Antifibrinolytics

Dr Amanda Quarshie
Introduction
• Fibrinolysis is a physiological component of hemostasis whose
function is to limit clot formation
• However after surgery or trauma excessive fibrinolysis may contribute
to coagulopathy, bleeding and inflammatory responses
• Antifibrinolytic agents are increasingly being used to reduce bleeding,
blood transfusion and adverse clinical outcomes
Introduction
• Fibrinolysis regulates the extent fibrin formation and vascular
obstruction during Hemostasis
• After tissue and vascular injury, hemostatic mechanisms are activated
that result in platelet adhesion, crosslinking of platelets and fibrin
formation
• Fibrinolysis is initiated as part of the hemostatic response
• Fibrin, the end product of coagulation becomes the cofactor for
plasminogen to be activated to tissue plasminogen activator
• Plasmin then lyses fibrin
Introduction
• Plasmin also mediates inactivation of many hemostatic and
inflammatory components which are more in concentration than local
and systemic inhibitors eg alpha –antiplasmin
• It also cleaves glycoprotein Ib and IIb/IIIa receptors on platelets,
reducing platelet adhesion and aggregation
• Plasmin is activated by tissue plasmin activator as well as urokinase-
plasmin activator
• Plasmin binds to lysine residues in fibrin to achieve fibrinolysis
Pharmacology of antifibrinolytic agents
The two main antifibrinolytic agents are the synthetic lysine analogues
Tranexamic acid
E-aminocaproic acid
• They inhibit fibrinolysis by attaching to the lysine binding site of the
plasminogen molecule, thereby displacing plasminogen from fibrin
Aprotinin
• Another fibrinolysis inhibitor, is a broad spectrum , naturally occurring
protease inhibitor and is only available in certain countries
Aprotinin
• It is a protease inhibitor isolated from bovine lung
• Dose is measured in ‘kallikrein inhibitng units’
• The initial plasma half-life is 150 minutes, and a terminal half life of 10
hrs
• It is eliminated predominantly by proteolysis, and to a small extent by
kidneys
• It is a broad spectrum protease inhibitor that forms reversible
complexes with active serine residues in various plasma proteases
• Thus it reversibly inhibits trypsin, kallikrein, plasmin, elastase, and
• It is the most potent antifbrinolytic agent
Aprotinin
• It has however been banned from some countries because of a low
safety profile
Uses
• Prophylaxis to reduce blood loss and blood transfusion in adult
patients at risk of major blood loss
E-aminocaproic acid
• A synthetic inhibitor of plasminogen activation
• It is rapidly excreted in the urine after IV administration therefore must
administered as an infusion to maintain therapeutic concentrations
• Dose: 5g orally; IV: 5g loading dose infusion over 30 minutes, 1-1.25g/hr
till bleeding stops
Side effects
• Hypotension Abdominal discomfort
• Cardiac arrhythmias Nasal stuffiness
• Rhabdomyolysis intravascular thrombosis
• Renal dysfunction
Uses
• Overdose of thrombolytic agents eg t-PA
• Post surgical bleeding
• Haemophilia
• Prophylaxis to rebleeding in intracranial haemorrhage
• Bladder haemorrhage from radiation
• Hereditary angioneurotic oedema
Tranexamic acid
• It is a lysine analogue with a MWt of 157D
• It reversibly binds to multiple proteins including fibrin
• Tranexamic acid is also eliminated by the kidney through glomerular
filtration like aminocaproic acid
• It is 7-10X more potent than ECA, and has more sustained anti
fibrinolytic activity
• It can be given orally and IV
• Dose: Oral:1-15g 2-3x dly
• IV; 10-15mg /kg tds
Tranexamic acid
Clinical Uses
• Cardiac surgery
• Liver surgery
• Orthopedic surgery-reduces bleeding and transfusion requirements
• Postpartum haemorrhage- given immediately after vaginal delivery or before
caesarian section
• Traumatic injury
• Intracranial haemorrhage and Neurosurgery-
• Tooth extraction in haemophilia patients
• Prostate surgery
Tranexamic acid
Heavy bleeding associated with fibroids
Side effects
• DVT
• GIT distress
• Seizure with cardiac surgery
• Ocular and visual disturbance
• Hypersensitivity
• Muscle pain