Tranexamic acid is a synthetic analog of the amino acidlysine. It serves as an antifibrinolytic by reversibly binding four to five lysine receptor sites on plasminogen. This decreases the conversion of plasminogen to plasmin, preventing fibrin degradation and preserving the framework of fibrin's matrix structure.[5] Tranexamic acid has roughly eight times the antifibrinolytic activity of an older analogue, ε-aminocaproic acid.[citation needed] Tranexamic acid also directly inhibits the activity of plasmin with weak potency (IC50 = 87 mM),[6] and it can block the active-site of urokinase plasminogen activator (uPA) with high specificity (Ki = 2 mM), one of the highest among all the serine proteases.[7]
Tranexamic acid is frequently used following major trauma.[13] Tranexamic acid is used to prevent and treat blood loss in a variety of situations, such as dental procedures, heavy menstrual bleeding, and surgeries with high risk of blood loss.[14][15]
Trauma
Tranexamic acid has been found to decrease the risk of death due to any cause in people who have significant bleeding due to trauma.[16][17][18][19] It is most effective if taken within the first three hours following major trauma.[20] It also decreases the risk of death if given within the first three hours of brain injury.[21]
Menstrual bleeding
Tranexamic acid is sometimes used to treat heavy menstrual bleeding.[15] When taken by mouth it both safely and effectively treats regularly occurring heavy menstrual bleeding and improves quality of life.[5][22][23] Another study demonstrated that the dose does not need to be adjusted in females who are between ages 12 and 16.[5]
Childbirth
Tranexamic acid is sometimes used (often in conjunction with oxytocin) to reduce bleeding after childbirth.[24] Death due to postpartum bleeding is reduced in women receiving tranexamic acid.[3]
Surgery
Tranexamic acid is sometimes used in orthopedic surgery to reduce blood loss, to the extent of reducing or altogether abolishing the need for perioperative blood transfusion. It is of proven value in clearing the field of surgery and reducing blood loss when given before or after surgery. Drain and number of transfusions are reduced.[25][26][27]
In surgical corrections of craniosynostosis in children it reduces the need for blood transfusions.[28]
In spinal surgery (e.g., scoliosis), correction with posterior spinal fusion using instrumentation, to prevent excessive blood loss.[29][30]
In the United States, tranexamic acid is FDA approved for short-term use in people with severe bleeding disorders who are about to have dental surgery.[31] Tranexamic acid is used for a short period of time before and after the surgery to prevent major blood loss and decrease the need for blood transfusions.[32]
Tranexamic acid is used in dentistry in the form of a 5% mouth rinse after extractions or surgery in patients with prolonged bleeding time; e.g., from acquired or inherited disorders.[33]
In China, TXA is allowed in over-the-counter toothpastes, with six products using the drug. As of 2018, there are no limits on dosage, nor requirements for labeling the concentration.[34] 0.05% TXA in toothpaste is allowed OTC in Hong Kong.[35] <5% TXA in over-the-counter toothpaste is first patented and marketed by Lion Corporation in Japan,[36] where it is still sold.[37] Presence of unauthorized TXA has led to the Canadian recall of a Yunnan Baiyao toothpaste in 2019.[38]
Hematology
There is not enough evidence to support the routine use of tranexamic acid to prevent bleeding in people with blood cancers.[39] However, there are several trials that are currently assessing this use of tranexamic acid.[39] For people with inherited bleeding disorders (e.g. von Willebrand's disease), tranexamic acid is often given.[40] It has also been recommended for people with acquired bleeding disorders (e.g., directly acting oral anticoagulants (DOACs)) to treat serious bleeding.[41]
Nosebleeds
The use of tranexamic acid, applied directly to the area that is bleeding or taken by mouth, appears useful to treat nose bleeding compared to packing the nose with cotton pledgets alone.[42][43][44] It decreases the risk of rebleeding within 10 days.[45]
Other uses
Tentative evidence supports the use of tranexamic acid in hemoptysis.[46][47]
In hereditary hemorrhagic telangiectasia - Tranexamic acid has been shown to reduce frequency of epistaxis in patients with severe and frequent nosebleed episodes from hereditary hemorrhagic telangiectasia.[49]
In melasma - tranexamic acid is sometimes used in skin whitening as a topical agent, injected into a lesion, or taken by mouth, both alone and as an adjunct to laser therapy; as of 2017 its safety seemed reasonable but its efficacy for this purpose was uncertain because there had been no large scale randomized controlled studies nor long term follow-up studies.[50][51] It is allowed as a quasi-drug for skin whitening in Japan.[52]
In hyphema - Tranexamic acid has been shown to be effective in reducing risk of secondary hemorrhage outcomes in people with traumatic hyphema.[53]
Experimental uses
Tranexamic acid might alleviate neuroinflammation in some experimental settings.[54]
