Antifibrinolytic
Encyclopedia
Antifibrinolytics, such as aminocaproic acid
(ε-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 (primarily t-PA and u-PA) which takes place mainly in lysine rich areas on the surface of fibrin. These drugs block the binding sites of the enzymes or plasminogen respectively and thus stop plasmin
formation.
They are used in menorrhagia
and bleeding tendency due to various causes.
Their application may be beneficial in patients with hyperfibrinolysis because they arrest bleeding rapidly if the other components of the haemostatic system are not severely affected. This may help to avoid the use of blood products such as fresh frozen plasma
(FFP) with its associated risks of infections or anaphylactic reactions.
In 2010, the CRASH-2 trial showed that the antifibrinolytic drug tranexamic acid
safely reduces mortality in bleeding trauma patients.
The antifibrinolytic drug aprotinin
was abandoned after identification of major side effects, especially on kidney.
The indication for use of antifibrinolytic drugs is made with various methods. The most rapid and suitable one is thrombelastometry (TEM) in whole blood, which is even possible in patients on heparin
. With various assays, an enhanced fibrinolysis
becomes visible in the curve signature (TEMogram) and from the calculated values, e.g. the maximum lysis
parameter. A special test for the identification of increased fibrinolysis
(APTEM) compares the TEM in the absence or presence of the fibrinolysis inhibitor aprotinin
. In severe cases of activated fibrinolysis, this assay confirms the syndrome already in less than 15 min during the early phases of clot formation
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...
(ε-aminocaproic acid) and tranexamic acid
Tranexamic acid
Tranexamic acid is a drug used to treat or prevent excessive blood loss during surgery and in certain other conditions...
are used as inhibitors of fibrinolysis
Fibrinolysis
Fibrinolysis is a process that prevents blood clots from growing and becoming problematic. This process has two types: primary fibrinolysis and secondary fibrinolysis...
. These lysine-like drugs interfere with the formation of the fibrinolytic enzyme plasmin from its precursor plasminogen by plasminogen activators (primarily t-PA and u-PA) which takes place mainly in lysine rich areas on the surface of fibrin. These drugs block the binding sites of the enzymes or plasminogen respectively and thus stop 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 :...
formation.
They are used in menorrhagia
Menorrhagia
Menorrhagia is an abnormally heavy and prolonged menstrual period at regular intervals. Causes may be due to abnormal blood clotting, disruption of normal hormonal regulation of periods or disorders of the endometrial lining of the uterus...
and bleeding tendency due to various causes.
Their application may be beneficial in patients with hyperfibrinolysis because they arrest bleeding rapidly if the other components of the haemostatic system are not severely affected. This may help to avoid the use of blood products such as fresh frozen plasma
Fresh frozen plasma
The term fresh frozen plasma refers to the liquid portion of human blood that has been frozen and preserved after a blood donation and will be used for blood transfusion...
(FFP) with its associated risks of infections or anaphylactic reactions.
In 2010, the CRASH-2 trial showed that the antifibrinolytic drug tranexamic acid
Tranexamic acid
Tranexamic acid is a drug used to treat or prevent excessive blood loss during surgery and in certain other conditions...
safely reduces mortality in bleeding trauma patients.
The antifibrinolytic drug aprotinin
Aprotinin
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,...
was abandoned after identification of major side effects, especially on kidney.
The indication for use of antifibrinolytic drugs is made with various methods. The most rapid and suitable one is thrombelastometry (TEM) in whole blood, which is even possible in patients on heparin
Heparin
Heparin , also known as unfractionated heparin, a highly sulfated glycosaminoglycan, is widely used as an injectable anticoagulant, and has the highest negative charge density of any known biological molecule...
. With various assays, an enhanced fibrinolysis
Fibrinolysis
Fibrinolysis is a process that prevents blood clots from growing and becoming problematic. This process has two types: primary fibrinolysis and secondary fibrinolysis...
becomes visible in the curve signature (TEMogram) and from the calculated values, e.g. the maximum lysis
Lysis
Lysis refers to the breaking down of a cell, often by viral, enzymic, or osmotic mechanisms that compromise its integrity. A fluid containing the contents of lysed cells is called a "lysate"....
parameter. A special test for the identification of increased fibrinolysis
Fibrinolysis
Fibrinolysis is a process that prevents blood clots from growing and becoming problematic. This process has two types: primary fibrinolysis and secondary fibrinolysis...
(APTEM) compares the TEM in the absence or presence of the fibrinolysis inhibitor aprotinin
Aprotinin
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,...
. In severe cases of activated fibrinolysis, this assay confirms the syndrome already in less than 15 min during the early phases of clot formation