TXA – Old Drug, New Uses

• TXA or tranexamic acid is an indirect or antifibrinolytic inhibitor. Initially, tranexamic acid was approved for heavy blood loss during menstrual cycles, and genetic bleeding disorders. 
• In short, tranexamic acid aids in the blood clotting process. Those working in trauma may be familiar with TXA, as it is associated with traumatic injuries and major blood loss. 
• TXA has proven to help causes of blood loss during surgeries such as cardiac, epistaxis, dental extractions, gynecological, orthopedic, liver and kidney, oral and maxillofacial surgeries, dermatologic procedures and nebulization in post-tonsillectomy hemorrhage. It even can be repurposed for postpartum hemorrhage. 

Case Study

A 19-year-old female presents to the emergency department (ED) with oral hemorrhage after a recent tonsillectomy. One hour into her ED evaluation, she began bleeding, leaving greater than five hundred milliliters (mL) of blood in the emesis basin. She becomes anxious, pale, diaphoretic and tachycardic at 124 beats per minute (bpm) and hypotensive with a blood pressure of 84/54 mm Hg. She requires frequent oral suctioning for airway protection. Secondary to the large volume of hemorrhage and continued bleeding without the potential for rapid operative intervention, she receives one unit of uncrossmatched packed red blood cells (PRBC) and nebulized TXA 1000 mg / 10 mL. Under these circumstances, rapid evaluation of the surgical emergency is required to treat post-tonsillectomy hemorrhage, the most common serious complication of tonsillectomy. 

What is TXA?

For a subset of drugs, there can be a revival and repurposing as we discover new applications and uses. Having spent any time in an emergency room or around a trauma patient, you may have administered TXA (Tranexamic acid), an indirect or antifibrinolytic inhibitor, released from Shosuke Okamoto’s lab in the 1960s.  

Though other medical applications exist, first case applications of TXA involved women with heavy menstrual blood loss and patients with hereditary bleeding disorders. Since discovery, TXA has found a host of new therapeutic uses.

How Does an Antifibrionlytic Work?

Within human pathophysiology, an antifibrinolytic drug inhibits fibrinolysis by blocking the activation of proenzyme plasminogen. In short, they are a class of drugs that help the blood clot. Current antifibrinolytic agents include Amicar, Aminocaproic acid, Aprotinin, Cyklokapron, Fibrinogen, human, Fibryga, Lysteda, Riastap, Tranexamic acid and Trasylol. 

First Approval of TXA?

First approved by the FDA in 1986 as a short course injection (2-8 days), TXA intravenous (IV) solution and oral tablets prevented bleeding in hemophilia patients during tooth extraction.  

What does TXA do? In four words, TXA reduces blood loss. In trauma, the indications for TXA are in patients with massive bleeding. 

Secondary to the initial trauma, associated trauma-induced coagulopathies (TIC) cause significant mortality. Data from the international 2010 CRASH-2 (Clinical Randomization of an Antifibrinolytic in Significant Hemorrhage) involving over 20,000 patients showed survival after TXA administration increased when compared to placebo.

The CRASH-2 trial evaluated TXA effects with early administration in trauma and vascular occlusive events. In contrast to early data from CRASH-1, the CRASH-3 trial found that TXA reduced head injury death in patients with TBI.

To reduce death, TXA administration should occur within 3h of injury.  

TXA Trauma Protocol:  

• Administer within 3 hours of injury 
• Within the activation of MTP (massive transfusion protocol)  
• Systolic blood pressure < 90mmHg 

Contraindications:  

• Known hypersensitivity to tranexamic acid   
• History of severe renal failure  
• History of thromboembolism  
• Do not give with PCC (Prothrombin complex concentrates) 

Adverse Effects: 

• Anaphylaxis  
• Thrombosis  
• Hypotension (with rapid infusion, with rate > 100mg/min)  
• Nausea, vomiting, diarrhea  
• Visual Changes; blurred, color 
  

Dosing

TXA administration requires an infusion pump. The standard loading bolus dose is one gram over 10 minutes (Supplied in vials of 1gram / 10 ml). Standard IV infusion dose is one gram (added to 250cc) over 8 hours. In non-traumatic use cases, TXA administration includes oral, intravenous, topical, nebulized or as mouthwash.  

Can We Use TXA for Any Hemorrhage or Bleeding?

There are applications for TXA in bleeding aside from traumatic injury. TXA has shown to reduce bleeding in patients having cardiac surgery, epistaxis, dental extraction, gynecological surgeries, orthopedic surgeries, liver and kidney surgeries, oral and maxillofacial surgeries, dermatologic procedures and nebulization in post-tonsillectomy hemorrhage. There was no mortality changes in lower gastrointestinal bleeding.  

Providers should avoid TXA in urinary tract bleeding, secondary to the potential of intrarenal clot formation. The CRASH-1 trial data showed that after three hours, treatment was likely to be ineffective, but the CRASH-2 study showed that TXA administered to bleeding trauma patients within 8H of injury reduced death secondary to bleeding. 

Postpartum hemorrhage is the leading cause of maternal mortality in the world, accounting for over 100,000 deaths every year. Evidence suggests that TXA reduces postpartum bleeding demonstrated in the WOMAN Trial (World Maternal Antifibrinolytic Trial) in which TXA administration reduced maternal bleeding deaths by one third.

The Bottom Line

TXA reduces mortality in hemorrhaging patients by one-third when given within 3 hours regardless of the baseline risk and injury. 

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