016.