Tranexamic acid can be used in case of postpartum hemorrhage; it can decrease the risk of death due to bleeding by one third according to the WHO.[55]
Contraindications
Allergic to tranexamic acid
History of seizures
History of venous or arterial thromboembolism or active thromboembolic disease
Severe kidney impairment due to accumulation of the medication, dose adjustment is required in mild or moderate kidney impairment[2]
Adverse effects
Side effects are rare.[4] Some reported adverse events include seizures, changes in color vision, blood clots, and allergic reactions such as anaphylaxis.[4] Whether the risk of venous thromboembolism (blood clots) is actually increased is a matter of debate. The risk is mentioned in the product literature,[5] and they were reported in post marketing experience.[5] Despite this, and the inhibitory effect of tranexamic acid on blood clot breakdown, large studies of the use of tranexamic acid have not shown an increase in the risk of venous or arterial thrombosis,[56][57] even in people who had previously experienced thrombosis under other circumstances.[57]
Special populations
Tranexamic acid is categorized as pregnancy category B. No harm has been found in animal studies.[5]
Small amounts appear in breast milk if taken during lactation.[5] If it is required for other reasons, breastfeeding may be continued.[58]
In kidney impairment, tranexamic acid is not well studied. However, due to the fact that it is 95% excreted unchanged in the urine, it should be dose adjusted in patients with renal impairment.[5]
In liver impairment, dose change is not needed as only a small amount of the drug is metabolized through the liver.[5]
Tranexamic acid is marketed in the U.S. and Australia in tablet form as Lysteda and in Australia, Sweden[60] and Jordan it is marketed in an IV form and tablet form as Cyklokapron, in the UK and Sweden[60] as Cyclo-F. In the UK it is also marketed as Femstrual, in Asia as Transcam, in Bangladesh as Intrax & Tracid, in India as Pause, in Pakistan as Transamin, in South America as Espercil, in Japan as Nicolda, in France, Poland, Belgium and Romania as Exacyl and in Egypt as Kapron. In the Philippines, its capsule form is marketed as Hemostan and in Israel as Hexakapron.[citation needed]
Legal status
The U.S. Food and Drug Administration (FDA) approved tranexamic acid oral tablets (brand name Lysteda) for treatment of heavy menstrual bleeding in November 2009.[61]
In March 2011, the status of tranexamic acid for treatment of heavy menstrual bleeding was changed in the UK, from PoM (Prescription only Medicines) to P (Pharmacy Medicines)[62] and became available over the counter in UK pharmacies under the brand names of Cyklo-F and Femstrual, initially exclusively for Boots pharmacy, which has sparked some discussion about availability.[63] (In parts of Europe it had then been available OTC for over a decade.[61]) Regular liver function tests are recommended when using tranexamic acid over a long period of time.[64]
References
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^ abcdBritish national formulary: BNF 69 (69 ed.). British Medical Association. 2015. p. 170. ISBN9780857111562.
^World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
^Hamilton R (2015). Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition. Jones & Bartlett Learning. p. 415. ISBN9781284057560.
^Melvin JS, Stryker LS, Sierra RJ (2015). "Tranexamic Acid in Hip and Knee Arthroplasty". The Journal of the American Academy of Orthopaedic Surgeons. 23 (12): 732–40. doi:10.5435/JAAOS-D-14-00223. PMID26493971. S2CID41823501.
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^"How to Choose Toothpaste". ion Corporation. if toothpaste has a label of "quasi drug", this indicates that the product contains active ingredients [...] Tranexamic acid
^"Unauthorized". Health Canada. Government of Canada. 4 October 2019. Retrieved 30 July 2020.
^"Tranexamic acid". Clinical Transfusion. International Society of Blood Transfusion (ISBT). Archived from the original on 17 January 2018. Retrieved 16 January 2018.
^Williams A, Biffen A, Pilkington N, Arrick L, Williams RJ, Smith ME, et al. (2017). "Haematological factors in the management of adult epistaxis: systematic review". The Journal of Laryngology and Otology. 131 (12): 1093–1107. doi:10.1017/S0022215117002067. PMID29280698. S2CID45310419.((cite journal)): CS1 maint: overridden setting (link)
^Klepfish A, Berrebi A, Schattner A (2001). "Intranasal tranexamic acid treatment for severe epistaxis in hereditary hemorrhagic telangiectasia". Archives of Internal Medicine. 161 (5): 767. doi:10.1001/archinte.161.5.767. PMID11231712.
^Zhou LL, Baibergenova A (2017). "Melasma: systematic review of the systemic treatments". International Journal of Dermatology. 56 (9): 902–908. doi:10.1111/ijd.13578. PMID28239840. S2CID21683251.
^Chornenki NL, Um KJ, Mendoza PA, Samienezhad A, Swarup V, Chai-Adisaksopha C, et al. (2019). "Risk of venous and arterial thrombosis in non-surgical patients receiving systemic tranexamic acid: A systematic review and meta-analysis". Thrombosis Research. 179: 81–86. doi:10.1016/j.thromres.2019.05.003. PMID31100632. S2CID157066652.
