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M2E Too! Mellick's Multimedia EduBlog

The M2E Too! Blog by Larry Mellick, MD, presents important clinical pearls using multimedia.

By its name, M2E Too! acknowledges that it is one of many emergency medicine blogs, but we hope this will serve as a creative commons for emergency physicians.

Friday, February 1, 2019

TXA a Late Bloomer in Bleeding Management

‚ÄčTranexamic acid (TXA) was invented by a Japanese husband-and-wife research team in the 1960s. Years earlier, this same research team had discovered epsilon-aminocaproic acid, a derivative and an analogue of the amino acid lysine. In their search for a more potent antifibrinolytic agent, they discovered tranexamic acid, a synthetic analog of the amino acid lysine. Tranexamic acid is eight to 10 times more powerful than epsilon-aminocaproic acid.

The antifibrinolytic actions of TXA result from the binding of four or five lysine receptor sites on plasminogen. This binding prevents plasmin from binding to and degrading fibrin, preserving fibrin's matrix structure. Initially, marketing of the drug was for mild bleeding such as heavy menstrual periods and dental extractions. Currently, it is used in surgery to decrease the need for blood transfusions by decreasing bleeding and blood loss.

Relatively recently, respectability for this old drug dramatically increased when the 2011 CRASH-2 trial showed that TXA safely and dramatically reduced mortality in bleeding trauma patients. (Lancet 2010;376[9734]:23; http://bit.ly/2CoZJB4.) When treatment was initiated within three hours of injury, the risk of hemorrhage death was reduced by about one-third. Another piece of evidence for the respected stature of this inexpensive and highly cost-effective drug is its inclusion in the WHO list of essential medicines. (http://bit.ly/2CqEpLx.)

More recently, topical tranexamic acid has been used to successfully reduce bleeding in multiple surgical conditions. Successful treatment with topical applications has been reported for stomach bleeding with colostomies, gastrointestinal bleeding, uterine bleeding, and orthopedic and oral surgery, to name a few. Oral bleeding has been successfully managed in patients with hemophilia or Von Willebrand disease undergoing minor oral surgery or dental extractions. Topical application of tranexamic acid is considered safer because it is not absorbed systemically, reducing the risk of thromboembolic disease. Nevertheless, even with parenteral administration of TXA, the risk of thromboembolic disease appears relatively low.

More recently, the successful application of TXA for epistaxis has been reported. Additionally, case reports show success using TXA to manage epistaxis with rivaroxaban for hemophilia and hereditary hemorrhagic telangiectasia. Two studies by Zahed, et al., randomized patients with epistaxis to treatment with topical tranexamic acid or anterior nasal packing (ANP). (Am J Emerg Med 2013;31[9]:1389; Acad Emerg Med 2018;25[3]:261; http://bit.ly/2T0HKGQ.) They were markedly positive in favor of topical TXA (500 mg in 5 mL). Bleeding stopped remarkably sooner with TXA, and discharge from the ED was faster. Rebleeding in the ANP group was significantly greater: Rebleeding during the first 24 hours in the 2018 study was reported in five percent and 10 percent of patients in the TXA and ANP groups, respectively. (Acad Emerg Med 2018;25[3]:261; http://bit.ly/2T0HKGQ.) At one week, rebleeding had occurred in five percent of patients in the TXA group and 21 percent of those in the ANP group.

Undoubtedly, tranexamic acid can be administered topically for epistaxis in multiple ways. Dripping TXA into the nostrils with a syringe or the shortened tubing of a butterfly needle are simple and effective delivery methods. Two other possible options are demonstrated in the videos. After insertion into the nostrils, nasal tampons can be expanded with tranexamic acid or a TXA-oxymetazoline combination. TXA can also be administered topically by using an atomizer without any form of nasal packing. About 1-2 mL (100 to 200 mg of tranexamic acid) can be nebulized in the offending nostrils. This technique appears to be highly effective at widely distributing the medication throughout the nostrils.


Watch this video to see TXA administered for recurring epitaxis.

mellick-TXA nose bleed 2.jpg

Watch this video to see administration of oxymetazoline and TXA for a nosebleed emergency.