Antifibrinolytics are medicines that promote blood clotting by preventing or slowing down a process called fibrinolysis, which is the break down of blood clots. Antifibrinolytics are used as a treatment for hemophilia, in surgical procedures to prevent excessive blood loss, and for heavy menstrual bleeding.

How antifibrinolytics work

Hemostasis is a complex physiological process that helps stop bleeding at the site of injury while maintaining normal blood circulation. An important part of this process is fibrinolysis, which regulates the formation of blood clots by a protein called fibrin. Fibrinolysis ensures excess clots are not formed that may result in inflammation or impaired blood clotting known as coagulopathy.

In diseases such as hemophilia, there is a deficiency of clotting factors in the blood that can lead to excess blood loss in case of injuries. Clotting factors interact with each other and with thrombin to convert inactive fibrinogen to fibrin that helps in forming the clot. Antifibrinolytics work by preventing the breakdown of this clot that is formed by the already limited quantities of clotting factors.

Antifibrinolytics work at different steps in the clotting process and the exact mechanism of action varies from one antifibrinolytic to another.

Common antifibrinolytics used for hemophilia

Commonly used U.S. Food and Drug Administration (FDA)-approved antifibrinolytics include aprotinin, tranexamic acid, and aminocaproic acid.

Aprotinin

Aprotinin, sold under the brand name Trasylol, is a protein inhibitor derived from bovine lung or pancreas that inhibits a class of proteins called serine proteases. Aprotinin prevents fibrinolysis by reversibly inhibiting the activity of kallikrein, a protein involved in the blood clotting pathway, thereby preventing the activation of downstream fibrinolytic processes.

Aprotinin is associated with a risk of kidney dysfunction and was removed from the worldwide market in October 2007 following the results of a clinical trial (ISRCTN15166455). However, the European Medicines Agency and Health Canada allowed Bayer, the manufacturer of Trasylol, in 2012 to market the drug in Europe and Canada after determining that the findings of the above trial were flawed.

Tranexamic acid

Tranexamic acid, sold under the brand name Cyklokapron, is derived from the amino acid lysine (amino acids are building blocks of proteins). It is used as an antifibrinolytic for hemophilia as well as for the treatment of heavy menstrual bleeding under the brand name Lysteda. Tranexamic acid binds to plasminogen in the blood clotting pathway and prevents it from interacting with fibrin, thereby stabilizing the clot and preventing blood loss.

Cyklokapron received FDA approval for use as an antifibrinolytic for hemophilia in 1999.

Aminocaproic acid

Aminocaproic acid, sold under the brand name Amicar, is another lysine derivative that inhibits plasminogen activation in the clotting process by competing with certain proteins called plasminogen activators and preventing the degradation of fibrin clots. Aminocaproic acid can also directly interact with plasmin at higher doses. It is frequently used to control bleeding during heart surgery and in the treatment of hemophilia and severe thrombocytopenia (platelet deficiency).

The use of Amicar as an antifibrinolytic was approved by the FDA in 1998. In 2018, the FDA also granted approval of a generic equivalent to Amicar that’s produced by Vitruvias Therapeutics and Sunny Pharmtech.

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