Tranexamic acid
Encyclopedia
Tranexamic acid is a drug used to treat or prevent excessive blood loss during surgery and in certain other conditions. It is an antifibrinolytic
that competitively inhibits the activation of plasminogen to plasmin
, a molecule responsible for the degradation of fibrin
, a protein that forms the framework of blood clots. It has roughly 8 times the antifibrinolytic
activity of an older analogue, ε-aminocaproic acid
.
.
. It exerts its antifibrinolytic effect through the reversible blockade of lysine-binding sites on plasminogen molecules. It inhibits endometrial (or endothelial) plasminogen activator and thus prevents fibrinolysis and the breakdown of blood clots. Side effects are uncommon. While prolonged treatment may heighten the risk of an increased thrombotic tendency, such as deep vein thrombosis, large scale studies reveal the incidence of thrombosis in women treated by tranexamic acid is no different from the spontaneous incidence of thrombosis in untreated women. Tranexamic acid is used as firstline nonhormonal treatment of dysfunctional uterine bleeding, and heavy bleeding associated with uterine fibroids. A recent study showed patients treated with tranexamic acid are more likely to develop thrombosis and necrosis in their fibroids, and may result in pain and fever. Moreover, the histological appearance of the necrosis in women treated by tranexamic acid is no different from the spontaneous incidence of thrombosis. 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 was changed in the UK, from PoM (Prescription only Medicines) to P (Pharmacy Medicines) and became available over the counter in UK pharmacies under the brand names of Cyclo-F and Femstrual, initially exclusively for Boots pharmacy, which has sparked some discussion about availability . (In parts of Europe - like for example Sweden - it had then been available OTC for over a decade.)
Antifibrinolytic
Antifibrinolytics, such as aminocaproic acid and tranexamic acid are used as inhibitors of fibrinolysis. These lysine-like drugs interfere with the formation of the fibrinolytic enzyme plasmin from its precursor plasminogen by plasminogen activators which takes place mainly in lysine rich areas...
that competitively inhibits the activation of plasminogen to plasmin
Plasmin
Plasmin is an important enzyme present in blood that degrades many blood plasma proteins, most notably, fibrin clots. The degradation of fibrin is termed fibrinolysis. In humans, the plasmin protein is encoded by the PLG gene.- Function :...
, a molecule responsible for the degradation of fibrin
Fibrin
Fibrin is a fibrous, non-globular protein involved in the clotting of blood. It is a fibrillar protein that is polymerised to form a "mesh" that forms a hemostatic plug or clot over a wound site....
, a protein that forms the framework of blood clots. It has roughly 8 times the antifibrinolytic
Antifibrinolytic
Antifibrinolytics, such as aminocaproic acid and tranexamic acid are used as inhibitors of fibrinolysis. These lysine-like drugs interfere with the formation of the fibrinolytic enzyme plasmin from its precursor plasminogen by plasminogen activators which takes place mainly in lysine rich areas...
activity of an older analogue, ε-aminocaproic acid
Aminocaproic acid
Aminocaproic acid is a derivative and analogue of the amino acid lysine, which makes it an effective inhibitor for enzymes that bind that particular residue. Such enzymes include proteolytic enzymes like plasmin, the enzyme responsible for fibrinolysis...
.
Medical uses
Tranexamic acid is frequently used in surgeries with high risk of blood loss such as cardiac, liver, vascular and large orthopedic procedures. Its oral form is now being evaluated for use in outpatient conditions involving heavy bleeding.Trauma
Tranexamic acid has been found to decrease the risk of death in people who have significant bleeding due to trauma.Heart surgery
Tranexamic acid is commonly used in cardiac surgery, both with and without Cardiopulmonary Bypass. It replaces aprotininAprotinin
The drug aprotinin , is the bovine version of the small protein basic pancreatic trypsin inhibitor, or BPTI, which inhibits trypsin and related proteolytic enzymes. Under the trade name Trasylol, aprotinin was used as a medication administered by injection to reduce bleeding during complex surgery,...
.
