Tranexamic acid (TXA) is a medication used to treat or prevent excessive
blood loss
Bleeding, hemorrhage, haemorrhage or blood loss, is blood escaping from the circulatory system from damaged blood vessels. Bleeding can occur internally, or externally either through a natural opening such as the mouth, nose, ear, urethra, vag ...
from
major trauma
Major trauma is any injury that has the potential to cause prolonged disability or death. There are many causes of major trauma, blunt and penetrating, including falls, motor vehicle collisions, stabbing wounds, and gunshot wounds. Dependin ...
,
postpartum bleeding
Postpartum bleeding or postpartum hemorrhage (PPH) is often defined as the loss of more than 500 ml or 1,000 ml of blood following childbirth. Some have added the requirement that there also be signs or symptoms of low blood volume fo ...
, surgery,
tooth removal,
nosebleed
A nosebleed, also known as epistaxis, is bleeding from the nose. Blood can flow down into the stomach, and cause nausea and vomiting. In more severe cases, blood may come out of both nostrils. Rarely, bleeding may be so significant that low bloo ...
s, and
heavy menstruation.
It is also used for hereditary angioedema
Hereditary angioedema (HAE) is a disorder that results in recurrent attacks of severe swelling. The swelling most commonly affects the arms, legs, face, intestinal tract, and airway. If the intestinal tract is affected, abdominal pain and vomitin ...
.[ It is taken either orally or by ]injection into a vein
Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutri ...
.
Mechanism of action
Tranexamic acid is a synthetic analog
Analog or analogue may refer to:
Computing and electronics
* Analog signal, in which information is encoded in a continuous variable
** Analog device, an apparatus that operates on analog signals
*** Analog electronics, circuits which use analog ...
of the amino acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...
lysine
Lysine (symbol Lys or K) is an α-amino acid that is a precursor to many proteins. It contains an α-amino group (which is in the protonated form under biological conditions), an α-carboxylic acid group (which is in the deprotonated −C ...
. It serves as an antifibrinolytic Antifibrinolytics are a class of medication that are inhibitors of fibrinolysis. Examples include aminocaproic acid (ε-aminocaproic acid) and tranexamic acid
Tranexamic acid (TXA) is a medication used to treat or prevent excessive blood loss fr ...
by reversibly binding four to five lysine receptor sites on plasmin
Plasmin is an important enzyme () present in blood that degrades many blood plasma proteins, including fibrin clots. The degradation of fibrin is termed fibrinolysis. In humans, the plasmin protein (in the zymogen form of plasminogen) is encode ...
ogen. This decreases the conversion of plasminogen to plasmin, preventing fibrin
Fibrin (also called Factor Ia) is a fibrous, non-globular protein involved in the clotting of blood. It is formed by the action of the protease thrombin on fibrinogen, which causes it to polymerize. The polymerized fibrin, together with platele ...
degradation and preserving the framework of fibrin's matrix structure. Tranexamic acid has roughly eight times the antifibrinolytic activity of an older analogue, ε-aminocaproic acid. Tranexamic acid also directly inhibits the activity of plasmin with weak potency ( IC50 = 87 mM), and it can block the active-site of urokinase plasminogen activator
Urokinase, also known as urokinase-type plasminogen activator (uPA), is a serine protease present in humans and other animals. The human urokinase protein was discovered, but not named, by McFarlane and Pilling in 1947. Urokinase was originally i ...
(uPA) with high specificity ( Ki = 2 mM), one of the highest among all the serine proteases
Serine proteases (or serine endopeptidases) are enzymes that cleave peptide bonds in proteins. Serine serves as the nucleophilic amino acid at the (enzyme's) active site.
They are found ubiquitously in both eukaryotes and prokaryotes. Serin ...
.
Side effects are rare. Some include changes in color vision
Color vision, a feature of visual perception, is an ability to perceive differences between light composed of different wavelengths (i.e., different spectral power distributions) independently of light intensity. Color perception is a part of ...
, blood clots
A thrombus (plural thrombi), colloquially called a blood clot, is the final product of the blood coagulation step in hemostasis. There are two components to a thrombus: aggregated platelets and red blood cells that form a plug, and a mesh of cr ...
