Tranexamic acid (TXA)

Tranexamic acid, often shortened to TXA, is a synthetic compound used for various medical purposes. It is primarily used as an agent to clot blood. Clotting, or coagulation, is the process that blood undergoes when a blood vessel is damaged and blood escapes. Blood cells trigger the reaction, which creates a swelling that prevents more blood from escaping until the vessel heals. Exposed human blood will naturally start to clot in most situations, but in cases of heavy bleeding, it may not be able to clot quickly enough, and the excessive blood loss can have dangerous effects. TXA can be used to minimize the threat in these situations. It promotes blood's clotting tendency, helping users recover from surgery, transfusions, menstrual periods, or pregnancies. TXA is readily available in most nations and is relatively affordable. Its side effects are typically rare and mild.

Background

Japanese doctor Utako Okamoto was researching blood with her husband at Keio University in the late 1940s. In the 1950s, she was seeking a method to combat bleeding that occurred during and after childbirth. She found encouraging results with a certain type of amino acid, called epsilon-aminocaproic acid, or EACA. Studying that led her to discover a similar acid that could be created synthetically. Her findings revealed that what would become known as tranexamic acid was many times more potent than EACA. It was especially useful during pregnancies because it appeared to pose no risk to the unborn or recently born baby.

She released the first medical publication describing TXA in the Keio Journal of Medicine in 1962. It underwent its first clinical trials afterward, and the results were published in 1968. Those trials helped establish TXA as a treatment for menstrual bleeding.

Okamoto battled sexism throughout her career, and the medical community at large did not grasp TXA's potential for decades. It gained the interest of more researchers in the late twentieth century, and an increasing number of medical publications began recommending it for a variety of different scenarios. Surgeons in particular developed a great deal of respect for how it reduced the risks of many different types of operations. In 2009, the World Health Organization included TXA in its list of essential medicines. That same year, the US Food and Drug Administration approved TXA tablets as a method for controlling bleeding during menstrual periods.

2010 saw TXA put through very intensive studies and trials that made its benefits well known on a global scale. One of the studies was known as a CRASH-2 trial. It was an international study with a large sample size, consisting of more than 20,000 patients in 274 hospitals across 40 different countries. Another study was called the WOMAN trial, an acronym for World Maternal Antifibrinolytic. This took place over several years and involved more than 20,000 women with postpartum hemorrhage. It was a double-blind study in which some women were treated with TXA and others with placebos (drugs that had no effect). TXA proved noticeably useful for treating the bleeding without causing any negative side effects.

Overview

TXA attacks a process known as fibrinolysis, which causes blood clots to decay and dissolve. Primary fibrinolysis occurs naturally, as a blood clot can interfere with typical bodily functions. Secondary fibrinolysis is caused by an outside source. This source can be certain forms of disease, or a medication prescribed when a patient is at risk of stroke or otherwise needs to prevent clotting. With most injuries, primary fibrinolysis balances naturally with clotting. But when severe bleeding occurs, the body is unable to keep up, which can cause excessive fibrinolysis. TXA works by replacing fibrin, binding with the enzyme that fibrin would normally bind with to break down clots, which delays that process and allows clots to form and remain intact.

TXA is typically taken in the form of tablets, which are swallowed. Patients can also receive injections of the acid. It remains active for about three hours, and is then expelled from the body as waste.

Following the success of the CRASH-2 trial, other major groups have moved to study TXA. The military began a study called the Military Application of Tranexamic Acid in Trauma Emergency Resuscitation, or MATTERs. It was designed to test the effectiveness of TXA at healing combat injuries and reducing battlefield mortalities. It also applied to combatants who were receiving emergency transfusions. TXA proved extremely useful at reducing fatalities due to blood loss, and demonstrated that it could help the military carry out transfusions with lower risk, even in conditions that were not ideal.

TXA's side effects have been rare, but they include pain in the back, stomach, joints, bones, or muscles. Headaches and fatigue have also been reported. The drug can also cause complications if misused. Ordinarily, blood clots are dissolved by fibrin a short time after they form. If TXA is used for minor bleeding, the clot may persist longer than it should, blocking blood flow. When blood is prevented from circulating through extremities, it can cause swelling, pain, and weakness. If inadequate blood is flowing to the brain, it can cause problems with speech and sight, as well as seizures. It can also cause severe chest pains and difficulty breathing or exerting oneself if it fails to reach the lungs or heart. For this reason, TXA should only be used in cases of very heavy bleeding.

Since TXA's effects are time sensitive, it is most useful when the time of bleeding can be predicted. This is why it is most frequently used for medical procedures or menstrual periods. However, if it is available, it can prevent people from bleeding out due to wounds. Because of its versatility, potency, and low cost, TXA is used in a wide range of places and situations.

Bibliography

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