Orthopedic surgery
Tranexamic acid is used in orthopedic surgery to reduce bloodloss. It is of proven value in clearing the field of surgery and reducing pre- and postoperative blood loss. Drain and number of transfusions are reduced. However, the hidden blood loss is not reduced. Still, it is becoming an important tool in the anaesthetist's arsenal. It is commonly used in joint replacement surgery.Menstrual bleeding
Tranexamic acid is a synthetic derivative of the amino acid lysineLysine
Lysine is an α-amino acid with the chemical formula HO2CCH4NH2. It is an essential amino acid, which means that the human body cannot synthesize it. Its codons are AAA and AAG....
. It exerts its antifibrinolytic effect through the reversible blockade of lysine-binding sites on plasminogen molecules. It inhibits endometrial (or endothelial) plasminogen activator and thus prevents fibrinolysis and the breakdown of blood clots. Side effects are uncommon. While prolonged treatment may heighten the risk of an increased thrombotic tendency, such as deep vein thrombosis, large scale studies reveal the incidence of thrombosis in women treated by tranexamic acid is no different from the spontaneous incidence of thrombosis in untreated women. Tranexamic acid is used as firstline nonhormonal treatment of dysfunctional uterine bleeding, and heavy bleeding associated with uterine fibroids. A recent study showed patients treated with tranexamic acid are more likely to develop thrombosis and necrosis in their fibroids, and may result in pain and fever. Moreover, the histological appearance of the necrosis in women treated by tranexamic acid is no different from the spontaneous incidence of thrombosis. 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 was changed in the UK, from PoM (Prescription only Medicines) to P (Pharmacy Medicines) and became available over the counter in UK pharmacies under the brand names of Cyclo-F and Femstrual, initially exclusively for Boots pharmacy, which has sparked some discussion about availability . (In parts of Europe - like for example Sweden - it had then been available OTC for over a decade.)
Dentistry
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.Other uses
- In obstetrics, tranexamic acid is used after delivery to reduce bleeding, often with syntocinon/oxytocin and fundal massage. A major trial is in progress in Nigeria to establish the efficacy of the drug to arrest postpartum haemorrhage (PPH). Since the drug can be administered orally, it has great potential to reduce maternal mortality rates in developing countries where primary healthcare is often unavailable.
- In cardiac surgeryCardiac surgeryCardiovascular surgery is surgery on the heart or great vessels performed by cardiac surgeons. Frequently, it is done to treat complications of ischemic heart disease , correct congenital heart disease, or treat valvular heart disease from various causes including endocarditis, rheumatic heart...
, e.g. coronary artery bypass surgeryCoronary artery bypass surgeryCoronary artery bypass surgery, also coronary artery bypass graft surgery, and colloquially heart bypass or bypass surgery is a surgical procedure performed to relieve angina and reduce the risk of death from coronary artery disease...
, it is used to prevent excessive blood loss. - In hemophilia - Tranexamic acid is also useful in the treatment of bleeding as a second line treatment after factor VIII in patients (e.g. tooth extraction).
- In hereditary angioedemaHereditary angioedemaHereditary angioedema presents in the second to fourth decade, and is characterized by local swelling in subcutaneous tissues....
External links
- http://www.chemistanddruggist.co.uk/news-content/-/article_display_list/4544044/4544040 (PoM to P in the UK)
- http://dotpharmacy.cmpi.biz/c/portal/layout?p_l_id=259751&CMPI_SHARED_articleId=4577833&CMPI_SHARED_ImageArticleId=4577833&CMPI_SHARED_CommentArticleId=4577833&CMPI_SHARED_ToolsArticleId=4577833&CMPI_SHARED_articleIdRelated=4577833 (Exclusivity controversy)
- http://www.thelancet.com/crash-2 (Final results from the Crash2 study)
- Patient Experience with Tranexamic Acid (Patient Experience)
- Tranexamic acid (Dr. P.L.F. Giangrande, Oxford Haemophilia Centre)
- Tranexamic acid (UK patient information leaflet)
- Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial (The Lancet)
- Drug will save lives of accident victims, says study (BBC News article)
- Types of Angioedema and treatments (Hereditary Angioedema Association)