, and allergic reaction
Allergies, also known as allergic diseases, refer a number of conditions caused by the hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include hay fever, food allergies, atopic derma ...
s.[ Greater caution is recommended in people with kidney disease.][ Tranexamic acid appears to be safe for use during pregnancy and breastfeeding.][ Tranexamic acid is an ]antifibrinolytic Antifibrinolytics are a class of medication that are inhibitors of fibrinolysis. Examples include aminocaproic acid (ε-aminocaproic acid) and tranexamic acid
Tranexamic acid (TXA) is a medication used to treat or prevent excessive blood loss fr ...
medication.
Tranexamic acid was first made in 1962 by Japanese researchers Shosuke and Utako Okamoto
was a Japanese medical doctor working as a medical scientist who discovered tranexamic acid in the 1950s in her quest to find a drug that would treat bleeding after childbirth ( post-partum haemorrhage). After publishing results in 1962 she bec ...
. It is on the World Health Organization's List of Essential Medicines
The WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health ...
. Tranexamic acid is available as a generic drug
A generic drug is a pharmaceutical drug that contains the same chemical substance as a drug that was originally protected by chemical patents. Generic drugs are allowed for sale after the patents on the original drugs expire. Because the active ch ...
.
Medical uses
Tranexamic acid is frequently used following major trauma. 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.
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
Trauma most often refers to:
* Major trauma, in physical medicine, severe physical injury caused by an external source
* Psychological trauma, a type of damage to the psyche that occurs as a result of a severely distressing event
*Traumatic i ...
. It is most effective if taken within the first three hours following major trauma. It also decreases the risk of death if given within the first three hours of brain injury.
Menstrual bleeding
Tranexamic acid is sometimes used to treat heavy menstrual bleeding. When taken by mouth it both safely and effectively treats regularly occurring heavy menstrual bleeding and improves quality of life. Another study demonstrated that the dose does not need to be adjusted in females who are between ages 12 and 16.
Childbirth
Tranexamic acid is sometimes used (often in conjunction with oxytocin
Oxytocin (Oxt or OT) is a peptide hormone and neuropeptide normally produced in the hypothalamus and released by the posterior pituitary. It plays a role in social bonding, reproduction, childbirth, and the period after childbirth. Oxytocin ...
) to reduce bleeding after childbirth. Death due to postpartum bleeding
Postpartum bleeding or postpartum hemorrhage (PPH) is often defined as the loss of more than 500 ml or 1,000 ml of blood following childbirth. Some have added the requirement that there also be signs or symptoms of low blood volume fo ...
is reduced in women receiving tranexamic acid.
Surgery
* Tranexamic acid is sometimes used in orthopedic surgery
Orthopedic surgery or orthopedics ( alternatively spelt orthopaedics), is the branch of surgery concerned with conditions involving the musculoskeletal system. Orthopedic surgeons use both surgical and nonsurgical means to treat musculoskeletal ...
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.
* In surgical corrections of craniosynostosis
Craniosynostosis is a condition in which one or more of the fibrous sutures in a young infant's skull prematurely fuses by turning into bone (ossification), thereby changing the growth pattern of the skull. Because the skull cannot expand perpe ...
in children it reduces the need for blood transfusions.
* In spinal surgery (e.g., scoliosis
Scoliosis is a condition in which a person's spine has a sideways curve. The curve is usually "S"- or "C"-shaped over three dimensions. In some, the degree of curve is stable, while in others, it increases over time. Mild scoliosis does not t ...
), correction with posterior spinal fusion using instrumentation, to prevent excessive blood loss.
* In cardiac surgery
Cardiac surgery, or cardiovascular surgery, is surgery on the heart or great vessels performed by cardiac surgeons. It is often used to treat complications of ischemic heart disease (for example, with coronary artery bypass grafting); to corr ...
, both with and without cardiopulmonary bypass
Cardiopulmonary bypass (CPB) is a technique in which a machine temporarily takes over the function of the heart and lungs during surgery, maintaining the circulation of blood and oxygen to the body. The CPB pump itself is often referred to as a he ...
(e.g., coronary artery bypass surgery
Coronary artery bypass surgery, also known as coronary artery bypass graft (CABG, pronounced "cabbage") is a surgical procedure to treat coronary artery disease (CAD), the buildup of plaques in the arteries of the heart. It can relieve chest pai ...
), it is used to prevent excessive blood loss.
Dentistry
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. 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.
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.
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. 0.05% TXA in toothpaste is allowed OTC in Hong Kong. <5% TXA in over-the-counter toothpaste is first patented and marketed by Lion Corporation
is a Japanese multinational manufacturer of detergent, soap, medications, and oral hygiene products and other toiletries. The company also has a chemical engineering
Chemical engineering is an engineering field which deals with the study o ...
in Japan, where it is still sold. Presence of unauthorized TXA has led to the Canadian recall of a Yunnan Baiyao
Yunnan Baiyao (or Yunnan Paiyao; ) is a proprietary traditional Chinese medicine marketed and used as a Antihemorrhagic, hemostatic product in both human and veterinary alternative medicine. Although Yunnan Baiyao has long been recognized as a ph ...
toothpaste in 2019.
Hematology
There is not enough evidence to support the routine use of tranexamic acid to prevent bleeding in people with blood cancers. However, there are several trials that are currently assessing this use of tranexamic acid. For people with inherited bleeding disorders (e.g. von Willebrand's disease
Von Willebrand disease (VWD) is the most common hereditary blood-clotting disorder in humans. An acquired form can sometimes result from other medical conditions. It arises from a deficiency in the quality or quantity of von Willebrand factor ...
), tranexamic acid is often given. It has also been recommended for people with acquired bleeding disorders (e.g., directly acting oral anticoagulant
Anticoagulants, commonly known as blood thinners, are chemical substances that prevent or reduce coagulation of blood, prolonging the clotting time. Some of them occur naturally in hematophagy, blood-eating animals such as leeches and mosquitoes, ...
s (DOACs)) to treat serious bleeding.
Nosebleeds
The use of tranexamic acid, applied directly to the area that is bleeding or taken by mouth, appears useful to treat nose bleeding
A nosebleed, also known as epistaxis, is bleeding from the nose. Blood can flow down into the stomach, and cause nausea and vomiting. In more severe cases, blood may come out of both nostrils. Rarely, bleeding may be so significant that low bloo ...
compared to packing the nose with cotton pledgets alone. It decreases the risk of rebleeding within 10 days.
Other uses
* Tentative evidence supports the use of tranexamic acid in hemoptysis
Hemoptysis is the coughing up of blood or blood-stained mucus from the bronchi, larynx, trachea, or lungs. In other words, it is the airway bleeding. This can occur with lung cancer, infections such as tuberculosis, bronchitis, or pneumonia, and ...
.
* In hereditary angioedema
Hereditary angioedema (HAE) is a disorder that results in recurrent attacks of severe swelling. The swelling most commonly affects the arms, legs, face, intestinal tract, and airway. If the intestinal tract is affected, abdominal pain and vomitin ...
* In hereditary hemorrhagic telangiectasia
Hereditary hemorrhagic telangiectasia (HHT), also known as Osler–Weber–Rendu disease and Osler–Weber–Rendu syndrome, is a rare autosomal dominant genetic disorder that leads to abnormal blood vessel formation in the skin, mucous membranes, ...
- Tranexamic acid has been shown to reduce frequency of epistaxis
A nosebleed, also known as epistaxis, is bleeding from the nose. Blood can flow down into the stomach, and cause nausea and vomiting. In more severe cases, blood may come out of both nostrils. Rarely, bleeding may be so significant that low bloo ...
in patients with severe and frequent nosebleed episodes from hereditary hemorrhagic telangiectasia.
* In melasma
Melasma (also known as chloasma faciei,James, William; Berger, Timothy; Elston, Dirk (2005). ''Andrews' Diseases of the Skin: Clinical Dermatology''. (10th ed.). Saunders. . or the mask of pregnancy when present in pregnant women) is a tan or dark ...
- 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. It is allowed as a quasi-drug
Cosmeceuticals are cosmetic products with bioactive ingredients purported to have medical benefits. In America, there are no legal requirements to prove that these products live up to their claims. The name is a portmanteau of "cosmetics" and " ...
for skin whitening in Japan.
* In hyphema
Hyphema is a condition that occurs when blood enters the front (anterior) chamber of the eye between the iris and the cornea. People usually first notice a loss of vision or decrease in vision. The eye may also appear to have a reddish tinge, o ...
- Tranexamic acid has been shown to be effective in reducing risk of secondary hemorrhage outcomes in people with traumatic hyphema.
Experimental uses
Tranexamic acid might alleviate neuroinflammation
Neuroinflammation is inflammation of the nervous tissue. It may be initiated in response to a variety of cues, including infection, traumatic brain injury,Ebert SE, Jensen P, Ozenne B, Armand S, Svarer C, Stenbaek DS ''et al.'' Molecular imaging of ...
in some experimental settings.
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.
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
Adverse effects
Side effects are rare.[ Some reported adverse events include changes in ]color vision
Color vision, a feature of visual perception, is an ability to perceive differences between light composed of different wavelengths (i.e., different spectral power distributions) independently of light intensity. Color perception is a part of ...
, blood clot
A thrombus (plural thrombi), colloquially called a blood clot, is the final product of the blood coagulation step in hemostasis. There are two components to a thrombus: aggregated platelets and red blood cells that form a plug, and a mesh of ...
s, and allergic reaction
Allergies, also known as allergic diseases, refer a number of conditions caused by the hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include hay fever, food allergies, atopic derma ...
s such as anaphylaxis
Anaphylaxis is a serious, potentially fatal allergic reaction and medical emergency that is rapid in onset and requires immediate medical attention regardless of use of emergency medication on site. It typically causes more than one of the follow ...
.[ Whether the risk of ]venous thromboembolism
Venous thrombosis is blockage of a vein caused by a thrombus (blood clot). A common form of venous thrombosis is deep vein thrombosis (DVT), when a blood clot forms in the deep veins. If a thrombus breaks off (embolizes) and flows to the lungs to ...
(blood clots) is actually increased is a matter of debate. The risk is mentioned in the product literature, and they were reported in post marketing experience. 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, even in people who had previously experienced thrombosis under other circumstances.[
]
Special populations
* Tranexamic acid is categorized as pregnancy category
The pregnancy category of a medication is an assessment of the risk of fetal injury due to the pharmaceutical, if it is used as directed by the mother during pregnancy. It does ''not'' include any risks conferred by pharmaceutical agents or their ...
B. No harm has been found in animal studies.
* Small amounts appear in breast milk if taken during lactation. If it is required for other reasons, breastfeeding may be continued.
* 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.
* In liver impairment, dose change is not needed as only a small amount of the drug is metabolized through the liver.
Society and culture
Tranexamic acid was first synthesized in 1962 by Japanese researchers Shosuke and Utako Okamoto
was a Japanese medical doctor working as a medical scientist who discovered tranexamic acid in the 1950s in her quest to find a drug that would treat bleeding after childbirth ( post-partum haemorrhage). After publishing results in 1962 she bec ...
.[ It has been included in the ]WHO list of essential medicines
Essential medicines, as defined by the World Health Organization (WHO), are the medicines that "satisfy the priority health care needs of the population". These are the medications to which people should have access at all times in sufficient ...
.
Brand names
Tranexamic acid is marketed in the U.S. and Australia in tablet form as Lysteda and in Australia, Sweden and Jordan it is marketed in an IV form and tablet form as Cyklokapron, in the UK and Sweden 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.
Approval
The U.S. Food and Drug Administration (FDA) approved tranexamic acid oral tablets (brand name Lysteda) for treatment of heavy menstrual bleeding on 13 November 2009.
In March 2011 the status of tranexamic acid for treatment of heavy menstrual bleeding
Heavy menstrual bleeding (HMB), previously known as menorrhagia or hypermenorrhea, is a menstrual period with excessively heavy flow. It is a type of abnormal uterine bleeding (AUB).
Abnormal uterine bleeding can be caused by structural abnorma ...
was changed in the UK, from PoM (Prescription only Medicines) to P (Pharmacy Medicines) and became available over the counter
Over-the-counter (OTC) drugs are medicines sold directly to a consumer without a requirement for a prescription from a healthcare professional, as opposed to prescription drugs, which may be supplied only to consumers possessing a valid prescr ...
in UK pharmacies under the brand names of Cyklo-F and Femstrual, initially exclusively for Boots pharmacy, which has sparked some discussion about availability. (In parts of Europe it had then been available OTC for over a decade.) Regular liver function tests
Liver function tests (LFTs or LFs), also referred to as a hepatic panel, are groups of blood tests that provide information about the state of a patient's liver. These tests include prothrombin time (PT/INR), activated partial thromboplastin ti ...
are recommended when using tranexamic acid over a long period of time.
References
External links
ISBT information on tranexamic acid
Tranexamic acid
UK patient information leaflet
CRASH-2: tranexamic acid and trauma patients
TXA central
site collating all clinical evidence for tranexamic acid by the London School of Hygiene & Tropical Medicine
The London School of Hygiene and Tropical Medicine (LSHTM) is a public research university in Bloomsbury, central London, and a member institution of the University of London that specialises in public health and tropical medicine.
The inst ...
*
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